ABSTRACT
BACKGROUND: Dendrobium Sw. represents one of the most expansive genera within the Orchidaceae family, renowned for its species' high medicinal and ornamental value. In higher plants, the ankyrin (ANK) repeat protein family is characterized by a unique ANK repeat domain, integral to a plethora of biological functions and biochemical activities. The ANK gene family plays a pivotal role in various plant physiological processes, including stress responses, hormone signaling, and growth. Hence, investigating the ANK gene family and identifying disease-resistance genes in Dendrobium is of paramount importance. RESULTS: This research identified 78 ANK genes in Dendrobium officinale Kimura et Migo, 77 in Dendrobium nobile Lindl., and 58 in Dendrobium chrysotoxum Lindl. Subsequently, we conducted comprehensive bioinformatics analyses on these ANK gene families, encompassing gene classification, chromosomal localization, phylogenetic relationships, gene structure and motif characterization, cis-acting regulatory element identification, collinearity assessment, protein-protein interaction network construction, and gene expression profiling. Concurrently, three DoANK genes (DoANK14, DoANK19, and DoANK47) in D. officinale were discerned to indirectly activate the NPR1 transcription factor in the ETI system via SA, thereby modulating the expression of the antibacterial PR gene. Hormonal treatments with GA3 and ABA revealed that 17 and 8 genes were significantly up-regulated, while 4 and 8 genes were significantly down-regulated, respectively. DoANK32 was found to localize to the ArfGAP gene in the endocytosis pathway, impacting vesicle transport and the polar movement of auxin. CONCLUSION: Our findings provide a robust framework for the taxonomic classification, evolutionary analysis, and functional prediction of Dendrobium ANK genes. The three highlighted ANK genes (DoANK14, DoANK19, and DoANK47) from D. officinale may prove valuable in disease resistance and stress response research. DoANK32 is implicated in the morphogenesis and development of D. officinale through its role in vesicular transport and auxin polarity, with subcellular localization studies confirming its presence in the nucleus and cell membrane. ANK genes displaying significant expression changes in response to hormonal treatments could play a crucial role in the hormonal response of D. officinale, potentially inhibiting its growth and development through the modulation of plant hormones such as GA3 and ABA.
Subject(s)
Abscisic Acid , Dendrobium , Gibberellins , Multigene Family , Phylogeny , Plant Growth Regulators , Dendrobium/genetics , Dendrobium/drug effects , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , Gibberellins/pharmacology , Gibberellins/metabolism , Plant Growth Regulators/pharmacology , Plant Growth Regulators/metabolism , Ankyrin Repeat/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Genes, Plant , Genome, Plant , Gene Expression ProfilingABSTRACT
Jinhu groupers, the hybrid offspring of tiger groupers (Epinephelus fuscoguttatus) and potato groupers (Epinephelus tukula), have excellent heterosis in fast growth and strong stress resistance. However, compared with the maternal tiger grouper, Jinhu groupers show delayed gonadal development. To explore the interspecific difference in gonadal development, we compared the transcriptomes of brain, pituitary, and gonadal tissues between Jinhu groupers and tiger groupers at 24-months old. In total, 3034 differentially expressed genes (DEGs) were obtained. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that the osteoclast differentiation, oocyte meiosis, and ovarian steroidogenesis may be involved in the difference in gonadal development. Trend analysis showed that the DEGs were mainly related to signal transduction and cell growth and death. Additionally, differences in expression levels of nr4a1, pgr, dmrta2, tbx19, and cyp19a1 may be related to gonadal retardation in Jinhu groupers. A weighted gene co-expression network analysis revealed three modules (i.e., saddlebrown, paleturquoise, and greenyellow) that were significantly related to gonadal development in the brain, pituitary, and gonadal tissues, respectively, of Jinhu groupers and tiger groupers. Network diagrams of the target modules were constructed and the respective hub genes were determined (i.e., cdh6, col18a1, and hat1). This study provides additional insight into the molecular mechanism underlying ovarian stunting in grouper hybrids.
Subject(s)
Bass , Transcriptome , Animals , Female , Transcriptome/genetics , Bass/genetics , Bass/growth & development , Bass/metabolism , Male , Gene Expression Profiling/methods , Hypothalamo-Hypophyseal System/metabolism , Fish Proteins/genetics , Fish Proteins/metabolism , Gonads/metabolism , Gonads/growth & development , Pituitary Gland/metabolism , Ovary/metabolism , Ovary/growth & development , Hypothalamic-Pituitary-Gonadal AxisABSTRACT
In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechaism of these processes in HUVECs are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls. As shown by RQ-MSP, the upstream DNA methylation level of the miR-520e promoter region was considerably increased in ACS patients. miR-520e was markedly down-regulated in ACS patients compared with healthy controls. In the ox-LDL-induced HUVECs injury model, DNA methylation of the upstream region of miR-520e was significantly increased. With increasing concentrations of the methylase inhibitor 5-Aza, miR-520e expression was upregulated. The silence of methyltransferase DNMT1, rather than DNMT3a or DNMT3b, abolished the influence of miR-520e expression by ox-LDL treatment in HUVECs. A dual luciferase reporter assay revealed that miR-520e regulated the TGFBR2 3'-UTR region. After silencing TGFBR2, the promoting effect of miR-520e inhibitor on cell proliferation and migration may be attenuated. In conclusion, the expression of miR-520e is modified by its promoter region DNA methylation, and miR520e and its promoter region DNA methylation may be potential biomarkers in atherosclerosis.
ABSTRACT
Multi-photon reduction (MPR) based on femtosecond laser makes rapid prototyping and molding in micro-nano scale feasible, but is limited in material selectivity due to lack of the understanding of the reaction mechanism in MPR process. In this paper, additively manufacturing of complex silver-based patterns through MPR is demonstrated. The effects of laser parameters, including laser pulse energies and scanning speeds, on the structural and chemical characteristics of the printed structures are systematically investigated. The results show that the geometric size of printed cubes deviates from the designed size further by increasing laser pulse energy or decreasing scanning speed. The reaction mechanism of MPR is revealed by studying the elemental composition and chemical structures of printed cubes. The evolution of Raman spectra upon the laser processing parameters suggests that the MPR process mainly includes two processes: reduction and decomposition. In the MPR process, silver ions are reduced and grow into particles by accepting the electrons from ethonal molecules; meanwhile carboxyl groups in polyvinylpyrrolidone are decomposed and form amorphous carbon that is attached on the surface of silver particles. The conductivity of silver wires fabricated by MPR reaches 2 × 105S m-1and stays relatively constant as varying their cross section area, suggesting excellent electrical conduction. The understanding of the MPR process would accelerate the development of MPR technology and the implementation of MPR in micro-electromechanical systems could therefore be envisioned.
ABSTRACT
The giant grouper fish (Epinephelus lanceolatus), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, we performed a transcriptome analysis to compare fresh and frozen sperm of the giant grouper with frozen storage times of 0, 23, 49, and 61 months. In total, 1911 differentially expressed genes (DEGs), including 91 in El-0-vs-El-23 (40 upregulated and 51 downregulated), 251 in El-0-vs-El-49 (152 upregulated and 69 downregulated), and 1569 in El-0-vs-El-61 (984 upregulated and 585 downregulated), were obtained in the giant grouper sperm. DEGs were significantly increased at 61 months of cryopreservation (p < 0.05). GO and KEGG enrichment analyses of the DEGs revealed significant enrichment in the pilus assembly, metabolic process, MAPK signaling pathway, apoptosis, and P53 signaling pathway. Time-series expression profiling of the DEGs showed that consistently upregulated modules were also significantly enriched in signaling pathways associated with apoptosis. Four genes, scarb1, odf3, exoc8, and atp5f1d, were associated with mitochondria and flagella in a weighted correlation network analysis. These genes may play an important role in the response to sperm freezing. The experimental results show that long-term cryopreservation results in freezing damage to the giant grouper sperm. This study provides rich data for studies of the mechanism underlying frozen fish sperm damage as well as a technical reference and evaluation index for the long-term cryopreservation of fish sperm.
Subject(s)
Cryopreservation , Spermatozoa , Transcriptome , Animals , Male , Cryopreservation/veterinary , Cryopreservation/methods , Spermatozoa/metabolism , Gene Expression Profiling/methods , Bass/genetics , Semen Preservation/veterinary , Semen Preservation/methods , Fish Proteins/genetics , Fish Proteins/metabolismABSTRACT
Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.
ABSTRACT
In X-ray computed tomography (CT) reconstructions of gas diffusion layers (GDLs), grayscale threshold selection is a critical issue. Although various selection methods exist, they all have their own drawbacks. This study investigates the influence of grayscale threshold on GDL properties and compares Otsu and porosity-adaptive thresholds. We utilized X-ray CT to reconstruct a Toray carbon paper sample (TGP-H-060) at a resolution of 2 µm. Using reconstructed 3D models generated under different grayscale thresholds, we performed structural analysis, computational fluid dynamics simulation, and compression simulation. We subsequently calculated porosity, tortuosity, permeability, and macroscopic stress-strain relationships, quantitatively analyzing the sensitivity of these parameters to the change of grayscale threshold. The results indicated that small change in the grayscale threshold can significantly impact the transport and mechanical properties of reconstructed GDLs. The difference between Otsu and porosity-adaptive thresholds is notable, and the porosity-adaptive threshold appears to be less accurate than the Otsu threshold.
ABSTRACT
Protein tyrosine phosphatases PTPN2 and PTPN1 (also known as PTP1B) have been implicated in a number of intracellular signaling pathways of immune cells. The inhibition of PTPN2 and PTPN1 has emerged as an attractive approach to sensitize T cell anti-tumor immunity. Two small molecule inhibitors have been entered the clinic. Here we report the design and development of compound 4, a novel small molecule PTPN2/N1 inhibitor demonstrating nanomolar inhibitory potency, good in vivo oral bioavailability, and robust in vivo antitumor efficacy.
Subject(s)
Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatase, Non-Receptor Type 2 , Protein Tyrosine Phosphatase, Non-Receptor Type 2/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Signal TransductionABSTRACT
The nitrogen deposition process, as an important phenomenon of global climate change and an important link in the nitrogen cycle, has had serious and far-reaching impacts on grassland ecosystems. This study aimed to investigate the survival adaptation strategies of plants of different functional groups under nitrogen deposition, and the study identified the following outcomes of differences in biomass changes by conducting in situ simulated nitrogen deposition experiments while integrating plant nutrient contents and soil physicochemical properties: (1) nitrogen addition enhanced the aboveground biomass of grassland communities, in which Poaceae were significantly affected by nitrogen addition. Additionally, nitrogen addition significantly influenced plant total nitrogen and total phosphorus; (2) nitrogen addition improved the plant growth environment, alleviated plant nitrogen limitation, and promoted plant phosphorus uptake; and (3) there was variability in the biomass responses of different functional groups to nitrogen addition. The level of nitrogen addition was the primary factor affecting differences in biomass changes, while nitrogen addition frequency was an important factor affecting changes in plant community structure.
ABSTRACT
The methionine adenosyltransferase MAT2A catalyzes the synthesis ofthe methyl donor S-adenosylmethionine (SAM) and thereby regulates critical aspects of metabolism and transcription. Aberrant MAT2A function can lead to metabolic and transcriptional reprogramming of cancer cells, and MAT2A has been shown to promote survival of MTAP-deficient tumors, a genetic alteration that occurs in â¼ 13 % of all tumors. Thus, MAT2A holds great promise as a novel anticancer target. Here, we report a novel series of MAT2A inhibitors generated by a fragment growing approach from AZ-28, a low-molecular weight MAT2A inhibitor with promising pre-clinical properties. X-ray co-crystal structure revealed that compound 7 fully occupies the allosteric pocket of MAT2A as a single molecule mimicking MAT2B. By introducing additional backbone interactions and rigidifying the requisite linker extensions, we generated compound 8, which exhibited single digit nanomolar enzymatic and sub-micromolar cellular inhibitory potency for MAT2A.
Subject(s)
Methionine Adenosyltransferase , Neoplasms , Humans , Allosteric Site , Methionine Adenosyltransferase/antagonists & inhibitors , Methionine Adenosyltransferase/metabolism , Mutation , S-Adenosylmethionine/metabolismABSTRACT
BACKGROUND: Over the past few decades, agonists binding to the benzodiazepine site of the GABAA receptor have been successfully developed as clinical drugs. Different modulators (agonist, antagonist, and reverse agonist) bound to benzodiazepine sites exhibit different or even opposite pharmacological effects, however, their structures are so similar that it is difficult to distinguish them based solely on molecular skeleton. This study aims to develop classification models for predicting the agonists. METHODS: 306 agonists or non-agonists were collected from literature. Six machine learning algorithms including RF, XGBoost, AdaBoost, GBoost, SVM, and ANN algorithms were employed for model development. Using six descriptors including 1D/2D Descriptors, ECFP4, 2D-Pharmacophore, MACCS, PubChem, and Estate fingerprint to characterize chemical structures. The model interpretability was explored by SHAP method. RESULTS: The best model demonstrated an AUC value of 0.905 and an MCC value of 0.808 for the test set. The PubMac-based model (PubMac-GB) achieved best AUC values of 0.935 for test set. The SHAP analysis results emphasized that MaccsFP62, ECFP_624, ECFP_724, and PubchemFP213 were the crucial molecular features. Applicability domain analysis was also performed to determine reliable prediction boundaries for the model. The PubMac-GB model was applied to virtual screening for potential GABAA agonists and the top 100 compounds were given. CONCLUSION: Overall, our ensemble learning-based model (PubMac-GB) achieved comparable performance and would be helpful in effectively identifying agonists of GABAA receptors.
Subject(s)
GABA-A Receptor Agonists , Receptors, GABA-A , Receptors, GABA-A/metabolism , Benzodiazepines , Machine Learning , gamma-Aminobutyric AcidABSTRACT
The extremely harsh environment of the high temperature plasma imposes strict requirements on the construction materials of the first wall in a fusion reactor. In this work, a refractory alloy system, WTaVTiZrx, with low activation and high entropy, was theoretically designed based on semi-empirical formula and produced using a laser cladding method. The effects of Zr proportions on the metallographic microstructure, phase composition, and alloy chemistry of a high-entropy alloy cladding layer were investigated using a metallographic microscope, XRD (X-ray diffraction), SEM (scanning electron microscope), and EDS (energy dispersive spectrometer), respectively. The high-entropy alloys have a single-phase BCC structure, and the cladding layers exhibit a typical dendritic microstructure feature. The evolution of microstructure and mechanical properties of the high-entropy alloys, with respect to annealing temperature, was studied to reveal the performance stability of the alloy at a high temperature. The microstructure of the annealed samples at 900 °C for 5-10 h did not show significant changes compared to the as-cast samples, and the microhardness increased to 988.52 HV, which was higher than that of the as-cast samples (725.08 HV). When annealed at 1100 °C for 5 h, the microstructure remained unchanged, and the microhardness increased. However, after annealing for 10 h, black substances appeared in the microstructure, and the microhardness decreased, but it was still higher than the matrix. When annealed at 1200 °C for 5-10 h, the microhardness did not increase significantly compared to the as-cast samples, and after annealing for 10 h, the microhardness was even lower than that of the as-cast samples. The phase of the high entropy alloy did not change significantly after high-temperature annealing, indicating good phase stability at high temperatures. After annealing for 10 h, the microhardness was lower than that of the as-cast samples. The phase of the high entropy alloy remained unchanged after high-temperature annealing, demonstrating good phase stability at high temperatures.
ABSTRACT
Stabilization of hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase domain enzymes (PHDs) represents a breakthrough in treating anemia associated with chronic kidney disease. Here, we identified a novel scaffold for noncarboxylic PHD inhibitors by utilizing structure-based drug design (SBDD) and generative models. Iterative optimization of potency and solubility resulted in compound 15 which potently inhibits PHD thus stabilizing HIF-α in vitro. X-ray cocrystal structure confirmed the binding model was distinct from previously reported carboxylic acid PHD inhibitors by pushing away the R383 and Y303 residues resulting in a larger inner subpocket. Furthermore, compound 15 demonstrated a favorable in vitro/in vivo absorption, distribution, metabolism, and excretion (ADME) profile, low drug-drug interaction risk, and clean early safety profiling. Functionally, oral administration of compound 15 at 10 mg/kg every day (QD) mitigated anemia in a 5/6 nephrectomy rat disease model.
Subject(s)
Anemia , Prolyl-Hydroxylase Inhibitors , Renal Insufficiency, Chronic , Rats , Animals , Prolyl Hydroxylases , Prolyl-Hydroxylase Inhibitors/pharmacology , Prolyl-Hydroxylase Inhibitors/therapeutic use , Anemia/drug therapy , Renal Insufficiency, Chronic/drug therapy , Administration, Oral , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Hypoxia-Inducible Factor 1, alpha SubunitABSTRACT
BACKGROUND AND AIMS: The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. MATERIALS AND METHODS: uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. RESULTS: Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729-0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage â ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727-0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. CONCLUSION: Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC.
Subject(s)
Carcinoma, Renal Cell , Extracellular Vesicles , Kidney Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Case-Control Studies , Biomarkers, Tumor/genetics , Biomarkers , Extracellular Vesicles/genetics , Kidney Neoplasms/diagnosis , Kidney Neoplasms/geneticsABSTRACT
BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the risk of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D), but the underlying mechanism has not been well elucidated. The circulating levels of proteins and metabolites reflect the overall state of the human body. This study aimed to evaluate the effect of dapagliflozin on the proteome and metabolome in patients with newly diagnosed T2D. METHODS: A total of 57 newly diagnosed T2D patients were enrolled, and received 12 weeks of dapagliflozin treatment (10 mg/d, AstraZeneca). Serum proteome and metabolome were investigated at the baseline and after dapagliflozin treatment. RESULTS: Dapagliflozin significantly decreased HbA1c, BMI, and HOMA-IR in T2D patients (all p < 0.01). Multivariate models indicated clear separations of proteomics and metabolomics data between the baseline and after dapagliflozin treatment. A total of 38 differentially abundant proteins including 23 increased and 15 decreased proteins, and 35 differentially abundant metabolites including 17 increased and 18 decreased metabolites, were identified. In addition to influencing glucose metabolism (glycolysis/gluconeogenesis and pentose phosphate pathway), dapagliflozin significantly increased sex hormone-binding globulin, transferrin receptor protein 1, disintegrin, and metalloprotease-like decysin-1 and apolipoprotein A-IV levels, and decreased complement C3, fibronectin, afamin, attractin, xanthine, and uric acid levels. CONCLUSIONS: The circulating proteome and metabolome in newly diagnosed T2D patients were significantly changed after dapagliflozin treatment. These changes in proteins and metabolites might be associated with the beneficial effect of dapagliflozin on cardiovascular and renal outcomes.
ABSTRACT
Background: Dendrobium, one of the largest genera in Orchidaceae, is popular not only for its aesthetic appeal but for its significant medicinal value. Growth-regulating factors (GRFs) play an essential role in plant growth and development. However, there is still a lack of information about the evolution and biological function analysis of the GRF gene family among Dendrobiumspecies. Methods: Growth-regulating factors from Dendrobium officinale Kimura et Migo and Dendrobium chrysotoxum Lindl. were identified by HMMER and BLAST. Detailed bioinformatics analysis was conducted to explore the evolution and function of GRF gene family in D. officinale and D. chrysotoxum using genomic data, transcriptome data and qRT-PCR technology. Results: Here, we evaluated the evolution of the GRF gene family based on the genome sequences of D. officinale and D. chrysotoxum. Inferred from phylogenetic trees, the GRF genes were classified into two clades, and each clade contains three subclades. Sequence comparison analysis revealed relatively conserved gene structures and motifs among members of the same subfamily, indicating a conserved evolution of GRF genes within Dendrobiumspecies. However, considering the distribution of orthologous DoGRFs and DcGRFs, and the differences in the number of GRFs among species, we suggest that the GRF gene family has undergone different evolutionary processes. A total of 361 cis-elements were detected, with 33, 141, and 187 related to plant growth and development, stress, and hormones, respectively. The tissue-specific expression of GRFs showed that DoGRF8 may have a significant function in the stem elongation of D. officinale. Moreover, four genes were up-regulated under Methyl-jasmonic acid/methyl jasmonate (MeJA) treatment, showing that DoGRFs and DcGRFs play a crucial role in stress response. These findings provide valuable information for further investigations into the evolution and function of GRF genes in D. officinale and D. chrysotoxum.
Subject(s)
Dendrobium , Dendrobium/genetics , Phylogeny , Transcriptome , Genes, PlantABSTRACT
BACKGROUND: Mitochondrial genomes are essential for deciphering the unique evolutionary history of seed plants. However, the rules of their extreme variation in genomic size, multi-chromosomal structure, and foreign sequences remain unresolved in most plant lineages, which further hindered the application of mitogenomes in phylogenetic analyses. RESULTS: Here, we took Dendrobium (Orchidaceae) which shows the great divergence of morphology and difficulty in species taxonomy as the study focus. We first de novo assembled two complete mitogenomes of Dendrobium wilsonii and Dendrobium henanense that were 763,005 bp and 807,551 bp long with multichromosomal structures. To understand the evolution of Dendrobium mitogenomes, we compared them with those of four other orchid species. The results showed great variations of repetitive and chloroplast-derived sequences in Dendrobium mitogenomes. Moreover, the intergenic content of Dendrobium mitogenomes has undergone expansion during evolution. We also newly sequenced mitogenomes of 26 Dendrobium species and reconstructed phylogenetic relationships of Dendrobium based on genomic mitochondrial and plastid data. The results indicated that the existence of chloroplast-derived sequences made the mitochondrial phylogeny display partial characteristics of the plastid phylogeny. Additionally, the mitochondrial phylogeny provided new insights into the phylogenetic relationships of Dendrobium species. CONCLUSIONS: Our study revealed the evolution of Dendrobium mitogenomes and the potential of mitogenomes in deciphering phylogenetic relationships at low taxonomic levels.
Subject(s)
Dendrobium , Genome, Mitochondrial , Orchidaceae , Phylogeny , Orchidaceae/genetics , Dendrobium/genetics , Genome, Mitochondrial/genetics , Genomics/methods , Base SequenceABSTRACT
Dendrobium orchids, which are among the most well-known species of orchids, are appreciated for their aesthetic appeal across the globe. Furthermore, due to their strict living conditions, they have accumulated high levels of active ingredients, resulting not only in their medicinal value but also in their strong ability to respond to harsh environments. The TCP gene family plays an important role in plant growth and development, and signal transduction. However, these genes have not been systematically investigated in Dendrobium species. In this study, we detected a total of 24, 23, and 14 candidate TCP members in the genome sequences of D. officinale, D. nobile, and D. chrysotoxum, respectively. These genes were classified into three clades on the basis of a phylogenetic analysis. The TCP gene numbers among Dendrobium species were still highly variable due to the independent loss of genes in the CIN clade. However, only three gene duplication events were detected, with only one tandem duplication event (DcTCP9/DcTCP10) in D. chrysotoxum and two pairs of paralogous DoTCP gene duplication events (DoTCP1/DoTCP23 and DoTCP16/DoTCP24) in D. officinale. A total of 25 cis-acting elements of TCPs related to hormone/stress and light responses were detected. Among them, the proportions of hormone response, light response, and stress response elements in D. officinale (100/421, 127/421, and 171/421) were similar to those in D. nobile (83/352, 87/352, and 161/352). Using qRT-PCR to determine their expression patterns under MeJA treatment, four DoTCPs (DoTCP2, DoTCP4, DoTCP6, and DoTCP14) were significantly upregulated under MeJA treatment, which indicates that TCP genes may play important roles in responding to stress. Under ABA treatment, seven DoTCPs (DoTCP3, DoTCP7, DoTCP9, DoTCP11, DoTCP14, DoTCP15, and DoTCP21) were significantly upregulated, indicating that TCP genes may also play an important role in hormone response. Therefore, these results can provide useful information for studying the evolution and function of TCP genes in Dendrobium species.
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The goal of local community detection algorithms is to explore the optimal community with a reference to a given node. Such algorithms typically include two primary processes: seed selection and community expansion. This study develops and tests a novel local community detection algorithm called OIRLCD that is based on the optimization of interaction relationships between nodes and the community. First, we introduce an improved seed selection method to solve the seed deviation problem. Second, this study uses a series of similarity indices to measure the interaction relationship between nodes and community. Third, this study uses a series of algorithms based on different similarity indices, and designs experiments to reveal the role of the similarity index in algorithms based on relationship optimization. The proposed algorithm was compared with five existing local community algorithms in both real-world networks and artificial networks. Experimental results show that the optimization of interaction relationship algorithms based on node similarity can detect communities accurately and efficiently. In addition, a good similarity index can highlight the advantages of the proposed algorithm based on interaction optimization.
ABSTRACT
OBJECTIVE: Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. METHODS: A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. RESULTS: The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). CONCLUSIONS: The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves' disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves' disease.In patients with Graves 'disease, serum DPP4 activity was positively correlated with TRAb levels.