ABSTRACT
Glycogen synthase kinase 3 (GSK3) family members serve as signaling hubs for plant development and stress responses, yet the underlying mechanism of their transcriptional regulation remains a long-standing mystery. Here we show that the transcription of SHAGGY-like kinase 11/12 (SK11/12), two members of the GSK3 gene family, is promoted by the splicing factor SmD1b, which is essential for distributing carbon sources into storage and protective components in Arabidopsis seeds. The chromatin recruitment of SmD1b at the SK11/12 loci promotes their transcription associated with co-transcriptional splicing of the first introns in the 5'-untranslated region of SK11/12. The loss of SmD1b function generates transcripts with unspliced introns that create disruptive R-loops to hamper the transcriptional elongation of SK11/12, in addition to compromising the recruitment of RNA polymerase II to the SK11/12 genomic regions. These effects imposed by SmD1b determine the transcription of SK11/12 to confer a key switch of carbon flow among metabolic pathways in zygotic and maternal tissues in seeds.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Carbon/metabolism , Glycogen Synthase Kinase 3/metabolism , Seeds/genetics , Seeds/metabolismABSTRACT
MicroRNA (miRNA) detection is a critical aspect of disease diagnosis, and recent studies indicate that miRNA-622 could be a potential target for lung cancer. Herein, Cu single atoms were anchored on graphitic carbon nitride (Cu SAs@CN) as a coreaction accelerator applied in luminol-H2O2 system, thereby establishing an efficient and sensitive electrochemiluminescence (ECL) biosensor for miRNA-622 detection. Cu SAs@CN was explored to possess excellent enzyme-like activities that promote the generation of abundant reactive oxygen species, which amplified ECL emission. Meanwhile, in order to improve the accuracy and sensitivity for miRNA-622 detection, the highly specific trans-cleavage ability of CRISPR/Cas12a was combined with a catalytic hairpin assembly strategy. Therefore, an ECL biosensor for miRNA-622 detection was systematically constructed as a proof of concept, achieving an ultralow limit of detection of 1.09 fM, and the feasibility was demonstrated in human serum samples. The findings of this research provide a promising strategy to enhance the ECL response using versatile single-atom catalysts, thus advancing the development of ECL biosensing applications.
Subject(s)
Biosensing Techniques , Copper , Electrochemical Techniques , Graphite , Luminescent Measurements , Luminol , MicroRNAs , Biosensing Techniques/methods , Humans , MicroRNAs/analysis , MicroRNAs/blood , Copper/chemistry , Graphite/chemistry , Luminol/chemistry , Limit of Detection , Hydrogen Peroxide/chemistry , Nitrogen Compounds/chemistry , Catalysis , CRISPR-Associated Proteins , CRISPR-Cas Systems , Bacterial Proteins , EndodeoxyribonucleasesABSTRACT
Nowadays, numerous studies have developed risk prediction models for sarcopenia in dialysis patients. However, the quality and performance of these models have not been integrated. The purpose of our study is to provide a comprehensive overview of the current risk prediction models for sarcopenia in dialysis patients and to offer a reference for the development of high-quality prediction models. Ten electronic databases were searched from inception to March 8, 2024. Two researchers independently assessed the risk of bias and applicability of the studies, and used Revman, 5.4, software to conduct a meta-analysis of common predictors in the models. A total of 12 studies described 13 risk prediction models for dialysis patients with sarcopenia. In dialysis patients, the prevalence of sarcopenia ranged from 6.60% to 63.73%. The area under curve (AUC) of the 13 models ranged from 0.776 to 0.945. Only six models (AUC ranging from 0.73 to 0.832) were internally validated, while two were externally evaluated (AUC ranging from 0.913 to 0.955). Most studies had a high risk of bias. The most common effective predictors in the models were age, body mass index, muscle circumference, and C-reactive protein. Our study suggests that developing a prediction model for the onset of sarcopenia in dialysis patients requires a rigorous design scheme, and future verification methods will necessitate multicenter external validation.
ABSTRACT
Osteoarthritis (OA), one of the major diseases afflicting the elderly, is a type of degenerative joint disease related to cartilage and synovium. This study aimed to clarify the role and mechanism of adipose mesenchymal stem cell (ADSC)-derived exosomes (Exos) in OA-induced chondrocyte degradation and synovial hyperplasia, thus improving the quality of life of patients. The rat OA model, chondrocytes, synovial fibroblast models and immunofluorescence were applied to observe the in vivo and in vitro functions of human ADSC (hADSC)-derived Exos in OA and its possible regulatory signaling pathways. Bioinformatics software and luciferase reporter assay were carried out to verify the mechanism of microRNA-376c-3p (miR-376c-3p) in hADSC-derived Exos in OA in vitro. Moreover, Safranine O-Fast Green Cartilage staining, Masson staining, immunohistochemistry and immunofluorescence were conducted to verify the role of miR-376c-3p in hADSC-derived Exos in OA in vivo. hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis both in vivo and in vitro models by repressing the WNT-beta-catenin signaling pathway. For the mechanism exploration in vitro, miR-376c-3p was raised in hADSC-derived Exos and mediated the fibrosis of synovial fibroblasts in OA, and miR-376c-3p targeted the 3'-untranslated region of WNT3 or WNT9a. Meanwhile, the in vivo experiments also corroborated that the miR-376c-3p in hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis. MiR-376c-3p in hADSC-derived Exos repressed the WNT-beta-catenin pathway by targeting WNT3 or WNT9a, and then mitigating OA-induced chondrocyte degradation and synovial fibrosis, thereby providing theoretical basis for clinical implementation of treatment.
Subject(s)
Exosomes , Mesenchymal Stem Cells , MicroRNAs , Osteoarthritis , Humans , Rats , Animals , Aged , MicroRNAs/genetics , MicroRNAs/metabolism , Exosomes/genetics , Exosomes/metabolism , beta Catenin/genetics , beta Catenin/metabolism , Quality of Life , Osteoarthritis/genetics , Osteoarthritis/therapy , Osteoarthritis/metabolism , Apoptosis , Chondrocytes , Wnt Signaling Pathway/genetics , Mesenchymal Stem Cells/metabolismABSTRACT
Cues of maternal and paternal origins interact to control seed development, and the underlying molecular mechanisms are still far from clear. Here, we show that TOPOISOMERASE Iα (TOP1α), UP-FRAMESHIFT SUPPRESSOR 1 (UPF1), and TRANSPARENT TESTA GLABRA2 (TTG2) gametophytically, biparentally regulate seed size in Arabidopsis. TOP1α and UPF1 are mainly expressed in antipodal cells, and loss of their function leads to ectopic TTG2 expression in these female gametophytic cells. We further demonstrate that TOP1α and UPF1 directly repress TTG2 expression through affecting its chromatin status and determine its relative expression in antipodal cells versus sperm cells, which controls seed size in a dosage-dependent and parent-of-origin-dependent manner. The molecular interplay among these three genes explains their biparental gametophytic effect during diploidy and interploidy reciprocal crosses. Taken together, our findings reveal a molecular framework of parental interaction for seed size control.
Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/growth & development , Arabidopsis/genetics , DNA Topoisomerases, Type I/genetics , RNA Helicases/genetics , Transcription Factors/genetics , Crosses, Genetic , Diploidy , Gene Dosage , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Genes, Plant , Models, Biological , Phenotype , Plants, Genetically Modified , Seeds/anatomy & histology , Seeds/genetics , Seeds/growth & development , TetraploidyABSTRACT
OBJECTIVES: To predict preoperative acute ischemic stroke (AIS) in acute type A aortic dissection (ATAAD). METHODS: In this multi-center retrospective study, 508 consecutive patients diagnosed as ATAAD between April 2020 and March 2021 were considered for inclusion. The patients were divided into a development cohort and two validation cohorts based on time periods and centers. Clinical data and imaging findings obtained were analyzed. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with preoperative AIS. The performance of resulting nomogram was evaluated in discrimination and calibration on all cohorts. RESULTS: A total of 224 patients were in the development cohort, 94 in the temporal validation cohort, and 118 in the geographical validation cohort. Six predictors were identified: age, syncope, D-dimer, moderate to severe aortic valve insufficiency, diameter ratio of true lumen in ascending aorta < 0.33, and common carotid artery dissection. The nomogram established showed good discrimination (area under the receiver operating characteristic curve [AUC], 0.803; 95% CI: 0.742, 0.864) and calibration (Hosmer-Lemeshow test p = 0.300) in the development cohort. External validation showed good discrimination and calibration abilities in both temporal (AUC, 0.778; 95% CI: 0.671, 0.885; Hosmer-Lemeshow test p = 0.161) and geographical cohort (AUC, 0.806; 95% CI: 0.717, 0.895; Hosmer-Lemeshow test p = 0.100). CONCLUSIONS: A nomogram, based on simple imaging and clinical variables collected on admission, showed good discrimination and calibration abilities in predicting preoperative AIS for ATAAD patients. KEY POINTS: ⢠A nomogram based on simple imaging and clinical findings may predict preoperative acute ischemic stroke in patients with acute type A aortic dissection in emergencies. ⢠The nomogram showed good discrimination and calibration abilities in validation cohorts.
Subject(s)
Aortic Dissection , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/complications , Stroke/diagnosis , Retrospective Studies , Nomograms , Aortic Dissection/diagnostic imagingABSTRACT
BACKGROUND: Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes. METHODS: Consecutive patients undergoing elective CTO-PCI were prospectively enrolled from Apr. 2018 to May 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. These data were analyzed accordingly for risk predictors of clinical outcome in patients who have diabetes and received successful CTO-PCI. RESULTS: A total of 1076 patients underwent CTO-PCI attempts. Diabetes was present in 374 (34.76%) patients, who had more hypertension, previous PCI and stroke. Regarding the coronary lesions, diabetic patients suffered more LCX lesion, multivessel disease, number of lesions per patient, blunt stump, calcification and higher J-CTO score (p < 0.05). In-hospital major adverse cardiac event (MACE) (4.13% vs. 5.35%; p = 0.362) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, the incidence of MACE and all-cause mortality were also similar in the two groups (p > 0.05). Number of lesions per patient was an independent risk factor of MACE and all-cause mortality (p < 0.001) 1 year after successful CTO-PCI. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, patients with diabetes showed similar degrees of improvement to those without diabetes (P > 0.05). CONCLUSIONS: Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptoms and QOL in CTO patients with diabetes.
Subject(s)
Coronary Occlusion , Diabetes Mellitus , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/surgery , Quality of Life , Coronary Angiography , Treatment Outcome , Risk Factors , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/etiology , Chronic Disease , RegistriesABSTRACT
BACKGROUND: The feasibility and long-term outcomes of the CrossBoss/Stingray for treating coronary chronic total occlusions (CTO) with distal diffuse disease landing zone remain unclear. METHODS: Consecutive CTO patients with distal diffuse lesions that underwent percutaneous coronary intervention by the CrossBoss/Stingray system at Xijing Hospital from April 2016 to October 2020, were included. Patients were analyzed by two groups according to the extent of stenosis in the distal landing zone: 50%-70% stenosis (moderate stenosis group) and >70% stenosis (severe stenosis group). The primary efficacy outcome was technical success, defined as the frequency of true lumen guidewire placement distal to the CTO. The composite endpoint of all-cause death, any stroke, or any revascularization was also explored. RESULTS: A total of 91 consecutive patients were included, with 32 patients in the moderate stenosis group and 59 patients in the severe stenosis group. The mean J-CTO score was 2.5 ± 1.1. The technical success rate was 79.1% (72/91) in the overall population and was similar between the 2 groups: 78.1% (25/32) and 79.7% (47/59) (p = 0.608). No coronary perforation occurred. With a median follow-up of 29 months (IQR: 53-92), the estimated rate of the composite endpoint of all-cause death, any stroke, or any revascularization was 50.4% (all-cause death: 16.6%, any stroke: 1.1%, any revascularization: 36.5%) in the overall population. No significant difference was observed in the rate of the composite endpoint between the moderate stenosis group and the severe stenosis group (45.1% vs. 54.3%, respectively, p = 0.797). CONCLUSIONS: In CTO lesions with distal diffuse disease landing zone, the technical success rates of CrossBoss/Stingray and the long-term clinical outcomes were not significantly different between the moderate stenosis group (50%-70%) and the severe stenosis group (>70%). However, the relatively high rate of long-term clinical outcomes, especially any revascularization, warrants further investigations on this indication in future studies.
Subject(s)
Coronary Occlusion , Percutaneous Coronary Intervention , Skates, Fish , Stroke , Animals , Chronic Disease , Constriction, Pathologic/etiology , Coronary Angiography , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/therapy , Feasibility Studies , Humans , Percutaneous Coronary Intervention/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: At present, there is a lack of direct evidence to confirm whether the recommendations of the World Health Organization can play a role in fitness and disease prevention in the Chinese population. Therefore, we aimed to analyse 7-year longitudinal survey data to explore whether the physical activity volume recommended by the World Health Organization can help Chinese middle-aged and elderly people reduce the risk of heart disease. METHODS: Data for the 8327 participants who were finally included in this study were derived from the 7-year data of the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. The physical activity volume is expressed by the product of physical frequency and duration, and heart disease is screened according to self-reported diagnosis and related treatment. The relationship between different physical activity volume groups and the incidence rate of heart disease was determined by a multivariate Cox proportional hazards regression model. RESULTS: After adjusting for all covariates, participants meeting the WHO's recommendations had a 20% lower risk of heart disease than those who did not meet the WHO's recommendations (HR = 0.80, 95% = 0.68-0.96). Subgroup analysis showed that among the participants meeting the WHO's recommendations, men (HR = 0.71) had a lower risk of heart disease than women (HR = 0.74); in addition, the risk of heart disease was significantly reduced in participants who were middle-aged (26%), had a normal BMI range (49%), did not have hypertension (24%), did not have hyperlipidaemia (21%) and did not have lung disease (21%). It should be noted that the risk of heart disease was reduced by 72 and 67% in participants with untreated hyperlipidaemia and untreated lung disease, respectively. CONCLUSIONS: This study revealed that meeting the WHO's recommendations for physical activity volume can reduce the risk of heart disease in middle-aged and older people in China and can also effectively prevent heart disease for people with some common chronic diseases, such as hyperlipidaemia and lung disease. The results showed that physical activity for leisure and exercise had a lower preventive effect on heart disease than physical activity for a job, which may be related to the inappropriate leisure and exercise methods of the participants. TRIAL REGISTRATION: IRB00001052-11015.
Subject(s)
Heart Diseases , Lung Diseases , Aged , China/epidemiology , Exercise , Female , Heart Diseases/diagnosis , Heart Diseases/epidemiology , Heart Diseases/prevention & control , Humans , Longitudinal Studies , Male , Middle Aged , World Health OrganizationABSTRACT
Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here, we identified a BR-insensitive rice mutant, reduced leaf angle1 (rla1), and cloned the corresponding gene. RLA1 was identical to the previously reported SMALL ORGAN SIZE1 (SMOS1), which was cloned from another allele. RLA1/SMOS1 encodes a transcription factor with an APETALA2 DNA binding domain. Genetic analysis indicated that RLA1/SMOS1 functions as a positive regulator in the BR signaling pathway and is required for the function of BRASSINAZOLE-RESISTANT1 (OsBZR1). In addition, RLA1/SMOS1 can interact with OsBZR1 to enhance its transcriptional activity. GSK2 can interact with and phosphorylate RLA1/SMOS1 to reduce its stability. These results demonstrate that RLA1/SMOS1 acts as an integrator of the transcriptional complex directly downstream of GSK2 and plays an essential role in BR signaling and plant development in rice.
Subject(s)
Brassinosteroids/metabolism , Oryza/metabolism , Plant Proteins/physiology , Transcription Factors/physiology , Binding Sites , Cloning, Molecular , Gene Expression Regulation, Plant , Genetic Complementation Test , Oryza/genetics , Oryza/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Picosecond pulse electrical fields (psPEFs), due to their high temporal-resolution accuracy and localization, were viewed as a potential targeted and noninvasive method for neuromodulation. However, few studies have reported psPEFs regulating neuronal activity in vivo. In this paper, a preliminary study on psPEFs regulating action potentials in hippocampus CA1 of rats in vivo was carried out. By analyzing the neuronal spike firing rate in hippocampus CA1 pre- and post-psPEF stimulation, effects of frequency, duration, and dosimetry of psPEFs were studied. The psPEF used in this study had a pulse width of 500 ps and a field strength of 1 kV/mm, established by 1 kV picosecond voltage pulses. Results showed that the psPEF suppressed spike firing in hippocampal CA1 neurons. The suppression effect was found to be significant except for 10 s, 10 Hz. For short-duration stimulation (10 s), the inhibition rate of spike firing increased with frequency. At longer stimulation durations (1 and 2 min), the inhibition rate increased and decreased alternately as the frequency increased. Despite this, the inhibition rate at high frequencies (5 and 10 kHz) was significantly larger than that at 10 and 100 Hz. A cumulative effect of psPEF on spike firing inhibition was found at low frequencies (10 and 100 Hz), which was saturated when frequency reached 500 Hz or higher. This paper conducts a study on psPEF regulating spike firing in hippocampal CA1 in vivo for the first time and guides subsequent study on psPEF achieving noninvasive neuromodulation. © 2020 Bioelectromagnetics Society.
Subject(s)
CA1 Region, Hippocampal/physiology , Electricity , Animals , CA1 Region, Hippocampal/cytology , Male , Neurons/cytology , RatsABSTRACT
OBJECTIVE: Adiponectin (APN) circulates as high-molecular weight (HMW), medium-molecular weight (MMW), and low-molecular weight (LMW) forms. Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Currently, the role of LMW, MMW, and HMW APN remains largely unclear in NAFLD. METHODS: We examined the variation of these forms and analyzed the related clinical characteristics in NAFLD. A total of 63 male NAFLD patients (mean age: 43.00 ± 6.10 years) and 70 healthy male subjects (mean age: 42.53 ± 7.98 years) were included in the study. Total APN and other clinical characteristics were measured. The changes in HMW, MMW, and LMW APN were determined in NAFLD patients and NAFLD patients on a high-fat diet, and the association between the groups was further analyzed. RESULTS: Decreased levels of total APN and three APN isoforms were found in NAFLD. Significantly decreased levels of HMW (P < .01) and MMW (P < .001) were observed in NAFLD of high-fat diet patients. In NAFLD patients, height (R = -.270, P = .032) and N-epsilon-(carboxymethyl) lysine (R = -.259, P = .040) significantly correlated with total APN. HMW APN was significantly associated with fasting plasma glucose (R = .350, P = .016), alanine aminotransferase (R = -.321, P = .029), and aspartate aminotransferase (R = -.295, P = .045). Additionally, MMW APN was significantly associated with total cholesterol (R = .357, P = .014) and high-density lipoprotein (R = .556, P < .0001). Low-density lipoprotein (R = -.283, P = .054) was also clearly associated with LMW APN in NAFLD patients. CONCLUSION: These results suggest that HMW and MMW APN may be involved in the pathogenesis and progression of NAFLD.
Subject(s)
Adiponectin/blood , Non-alcoholic Fatty Liver Disease/blood , Adiponectin/metabolism , Adult , Humans , Male , Molecular Weight , Protein Isoforms/blood , Protein Isoforms/metabolismABSTRACT
BACKGROUND: Steep pulse therapy can irreversible electrically brackdown of tumor membrance and cause cell death. In previous studies, we investigated the effect of steep pulsed electroporation on the killing of large cell lung cancer cell line L981- in vitro, and determined the best parameters for killing lung cancer cells by steep pulse technology. But the optimal parameters and the mechanisms of steep pulse irreversible electroporation technology on nude mouse tumor model are unclear. METHODS: Three settings of steep pulse therapy parameters were applied to the nude mouse model. An in vivo imaging system was employed to observe the effect of different parameters on the mouse model. The pathological changes of the tumor tissue and immunofluorescence data on Caspase-3 protein expression were recorded. RESULTS: Under the in vivo imaging system, the steep pulse had an obvious inhibitory effect on the transplanted tumor in the nude mouse model. Pathological tests showed that occurrence of necrosis and apoptosis and expression of Caspase-3 protein in the tumor tissue were increased compared to those in the normal tissue. CONCLUSIONS: Steep pulse irreversible electroporation technology showed a promising antitumor effect in the nude mouse tumor model. With splint-type electrode, the best treatment parameters determined for the nude mouse tumor model were voltage amplitude 2000 V/cm, pulse width 100 µs, pulse frequency 1 Hz, pulse number 60, and repeat time 3. Moreover, steep pulse induced coagulative necrosis of tumor tissue by cell apoptosis.
Subject(s)
Carcinoma, Large Cell/pathology , Electric Stimulation Therapy , Electroporation/methods , Lung Neoplasms/pathology , Necrosis , Animals , Apoptosis , Carcinoma, Large Cell/therapy , Cell Proliferation , Female , Humans , Lung Neoplasms/therapy , Mice , Mice, Inbred BALB C , Mice, Nude , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Most porous media (just like catalyst pellets) have complicated pore structures, and understanding the coupling of the diffusion and reaction processes in these pores is very important for improving their performance. In this work, a diffusion factor (D) and a reaction factor (R) are proposed to quantitatively describe the diffusion and reaction performance in these pores respectively at molecular level. The yield in unit time is used to quantify their productivity and is expressed as the product of D and R. Molecular dynamic simulations with the hard-sphere algorithm are carried out to study the reaction-diffusion coupling in several simple pore structures with the same volume, such as straight, T-shaped, and cross-shaped pores. The reaction formula based on activation energy is given for a simple irreversible reaction process from A to B. In terms of the proposed factors, D and R, analysis on the simulation results shows clearly that the overall productivity of these pore structures depends on the competition of D and R, which are both determined by the size and shape of the pore structures. The results demonstrate the effectiveness of the simulation approach used for evaluating the performance of the simple pore structures for simple reactions and the potential of its application in more complicated and practical cases. It also suggests the effectiveness of the proposed factors, D and R, for charactering the diffusion and reaction processes at molecular level.
ABSTRACT
Seed storage reserves mainly consist of starch, triacylglycerols, and storage proteins. They not only provide energy for seed germination and seedling establishment, but also supply essential dietary nutrients for human beings and animals. So far, the regulatory networks that govern the accumulation of seed storage reserves in plants are still largely unknown. Here, we show that TRANSPARENT TESTA GLABRA1 (TTG1), which encodes a WD40 repeat transcription factor involved in many aspects of plant development, plays an important role in mediating the accumulation of seed storage reserves in Arabidopsis (Arabidopsis thaliana). The dry weight of ttg1-1 embryos significantly increases compared with that of wild-type embryos, which is accompanied by an increase in the contents of starch, total protein, and fatty acids in ttg1-1 seeds. FUSCA3 (FUS3), a master regulator of seed maturation, binds directly to the TTG1 genomic region and suppresses TTG1 expression in developing seeds. TTG1 negatively regulates the accumulation of seed storage proteins partially through transcriptional repression of 2S3, a gene encoding a 2S albumin precursor. TTG1 also indirectly suppresses the expression of genes involved in either seed development or synthesis/modification of fatty acids in developing seeds. In addition, we demonstrate that the maternal allele of the TTG1 gene suppresses the accumulation of storage proteins and fatty acids in seeds. Our results suggest that TTG1 is a direct target of FUS3 in the framework of the regulatory hierarchy controlling seed filling and regulates the accumulation of seed storage proteins and fatty acids during the seed maturation process.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Seeds/metabolism , Alleles , Arabidopsis/embryology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Fatty Acids/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Models, Biological , Mutation/genetics , Real-Time Polymerase Chain Reaction , Seeds/genetics , Transcription Factors/metabolismABSTRACT
The phytohormone ABA is a key stress signal in plants. Although the identification of ABA receptors led to significant progress in understanding the Arabidopsis ABA signaling pathway, there are still many unsolved mysteries regarding ABA signaling in monocots, such as rice. Here, we report that a rice ortholog of AtABI1 and AtABI2, named OsABI-LIKE2 (OsABIL2), plays a negative role in rice ABA signaling. Overexpression of OsABIL2 not only led to ABA insensitivity, but also significantly altered plant developmental phenotypes, including stomatal density and root architecture, which probably caused the hypersensitivity to drought stress. OsABIL2 interacts with OsPYL1, SAPK8 and SAPK10 both in vitro and in vivo, and the phosphatase activity of OsABIL2 was repressed by ABA-bound OsPYL1. However, unlike many other solely nuclear-localized clade A type 2C protein phosphatases (PP2Cs), OsABIL2 is localized in both the nucleus and cytosol. Furthermore, OsABIL2 interacts with and co-localized with OsPYL1 mainly in the cytosol, and ABA treatment regulates the nucleus-cytosol distribution of OsABIL2, suggesting a different mechanism for the activation of ABA signaling. Taken together, this study provides significant insights into rice ABA signaling and indicates the important role of OsABIL2 in regulating root development.
Subject(s)
Abscisic Acid/pharmacology , Droughts , Oryza/metabolism , Plant Proteins/metabolism , Plant Roots/anatomy & histology , Signal Transduction/drug effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Feedback, Physiological , Oryza/drug effects , Phosphorylation/drug effects , Plant Leaves/drug effects , Plant Leaves/metabolism , Plant Leaves/ultrastructure , Plant Roots/drug effects , Plant Roots/metabolism , Plant Transpiration/drug effects , Protein Binding/drug effects , Protein Transport/drug effects , Subcellular Fractions/metabolism , Transcription, Genetic/drug effectsABSTRACT
OBJECTIVES: To examine the safety and efficacy of immediate rotational atherectomy (RA) in nondilatable calcified coronary lesions complicated by coronary dissection during percutaneous coronary intervention (PCI). BACKGROUND: In the presence of coronary dissection in nondilatable calcified coronary lesions, conservative management is suggested to permit the dissection to heal prior to treatment with RA. However, many patients have frequent angina attacks and some patients develop serious complications during this period. METHODS: One hundred and nighty-eight patients with severe coronary calcification underwent PCI, and were randomized into immediate (n = 105) or delayed RA group (n = 93) when coronary dissections occur. The primary endpoint of the present study was all-cause death including cardiac and non-cardiac death in 4 years follow-up. Non-fatal myocardial infarction, stent thrombosis, cardiac tamponade, stroke, target lesion revascularization, New York Heart Association (NYHA) class IV heart failure were analyzed as secondary end points. RESULTS: At a follow-up of 4 years, event-free survival rates were not statistically different between the immediate and delayed RA group (81.9% vs 80.6%, P = 0.820). Rates of PCI- and RA-related major adverse cardiac events (MACE) and severe RA-related complications were not statistically different between groups. Luminal loss was not significantly different between the immediate and delayed RA group as evaluated by Intravascular ultrasound (IVUS). Two cases in the delayed RA group experienced myocardial infarction during the 4-week waiting. CONCLUSION: This study indicates that immediate RA during PCI is safe and effective in patients with coronary artery dissection.
Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Intraoperative Complications , Percutaneous Coronary Intervention/adverse effects , Vascular Calcification , Aged , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/methods , China , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Early Medical Intervention , Female , Humans , Intraoperative Complications/diagnosis , Intraoperative Complications/surgery , Male , Middle Aged , Outcome Assessment, Health Care , Survival Analysis , Time Factors , Treatment Outcome , Vascular Calcification/diagnosis , Vascular Calcification/mortality , Vascular Calcification/surgeryABSTRACT
Aiming to provide a feasible crawling motion analysis method for clinical application, this study introduced electromyography (EMG)-based motion intention recognition technology into the pattern recognition of inter-limb coordination during human crawling for the first time. Eight inter-limb coordination modes (ILCMs) were defined. Ten adult participants were recruited, and each participant performed hands-knees crawling at low, medium, and fast speeds in self-selected ILCMs and the eight predefined ILCMs, respectively. EMG signals for pattern recognition were collected from 30 limbs and trunk muscles, and pressure signals for crawling cycle segmentation were collected from the left palm. The pattern recognition experiments were conducted in participant-specific, multi-participant, and participant-independent ways, respectively, adopting three different classifiers, including bidirectional long short-term memory (BiLSTM) network, support vector machine (SVM), and k-nearest neighbor (KNN). The experimental results show that EMG-based pattern recognition schemes could classify the eight ILCMs with high recognition rates, thereby confirming the feasibility of providing an EMG-based crawling motion analysis method for clinical doctors. Furthermore, based on the classification results of self-selected ILCMs at different speeds and the statistical results of stance duration, swing duration, and the duty factors of stance phase, the possible reasons why humans chose various ILCMs at different crawling speeds were discussed. The research results have potential application value for evaluating crawling function, understanding abnormal crawling control mechanisms, and designing rehabilitation robots.
ABSTRACT
Background: Congenital pseudarthrosis of the tibia is a limb deformity, which can be distressing for the affected patients and the pediatric orthopedic surgeons involved. We hypothesized that the modified McFarland procedure would avoid fractures and even have a corrective effect on the affected tibia in congenital pseudarthrosis of the tibia patients. Toward this end, we evaluated the midterm results of treating congenital pseudarthrosis of the tibia patients of Crawford Type I and II with allograft bypass combined with long-term bracing. Methods: This study retrospectively evaluated 7 patients with congenital pseudarthrosis of the tibia who were treated with allograft bypass combined with long-term bracing between 2009 and 2018. The median follow-up was 7.0 years (range 3.8-10.0 years). The medical records and radiographs were reviewed for demographic data, clinical characteristics, outcomes, and complications. Results: At the time of the last follow-up, all allografts revealed complete consolidation in the patients' tibiae at both ends. All patients presented no functional restriction of the lower limbs and no amputation or non-union has occurred. Most of the obvious deformities of the tibia diaphysis or ankle joint were corrected. Two complications occurred that required successful revision surgery. Conclusion: In this series of seven congenital pseudarthrosis of the tibia patients, the allograft bypass technique showed satisfactory midterm results and validated our hypothesis. For congenital pseudarthrosis of the tibia patients of Crawford Type I and II, this procedure combined with long-term bracing, which involves the affected leg only, can delay or possibly prevent fractures, decrease tibial malalignment, and preserve leg length. Level of evidence: level IV.
ABSTRACT
Synovial sarcoma is a rare and highly malignant soft tissue sarcoma. The inconspicuous and diversity of its early symptoms make it a highly misdiagnosed disease. The management of synovial sarcomas is challenging as they are rare and have a poor prognosis. Early and correct diagnosis and treatment are critical for clinical outcomes. Misdiagnosis or delayed diagnosis can have devastating consequences for the patient. The detection of SS18 gene rearrangement is considered a powerful tool in establishing the diagnosis of synovial sarcomas. Biopsies and testing for gene rearrangements are recommended for all patients in whom SS cannot be excluded. Surgery is the mainstay of treatment for synovial sarcomas. Neoadjuvant/adjuvant radiotherapy is recommended for patients with big tumors (>5 cm) or positive resection margins, and neoadjuvant/adjuvant chemotherapy is recommended for patients with high-risk tumors or advanced diseases. This article reviews synovial sarcomas from the perspectives of clinical and radiological presentation, histological and cytogenetic analysis, differential diagnosis, treatment, and prognosis.