RESUMO
Brassinosteroid (BR) phytohormones play crucial roles in regulating internode elongation in rice (Oryza sativa). However, the underlying mechanism remains largely unclear. The dwarf and low-tillering (dlt) mutant is a mild BR-signaling-defective mutant. Here, we identify two dlt enhancers that show more severe shortening of the lower internodes compared to the uppermost internode (IN1). Both mutants carry alleles of ORYZA SATIVA HOMEOBOX 15 (OSH15), the founding gene for dwarf6-type mutants, which have shortened lower internodes but not IN1. Consistent with the mutant phenotype, OSH15 expression is much stronger in lower internodes, particularly in IN2, than IN1. The osh15 single mutants have impaired BR sensitivity accompanied by enhanced BR synthesis in seedlings. DLT physically interacts with OSH15 to co-regulate many genes in seedlings and internodes. OSH15 targets and promotes the expression of the BR receptor gene BR INSENSITIVE1 (OsBRI1), and DLT facilitates this regulation in a dosage-dependent manner. In osh15, dlt, and osh15 dlt, BR levels are higher in seedlings and panicles, but unexpectedly lower in internodes compared with the wild-type. Taken together, our results suggest that DLT interacts with OSH15, which functions in the lower internodes, to modulate rice internode elongation via orchestrating BR signaling and metabolism.
Assuntos
Oryza , Brassinosteroides/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genes Homeobox , Proteínas de Homeodomínio/genética , Mutação/genética , Oryza/genética , Oryza/metabolismo , Fenótipo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Heart failure (HF) remains prevalent in patients who survived myocardial infarction (MI). Despite the accessibility of the primary percutaneous coronary intervention and medications that alleviate ventricular remodeling with functional improvement, there is an urgent need for clinicians and basic scientists to further reveal the mechanisms behind post-MI HF as well as investigate earlier and more efficient treatment after MI. Growing numbers of studies have highlighted the crucial role of macrophages in cardiac repair and remodeling following MI, and timely intervention targeting the immune response via macrophages may represent a promising therapeutic avenue. Recently, technology such as single-cell sequencing has provided us with an updated and in-depth understanding of the role of macrophages in MI. Meanwhile, the development of biomaterials has made it possible for macrophage-targeted therapy. Thus, an overall and thorough understanding of the role of macrophages in post-MI HF and the current development status of macrophage-based therapy will assist in the further study and development of macrophage-targeted treatment for post-infarction cardiac remodeling. This review synthesizes the spatiotemporal dynamics, function, mechanism and signaling of macrophages in the process of HF after MI, as well as discusses the emerging bio-materials and possible therapeutic agents targeting macrophages for post-MI HF.
RESUMO
BACKGROUND: During arthroscopic rotator cuff repair (ARCR), clear surgical field visibility (SFV) is the basis of successful surgery, but the choice of anesthesia maintenance drugs may have different effects on SFV. In this study, we aimed to compare the effects of propofol- and sevoflurane-based general anesthesia on SFV in patients undergoing ARCR. METHODS: Patients (n = 130) undergoing elective ARCR in the lateral decubitus position were randomized into either the propofol group or sevoflurane group (65 per group). The duration of surgery and increased pressure irrigation (IPI), Boezaart score, rocuronium consumption and usage of remifentanil were recorded. The time of both spontaneous respiration recovery and extubation and the incidences of postoperative nausea and vomiting and agitation were also recorded. RESULTS: The Boezaart score, duration of IPI and ratio of the duration of IPI to the duration of surgery (IPI/S ratio) were similar between the groups (P > 0.05). Rocuronium consumption, number of patients requiring remifentanil infusion and total remifentanil consumption were significantly lower in the sevoflurane group (P < 0.05). The spontaneous respiration recovery time was significantly longer in the propofol group (P < 0.05), but there were no differences in the extubation time between the groups(P > 0.05). CONCLUSIONS: Compared with propofol, sevoflurane provides equally clear SFV while improving the convenience of anesthesia maintenance in ARCR patients with interscalene plexus (ISB) combined with general anesthesia. TRIAL REGISTRATION: This single-center, prospective, RCT was retrospective registered at Chinese Clinical Trial Registry with the registration number ChiCTR2300072110 (02/06/2023).
Assuntos
Anestésicos Inalatórios , Éteres Metílicos , Propofol , Humanos , Propofol/farmacologia , Sevoflurano , Remifentanil , Rocurônio , Estudos Prospectivos , Manguito Rotador/cirurgia , Estudos Retrospectivos , Éteres Metílicos/farmacologia , Piperidinas/farmacologia , Anestesia Geral , Anestésicos Intravenosos/farmacologia , Anestésicos Inalatórios/farmacologiaRESUMO
BACKGROUND: The objective of this research is to clarify the impact of periodontitis on overall and cardiovascular-related death rates among hypertensive individuals. METHOD: A total of 5665 individuals with hypertension were included from the National Health and Nutrition Examination Survey (NHANES) data spanning 2001-2004 and 2009-2014. These individuals were divided into two groups based on the presence or absence of periodontitis and further stratified by the severity of periodontitis. We employed weighted multivariate Cox proportional hazards regression and Kaplan-Meier curves (log-rank test) to evaluate the impact of periodontitis on all-cause and cardiovascular mortality. Additional analyses, including adjustments for various covariates, subgroups, and sensitivity analyses, were conducted to ensure the robustness and reliability of our results. RESULT: Over an average follow-up duration of 10.22 years, there were 1,122 all-cause and 297 cardiovascular deaths. Individuals with periodontitis exhibited an elevated risk of all-cause mortality (HR = 1.33, 95% CI 1.18-1.51; p < 0.0001) and cardiovascular mortality (HR = 1.48, 95% CI 1.15-1.89; p = 0.002). Moreover, we observed a progressive increase in both all-cause mortality and cardiovascular mortality (p for trend are both lower than 0.001) and correlating with the severity of periodontitis. These associations remained consistent across various subgroup and sensitivity analyses. CONCLUSION: Our findings suggest a significant association between periodontitis and increased risks of all-cause and cardiovascular mortality among hypertensive individuals. Notably, the severity of periodontitis appears to be a critical factor, with moderate to severe cases exerting a more pronounced impact on all-cause mortality. Additionally, cardiovascular disease mortality significantlly increases in individuals with varying degrees of periodontitis.
Assuntos
Doenças Cardiovasculares , Causas de Morte , Hipertensão , Inquéritos Nutricionais , Periodontite , Humanos , Periodontite/complicações , Periodontite/mortalidade , Hipertensão/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/complicações , Adulto , Estudos de Coortes , Estados Unidos/epidemiologia , Idoso , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
Maintaining stable, high yields under fluctuating environmental conditions is a long-standing goal of crop improvement but is challenging due to internal trade-off mechanisms, which are poorly understood. Here, we identify ARGONAUTE2 (AGO2) as a candidate target for achieving this goal in rice (Oryza sativa). Overexpressing AGO2 led to a simultaneous increase in salt tolerance and grain length. These benefits were achieved via the activation of BIG GRAIN3 (BG3), encoding a purine permease potentially involved in cytokinin transport. AGO2 can become enriched on the BG3 locus and alter its histone methylation level, thus promoting BG3 expression. Cytokinin levels decreased in shoots but increased in roots of AGO2-overexpressing plants. While bg3 knockout mutants were hypersensitive to salt stress, plants overexpressing BG3 showed strong salt tolerance and large grains. The knockout of BG3 significantly reduced grain length and salt tolerance in AGO2-overexpressing plants. Both genes were transcriptionally suppressed by salt treatment. Salt treatment markedly increased cytokinin levels in roots but decreased them in shoots, resulting in a hormone distribution pattern similar to that in AGO2-overexpressing plants. These findings highlight the critical roles of the spatial distribution of cytokinins in both stress responses and grain development. Therefore, optimizing cytokinin distribution represents a promising strategy for improving both grain yield and stress tolerance in rice.
Assuntos
Citocininas/metabolismo , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Tolerância ao Sal/fisiologia , Sementes/fisiologia , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Mutação , Oryza/efeitos dos fármacos , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente ModificadasRESUMO
Recently, the supra-normal left ventricular ejection fraction (snLVEF) has been proposed, based on extensive datasets indicating increased all-cause mortality in individuals with an LVEF exceeding 65%. However, the implications of an LVEF > 65% in the context of acute coronary syndrome (ACS) remain underexplored.The aim of the present study was to investigate the correlation between supra-normal left ventricular ejection fraction (snLVEF) and major adverse cardiovascular events (MACE) in patients with ACS.Methods: A total of 874 ACS patients (560 men, mean age 59.5 ± 10.0; 314 women, mean age 61.5 ± 8.9) who underwent their first coronary angiography during the period from March 2013 to October 2015 were divided into 2 groups: normal LVEF (nLVEF) (55% ≤ EF ≤ 65%) and snLVEF (EF > 65%), according to their echocardiography results. The patients were evaluated for MACE after surgery by collecting clinical data and long-term follow-up data. This correlation was further analyzed by Kaplan-Meier analysis and Cox regression analysis.The follow-up data revealed a significantly higher incidence of MACE among snLVEF patients compared to the nLVEF group (15.6% versus 7.4%; P = 0.020). This heightened risk persisted even after adjustment for multiple variables, indicating a strong association between snLVEF and increased MACE risk (HR: 2.346; 95% CI: 1.196-4.602; P = 0.013).SnLVEF was independently associated with poor prognosis after ACS. Enhanced management strategies for snLVEF patients could potentially reduce the incidence of MACE in ACS patients.
Assuntos
Síndrome Coronariana Aguda , Função Ventricular Esquerda , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Volume Sistólico , Prognóstico , Análise de RegressãoRESUMO
Brassinosteroids (BRs) regulate various agronomic traits such as plant height, leaf angle, and grain size in rice (Oryza sativa L.); thus, BR signaling components are promising targets for molecular rational design. However, genetic materials for BR-signaling genes or family members remain limited in rice. Here, by genome editing using clustered regularly interspaced short palindromic repeats (CRSPR)/Cas9 tools, we generated a panel of single, double, triple, or quadruple mutants within three BR signaling gene families, including GSK3/SHAGGY-LIKE KINASE1 (GSK1)-GSK4, BRASSINAZOLE-RESISTANT1 (OsBZR1)-OsBZR4, and protein phosphatases with kelch-like (PPKL)1-PPKL3, under the same background (Zhonghua11, japonica). The high-order mutants were produced by either simultaneously targeting multiple sites on different genes of one family (GSKs and PPKLs) or targeting the overlapping sequences of family members (OsBZRs). The mutants exhibited a diversity of plant height, leaf angle, and grain morphology. Comparison analysis of the phenotypes together with BR sensitivity tests suggested the existence of functional redundancy, differentiation, or dominancy among the members within each family. In addition, we generated a set of transgenic plants overexpressing GSK2, OsBZR1/2, and PPKL2, respectively, in wild-type or activated forms with fusion of different tags, and also verified the protein response to BR application. Collectively, these plants greatly enriched the diversity of important agronomic traits in rice. We propose that editing of BR-related family genes could be a feasible approach for screening of desired plants to meet different requirements. Release of these materials as well as the related information also provides valuable resources for further BR research and utilization.
Assuntos
Brassinosteroides/metabolismo , Edição de Genes , Genoma de Planta , Oryza/genética , Proteínas de Plantas/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Forced-air warming (FAW) is an effective method of preventing inadvertent perioperative hypothermia (IPH). However, its warming effects can be influenced by the style and position of the FAW blanket. This study aimed to compare the effects of underbody FAW blankets being placed under or over patients in preventing IPH. METHODS: Patients (n=100) undergoing elective arthroscopic shoulder surgery in the lateral decubitus position were randomized into either under body (UB) group or the over body (OB) group (50 per group). The body temperature of the patients was recorded from baseline to the end of anesthesia. The incidences of postoperative hypothermia and shivering were also collected. RESULTS: A steady decline in the body temperature was observed in both groups up to 60 minutes after the start of FAW. After 60 minutes of warming, the OB group showed a gradual increase in the body temperature. However, the body temperature still decreased in UB group until 75 minutes, with a low of 35.7â ± 0.4â. Then the body temperature increased mildly and reached 35.8â ± 0.4â at 90 minutes. After 45 minutes of warming, the body temperature between the groups was significantly different (P < 0.05). The incidence of postoperative hypothermia in the UB group was significantly higher than that in the OB group (P = 0.023). CONCLUSIONS: The body temperature was significantly better with the use of underbody FAW blankets placed over patients than with them placed under patients. However, there was not a clinically significant difference in body temperature. The incidence of postoperative hypothermia was much lower in the OB group. Therefore, placing underbody FAW blankets over patients is recommended for the prevention of IPH in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 13/1/2021 with the registration number ChiCTR2100042071 . It was conducted from 14/1/2021 to 30/10/2021 as a single, blinded trial in Sichuan Provincial Orthopedic Hospital.
Assuntos
Hipotermia , Roupas de Cama, Mesa e Banho/efeitos adversos , Temperatura Corporal , Humanos , Hipotermia/etiologia , Hipotermia/prevenção & controle , Estudos Prospectivos , Ombro/cirurgiaRESUMO
Japonica/geng and indica/xian are two major rice (Oryza sativa) subspecies with multiple divergent traits, but how these traits are related and interact within each subspecies remains elusive. Brassinosteroids (BRs) are a class of steroid phytohormones that modulate many important agronomic traits in rice. Here, using different physiological assays, we revealed that japonica rice exhibits an overall lower BR sensitivity than indica. Extensive screening of BR signaling genes led to the identification of a set of genes distributed throughout the primary BR signaling pathway with divergent polymorphisms. Among these, we demonstrate that the C38/T variant in BR Signaling Kinase2 (OsBSK2), causing the amino acid change P13L, plays a central role in mediating differential BR signaling in japonica and indica rice. OsBSK2L13 in indica plays a greater role in BR signaling than OsBSK2P13 in japonica by affecting the auto-binding and protein accumulation of OsBSK2. Finally, we determined that OsBSK2 is involved in a number of divergent traits in japonica relative to indica rice, including grain shape, tiller number, cold adaptation, and nitrogen-use efficiency. Our study suggests that the natural variation in OsBSK2 plays a key role in the divergence of BR signaling, which underlies multiple divergent traits between japonica and indica.
Assuntos
Oryza , Brassinosteroides/metabolismo , Oryza/metabolismo , Fenótipo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismoRESUMO
Most characterized plant resistance proteins belong to the nucleotide-binding domain and Leu-rich repeat-containing (NLR) family. NLRs are present in an auto-inhibited state in the absence of specific pathogens, while gain-of-function mutations in NLRs usually cause autoimmunity. Here, we show that a gain-of-function mutation, weaker defense (wed), which caused a Phe-to-Leu substitution in the nucleotide-binding domain of a typical NLR in rice (Oryza sativa), led to enhanced susceptibility to Xanthomonas oryzae pv. Oryzae The unexpected accumulation of salicylic acid (SA), along with downregulation of NONEXPRESSOR OF PR1 (NPR1), in wed indicates the potential presence of a feedback regulation loop of SA biosynthesis in rice. Epistasis analyses illustrated that SA accumulation and the NLR-associated components RAR1, OsRac1, and PhyB are dispensable for the wed phenotypes. Intriguingly, besides pattern-triggered immunity, effector-triggered immunity conferred by different resistance proteins, including Xa3/Xa26, Xa4, and Xa21, was also disturbed by wed to a certain extent, indicating the existence of shared regulatory mechanisms for various defense systems. The identification of wed therefore provides a unique system for genetic dissection of shared immune signaling pathways activated by different types of immune receptors.
Assuntos
Oryza/metabolismo , Oryza/microbiologia , Proteínas de Plantas/metabolismo , Proteínas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Repetições Ricas em Leucina , Mutação/genética , Oryza/genética , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas/genética , Xanthomonas/patogenicidadeRESUMO
Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H2O2 to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H2O2 significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p < 0.05, H2O2 vs. Control). Dex preconditioning alleviated these injuries induced by H2O2. Dex preconditioning significantly increased expression of protein HO-1 and decreased expressions of proteins RIPK1 and RIPK3 induced by H2O2, while all these protective effects of Dex were reversed by YOH (all p < 0.05, Dex + H2O2 vs. H2O2; and YOH + Dex + H2O2 vs. Dex + H2O2). However, YOH did not prevent this protective effect of Dex against H2O2 induced apoptosis (YOH + Dex + H2O2 vs. Dex + H2O2, p > 0.05). These findings indicated that Dex attenuates H2O2 induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.
Assuntos
Dexmedetomidina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dexmedetomidina/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Necroptose/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Receptores Adrenérgicos/metabolismo , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
One of the major challenges associated with fuel cells is exploring highly efficient and low-cost electrocatalysts for the oxygen reduction reaction (ORR). Herein, the feasibility of using Ti3C2 MXene nanoparticles (NPs) to enhance the electrocatalytic activity of g-C3N4 for ORR was investigated. By varying the content of Ti3C2 NPs, a series of g-C3N4/Ti3C2 heterostructures were obtained, displaying enhanced electrocatalytic activity, including a positive shift in both onset and peak potentials toward ORR, compared to the original g-C3N4 in basic solution. We attribute the improvement to the favorable electrical conductivity of well-dispersed Ti3C2 MXene nanoparticles and also enhanced O2 adsorption due to the electronic coupling effect between g-C3N4 and Ti3C2 in the heterostructures. This work demonstrates the potential of earth-abundant MXene family materials to construct low-cost and high-performance electrocatalysts.
RESUMO
Objectives: Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice. Materials and Methods: Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured. Results: CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis. Conclusion: Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.
RESUMO
Crop yield potential is constrained by the inherent trade-offs among traits such as between grain size and number. Brassinosteroids (BRs) promote grain size, yet their role in regulating grain number is unclear. By deciphering the clustered-spikelet rice germplasm, we show that activation of the BR catabolic gene BRASSINOSTEROID-DEFICIENT DWARF3 (BRD3) markedly increases grain number. We establish a molecular pathway in which the BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 phosphorylates and stabilizes OsMADS1 transcriptional factor, which targets TERMINAL FLOWER1-like gene RICE CENTRORADIALIS2. The tissue-specific activation of BRD3 in the secondary branch meristems enhances panicle branching, minimizing negative effects on grain size, and improves grain yield. Our study showcases the power of tissue-specific hormonal manipulation in dismantling the trade-offs among various traits and thus unleashing crop yield potential in rice.
Assuntos
Brassinosteroides , Grão Comestível , Oryza , Proteínas de Plantas , Brassinosteroides/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. The purpose of this study was to evaluate the efficacy and safety of several medications and recommend better drug treatments for adults with HCM. Methods: A review of PubMed, Embase, the Cochrane Controlled Register of Trials (CENTRAL), ClinicalTrials.gov and CNKI databases was conducted for studies on the efficacy and safety of drugs for adults with HCM. A frequentist random effects model was used in this network analysis. Results: This network meta-analysis included 7 studies assessing seven medications, 6 studies evaluating monotherapy and 1 study evaluating combination therapy. Based on the network meta-analysis results, xiaoxinbi formula plus metoprolol (MD -56.50% [-72.43%, -40.57%]), metoprolol (MD -47.00% [-59.07%, -34.93%]) and mavacamten (MD -34.50% [-44.75%, -24.25%]) significantly reduced the resting left ventricular outflow tract gradient (LVOTG) in comparison with placebo. Resting LVOTG could also be reduced with N-acetylcysteine (NAC). The incidence of adverse drug reactions was not significantly different between the placebo group and the treatment group. Conclusion: For adults with HCM, the top 4 treatments included xiaoxinbi formula plus metoprolol, metoprolol, mavacamten and NAC.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=374222], identifier [CRD42022374222].
RESUMO
Brassinosteroids (BRs) are a class of steroid hormones with great potential for use in crop improvement. De-repression is usually one of the key events in hormone signaling. However, how the stability of GSK2, the central negative regulator of BR signaling in rice (Oryza sativa), is regulated by BRs remains elusive. Here, we identify the U-box ubiquitin ligase TUD1 as a GSK2-interacting protein by yeast two-hybrid screening. We show that TUD1 is able to directly interact with GSK2 and ubiquitinate the protein. Phenotypes of the tud1 mutant are highly similar to those of plants with constitutively activated GSK2. Consistent with this finding, GSK2 protein accumulates in the tud1 mutant compared with the wild type. In addition, inhibition of BR synthesis promotes GSK2 accumulation and suppresses TUD1 stability. By contrast, BRs can induce GSK2 degradation but promote TUD1 accumulation. Furthermore, the GSK2 degradation process is largely impaired in tud1 in response to BR. In conclusion, our study demonstrates the role of TUD1 in BR-induced GSK2 degradation, thereby advancing our understanding of a critical step in the BR signaling pathway of rice.
Assuntos
Brassinosteroides , Oryza , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Oryza/genética , Oryza/metabolismo , Ligases/metabolismo , Ubiquitina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Timely programmed cell death (PCD) of the tapetum supplying nutrients to microspores is a prerequisite for normal pollen development. Here we identified a unique mutant of rice (Oryza sativa L.), pollen sterility (post), which showed aborted pollens accompanied with extra-large husks. Due to failure of timely PCD of tapetal cells, post exhibited abnormal pollen wall patterning and defective pollen grains. By map-based cloning, we identified a causal gene, POST, encoding a novel protein which is ubiquitously localized in cells. RNA in situ hybridization showed that POST is highly detected in the tapetum and microspores at stages 8 and 9. Transcriptome analysis indicated that POST could function as an important regulator of the metabolic process involved in tapetal PCD. Compared with wild-type rice, post mutant has an increased cell number resulting from elevated expression of cell cycle associated genes in grain husks. Overexpression of POST inhibits grain size in wild type, while appropriate expression of POST in post mutant can recover the seed fertility but has little effect on the large grains, illustrating that fine-tuning of POST expression could be a potential strategy for rice yield improvement. The connection between cell division and cell death conferred by POST provides novel insights into the understanding of the tapetal PCD process.
Assuntos
Infertilidade , Oryza , Apoptose/genética , Divisão Celular , Flores/genética , Regulação da Expressão Gênica de Plantas , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/metabolismoRESUMO
OBJECTIVE: We aimed to compare the early clinical efficacy of endoscopy-assisted transforaminal lumbar interbody fusion (Endo-TLIF) and traditional Open-TLIF in the treatment of lumbar disc herniation and lumbar instability. METHODS: Forty-six patients with lumbar disc herniation and lumbar instability admitted to the hospital were retrospectively studied from October 11, 2018 to October 11, 2020. Patients (including 17 males and 29 females) were randomly divided into Endo-TLIF and Open-TLIF groups according to the different surgical treatment. Parameters such as intraoperative blood loss, operation time, and intraoperative fluoroscopy time during the surgery as well as preoperative and postoperative lumbar lordosis angle and lumbar clearance height and related complications were recorded in detail. RESULTS: Endo-TLIF significantly reduced intraoperative blood loss and bleeding volume compared with traditional Open-TLIF. The incision length in the Endo-TLIF group was shorter than in the Open-TLIF group and the intraoperative fluoroscopy time was also shorter than in the Open-TLIF group. The bed rest time and hospital discharge time were shortened in Endo-TLIF surgery compared with traditional Open-TLIF surgery. The creatine kinase (CK) values of the Endo-TLIF group were lower than that of the Open-TLIF group on the 1st and 3rd day after operation. Although computed tomography images of the lumbar lordosis angle did not show a significant difference between the Endo-TLIF group (43.97 ± 8.91°) and Open-TLIF group (49.08 ± 9.42°), the visual analogue scale score and Oswestry dysfunction index of lower back pain in the Endo-TLIF group were significantly lower than in the Open-TLIF group at 1 month and half a year after surgery. Complications in the Endo-TLIF group, such as lower limb neurological dysfunction and diseases of the respiratory or urinary system, effectively improved compared with the Open-TLIF group. CONCLUSION: Endo-TLIF appears to be a safer and more effective option for the treatment of lumbar disc herniation and lumbar instability, with a shorter recovery time, less trauma, less bleeding, no need for postoperative drainage, and less iatrogenic injury.
Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Instabilidade Articular , Lordose , Fusão Vertebral , Masculino , Feminino , Humanos , Fusão Vertebral/métodos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Endoscopia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgiaRESUMO
Spinal cord injury (SCI) is a severely disabling central nervous system injury with complex pathological mechanisms that leads to sensory and motor dysfunction. The current treatment for SCI is aimed at symptomatic symptom relief rather than the pathological causes. Several studies have reported that signaling pathways play a key role in SCI pathological processes and neuronal recovery mechanisms. The PI3K/Akt signaling pathway is an important pathway closely related to the pathological process of SCI, and activation of this pathway can delay the inflammatory response, prevent glial scar formation, and promote neurological function recovery. Activation of this pathway can promote the recovery of neurological function after SCI by reducing cell apoptosis. Based on the role of the PI3K/Akt pathway in SCI, it may be a potential therapeutic target. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.
Assuntos
Fosfatidilinositol 3-Quinases , Traumatismos da Medula Espinal , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Gliose/patologia , Transdução de Sinais , Apoptose , Medula Espinal/metabolismoRESUMO
Plant hormone cytokinin signals through histidine-aspartic acid (H-D) phosphorelay to regulate plant growth and development. While it is well known that the phosphorelay involves histidine kinases, histidine phosphotransfer proteins (HPs), and response regulators (RRs), how this process is regulated by external components remains unknown. Here we demonstrate that protein phosphatase with kelch-like domains (PPKL1), known as a signaling component of steroid hormone brassinosteroid, is actually a cryptic inhibitor of cytokinin phosphorelay in rice (Oryza sativa). Mutation at a specific amino acid D364 of PPKL1 activates cytokinin response and thus enlarges grain size in a semi-dominant mutant named s48. Overexpression of PPKL1 containing D364, either with the deletion of the phosphatase domain or not, rescues the s48 mutant phenotype. PPKL1 interacts with OsAHP2, one of authentic HPs, and D364 resides in a region resembling the receiver domain of RRs. Accordingly, PPKL1 can utilize D364 to suppress OsAHP2-to-RR phosphorelay, whereas mutation of D364 abolishes the effect. This function of PPKL1 is independent of the phosphatase domain that is required for brassinosteroid signaling. Importantly, editing of the D364-residential region produces a diversity of semi-dominant mutations associated with variously increased grain sizes. Further screening of the edited plants enables the identification of two genotypes that confer significantly improved grain yield. Collectively, our study uncovers a noncanonical cytokinin signaling suppressor and provides a robust tool for seed rational design.