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Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediated synaptic instability and subsequent withdrawal symptoms.
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Interferon gama , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Linfócitos T Reguladores , Animais , Camundongos , Analgésicos Opioides/administração & dosagem , Interferon gama/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/patologiaRESUMO
NAC (NAM, ATAF1/2, and CUC2) family transcription factors are involved in several cellular processes, including responses to drought, salinity, cold, and submergence. However, whether or how certain NAC proteins regulate drought tolerance in rice (Oryza sativa) remain unclear. In this study, we show that over-expression of OsNAC78 enhanced rice resistance to drought treatment, whereas Osnac78 mutant plants were susceptible to drought stress. We further characterized the OsNAC78 interacting protein, named NAC78 interacting protein6 (OsNACIP6), and found that it conferred rice drought tolerance. Our results demonstrate that OsNACIP6 enhanced transcription of OsNAC78 and promoted the expression of its downstream target OsGSTU37, encoding a glutathione reductase. The ABRE4 cis-element in the promoter region of OsNACIP675-1-127 conferred significant up-regulation of OsNACIP6 expression and initiated the OsNACIP6/OsNAC78-OsGSTU37 module that facilitates rice growth under drought conditions. Together, our results uncover a transcriptional module composed of OsNACIP6, OsNAC78, and OsGSTU37 and provide insights into the molecular mechanisms underlying the drought stress response in rice.
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Although thousands of genes have been identified or cloned in rice (Oryza sativa) in the last two decades, the majority of them have only been separately characterized in specific varieties or single-gene modified backgrounds, thus limiting their practical application. We developed an optimized multiplex genome editing (MGE) toolbox that can efficiently assemble and stably express up to twelve sgRNA targets in a single plant expression vector. In this study, we established the MGE-based Rapid Directional Improvement (MRDI) strategy for directional improvement of complex agronomic traits in one small-scale rice transformation. This approach provides a rapid and practical procedure, encompassing sgRNA assembly, transgene-free screening and the creation of promising germplasm, by combining the precision of gene editing with phenotype-based field breeding. The MRDI strategy was used to generate the full diversity of twelve main agronomic genes in rice cultivar FXZ for the directional improvement of its growth duration and plant architecture. After applying the MRDI to FXZ, ideal plants with the desired traits of early heading date reduced plant height, and more effective panicles were generated without compromising yield, blast resistance and grain quality. Furthermore, the results of whole-genome sequencing (WGS), including the analysis of structural variations (SVs) and single nucleotide variations (SNVs) in the MGE plants, confirmed the high specificity and low frequency of unwanted mutations associated with this strategy. The MRDI breeding strategy would be a robust approach for exploring and applying crucial agronomic genes, as well as for generating novel elite germplasm in the future.
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Edição de Genes , Genoma de Planta , Oryza , Oryza/genética , Oryza/crescimento & desenvolvimento , Edição de Genes/métodos , Genoma de Planta/genética , Melhoramento Vegetal/métodos , Fenótipo , Sistemas CRISPR-Cas/genética , Plantas Geneticamente Modificadas/genéticaRESUMO
Opioid withdrawal generates extremely unpleasant physical symptoms and negative affective states. A rapid relief of opioid withdrawal-induced anxiety has obvious clinical relevance but has been rarely reported. We have shown that injection of ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) leads to a rapid alleviation of anxiety-like behaviors in male mice undergoing chronic morphine withdrawal. Here we investigated the contribution of nucleus accumbens shell (sNAc) parvalbumin (PV)-neurons to this process. Chronic morphine withdrawal was associated with higher intrinsic excitability of sNAc PV-neurons via reduced voltage-dependent potassium currents. Chemogenetic inhibition of sNAc PV-neurons reversed the enhanced excitability of PV-neurons and anxiety-like behaviors in these morphine withdrawal male mice, while activation of sNAc PV-neurons induced anxiety-like behaviors in naive male mice. (2R,6R)-HNK reversed the altered potassium currents and intrinsic excitability of sNAc PV-neurons. Our findings demonstrate an important contribution of sNAc PV-neurons to modulating morphine withdrawal-induced anxiety-like behaviors and rapid relief of anxiety-like behaviors by (2R,6R)-HNK, this newly identified target may have therapeutic potentials in treating opioid addiction and anxiety disorders.
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Ketamina , Masculino , Animais , Camundongos , Parvalbuminas , Morfina , Analgésicos Opioides , Núcleo Accumbens , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Transtornos de Ansiedade , Neurônios , PotássioRESUMO
BACKGROUND: Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy. METHODS: To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated. RESULTS: All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection. CONCLUSION: PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.
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Pancreaticoduodenectomia , Pancreaticojejunostomia , Humanos , Pancreaticojejunostomia/métodos , Pancreaticoduodenectomia/métodos , Anastomose Cirúrgica/métodos , Pâncreas/cirurgia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura/efeitos adversosRESUMO
This research presents a comprehensive study of the dichotomous search iterative parabolic discrete time Fourier transform (Ds-IpDTFT) estimator, a novel approach for fine frequency estimation in noisy exponential signals. The proposed estimator leverages a dichotomous search process before iterative interpolation estimation, which significantly reduces computational complexity while maintaining high estimation accuracy. An in-depth exploration of the relationship between the optimal parameter p and the unknown parameter δ forms the backbone of the methodology. Through extensive simulations and real-world experiments, the Ds-IpDTFT estimator exhibits superior performance relative to other established estimators, demonstrating robustness in noisy conditions and stability across varying frequencies. This efficient and accurate estimation method is a significant contribution to the field of signal processing and offers promising potential for practical applications.
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CONTEXT: Zhibai Dihuang pill (ZD), a traditional Chinese medicine nourishes Yin and reduces internal heat, is believed to have therapeutic effects on urinary tract infections (UTIs). OBJECTIVE: To explore the effects and mechanism of modified ZD (MZD) on UTI induced by extended-spectrum ß-lactamase (ESBLs) Escherichia coli. MATERIALS AND METHODS: Thirty Sprague-Dawley rats were randomly divided into control, model (0.5 mL 1.5 × 108 CFU/mL ESBLs E. coli), MZD (20 g/kg MZD), LVFX (0.025 g/kg LVFX), and MZD + LVFX groups (20 g/kg MZD + 0.025 g/kg LVFX), n = 6. After 14 days of treatment, serum biochemical indicators, renal function indicators, bladder and renal histopathology, and urine bacterial counts in rats were determined. Additionally, the effects of MZD on ESBLs E. coli biofilm formation and related gene expression were analyzed. RESULTS: MZD significantly decreased the count of white blood cells (from 13.12 to 9.13), the proportion of neutrophils (from 43.53 to 23.18), C-reactive protein (from 13.21 to 9.71), serum creatinine (from 35.78 to 30.15), and urea nitrogen (from 12.56 to 10.15), relieved the inflammation and fibrosis of bladder and kidney tissues, and reduced the number of bacteria in urine (from 2174 to 559). In addition, MZD inhibited the formation of ESBLs E. coli biofilms (2.04-fold) and decreased the gene expressions of luxS, pfS and ompA (1.41-1.62-fold). DISCUSSION AND CONCLUSION: MZD treated ESBLs E. coli-induced UTI inhibited biofilm formation, providing a theoretical basis for the clinical application of MZD. Further study on the clinical effect of MZD may provide a novel therapy option for UTI.
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Antibacterianos , Medicamentos de Ervas Chinesas , Infecções Urinárias , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ratos Sprague-Dawley , Infecções Urinárias/induzido quimicamente , Infecções Urinárias/tratamento farmacológico , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Animais , Ratos , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
MAIN CONCLUSION: We identified a typical rice premature senescence leaf mutant 86 (psl86) and exhibited the first global ubiquitination data during rice leaf senescence. Premature leaf senescence affects the yield and quality of rice, causing irreparable agricultural economic losses. In this study, we reported a rice premature senescence leaf mutant 86 (psl86) in the population lines of rice (Oryza sativa) japonica cultivar 'Yunyin' (YY) mutagenized using ethyl methane sulfonate (EMS) treatment. Immunoblotting analysis revealed that a higher ubiquitination level in the psl86 mutant compared with YY. Thus, we performed the proteome and ubiquitylome analyses to identify the differential abundance proteins and ubiquitinated proteins (sites) related to leaf senescence. Among 885 quantified lysine ubiquitination (Kub) sites in 492 proteins, 116 sites in 94 proteins were classified as up-regulated targets and seven sites in six proteins were classified as down-regulated targets at a threshold of 1.5. Proteins with up-regulated Kub sites were mainly enriched in the carbon fixation in photosynthetic organisms, glycolysis/gluconeogenesis and the pentose phosphate pathway. Notably, 14 up-regulated Kub sites in 11 proteins were enriched in the carbon fixation in photosynthetic organism pathway, and seven proteins (rbcL, PGK, GAPA, FBA5, ALDP, CFBP1 and GGAT) were down-regulated, indicating this pathway is tightly regulated by ubiquitination during leaf senescence. To our knowledge, we present the first global data on ubiquitination during rice leaf senescence.
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Oryza , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Senescência Vegetal , ProteomaRESUMO
Lead-free double perovskite materials with efficient and stable self-trapped exciton (STE) emissions show enormous potential for next-generation solid-state lighting. However, the low-emission efficiency and difficulty of spectral regulation are two major obstacles to their application. Here, all-inorganic rare-earth-based double perovskite Cs2NaYCl6 single crystals with strong blue emissions were reported as effective hosts to accommodate lanthanide ion doping. By controlling the introduction of Tb3 + ions and efficient energy transfer from the STEs to the dopants, the emission color of Cs2NaYCl6 single crystals was flexibly modulated from blue to green. The quantum yields were also significantly improved from 10% to 78.81% by optimizing the Tb3 + ion concentration. Further, stable light-emitting diode prototypes based on Cs2NaYCl6 color conversion materials were fabricated to demonstrate the practical applications of rare-earth-based double perovskite.
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Rapid and automated detection of acute myocardial infarction (AMI) at its developing stage is very important due to its high mortality rate. To quantitatively diagnose AMI, Myo, CK-MB, and cTnI are chosen as three biomarkers, which are usually detected through an immunosorbent assay, such as the enzyme-linked immunosorbent assay. However, the approach poses many drawbacks, such as long detection time, the cumbersome process, the need for professionals, and the difficulty of realizing automatic operation. Here, a multichannel digital microfluidic (DMF) thermal control chip integrated with a sandwich-based immunoassay strategy is proposed for the automated, rapid, and sensitive detection of AMI biomarkers. A miniaturized temperature control module is integrated on the back of the DMF chip, meeting the temperature requirement for the immunoassay. With this DMF thermal control chip, sample and reagent consumption are reduced to several microliters, significantly alleviating reagent consumption and sample dependence, and the automated and multichannel detection of biomarkers can be achieved. In this work, the simultaneously noninvasive detection of the human serum sample containing the three biomarkers of AMI is also achieved within 30 min, which improves the diagnostic accuracy of AMI. Due to the features of automation and miniaturization, the multichannel immunosensor can be used in community hospitals to increase the speed of diagnosis of patients with various acute diseases.
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Técnicas Biossensoriais , Infarto do Miocárdio , Biomarcadores , Creatina Quinase Forma MB , Humanos , Imunoensaio , Microfluídica , Infarto do Miocárdio/diagnósticoRESUMO
BACKGROUND: Phosphoenolpyruvate carboxylase (PEPC) plays an important role in the primary metabolism of higher plants. Several studies have revealed the critical importance of PEPC in the interaction of carbon and nitrogen metabolism. However, the function mechanism of PEPC in nitrogen metabolism is unclear and needs further investigation. RESULTS: This study indicates that transgenic rice expressing the sugarcane C4-PEPC gene displayed shorter primary roots and fewer crown roots at the seedling stage. However, total nitrogen content was significantly higher in transgenic rice than in wild type (WT) plants. Proteomic analysis revealed that there were more differentially expressed proteins (DEPs) responding to nitrogen changes in transgenic rice. In particular, the most enriched pathway "glutathione (GSH) metabolism", which mainly contains GSH S-transferase (GST), was identified in transgenic rice. The expression of endogenous PEPC, GST and several genes involved in the TCA cycle, glycolysis and nitrogen assimilation changed in transgenic rice. Correspondingly, the activity of enzymes including GST, citrate synthase, 6-phosphofructokinase, pyruvate kinase and ferredoxin-dependent glutamate synthase significantly changed. In addition, the levels of organic acids in the TCA cycle and carbohydrates including sucrose, starch and soluble sugar altered in transgenic rice under different nitrogen source concentrations. GSH that the substrate of GST and its components including glutamic acid, cysteine and glycine accumulated in transgenic rice. Moreover, the levels of phytohormones including indoleacetic acid (IAA), zeatin (ZT) and isopentenyladenosine (2ip) were lower in the roots of transgenic rice under total nutrients. Taken together, the phenotype, physiological and biochemical characteristics of transgenic rice expressing C4-PEPC were different from WT under different nitrogen levels. CONCLUSIONS: Our results revealed the possibility that PEPC affects nitrogen metabolism through regulating GST, which provide a new direction and concepts for the further study of the PEPC functional mechanism in nitrogen metabolism.
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Glutationa Transferase/metabolismo , Nitrogênio/metabolismo , Oryza/enzimologia , Fosfoenolpiruvato Carboxilase/metabolismo , Saccharum/enzimologia , Carbono/metabolismo , Oryza/genética , Oryza/metabolismo , Fosfoenolpiruvato Carboxilase/genética , Plantas Geneticamente Modificadas , Proteômica , Saccharum/genética , TranscriptomaRESUMO
Here, Tb3+ ions are incorporated into Cs2Ag0.6Na0.4InCl6:Bi double perovskite microcrystals via a re-crystallization method. Tb3+ ions doping not only makes the white light spectrum adjustable, but also maintains the high photoluminescence quantum yield (PLQY). The optimal value of PLQY is 95%. These are comparable to the current highest values. Noteworthy is that, intrinsic emission of Tb3+ ions is attributed to the effective energy transfer from the trapped exciton state of the double perovskite host to Tb3+ ions. Finally, mixing 30% Tb3+ alloyed Cs2Ag0.6Na0.4InCl6:Bi and Cs2NaInCl6:10%Sb phosphors, a series of double-perovskite-based white light-emitting diodes (WLEDs) are prepared. The color coordinates of the best WLEDs are (0.34, 0.32), the lumen efficiency is 42 lm/W, and the color rendering index is 94.3. It is worth mentioning here that there is no blue light loss caused by energy reabsorption between the two phosphors, because the excitation wavelengths of the two phosphors are concentrated in the ultraviolet band. This work provides a new strategy for preparing high-performance WLED.
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Here, composites including highly efficient inert shell-modified NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles (UCNPs) and CsPbI3 perovskite quantum dots (PQDs) have been successfully synthesized by the assistance of (3-aminopropyl)triethoxysilane (APTES) as a precursor for a SiO2 matrix. UCNPs and CsPbI3 PQDs in this composite structure show excellent stability in ambient conditions. Importantly, the efficient UC emission of CsPbI3 PQDs was realized, which means that the single red emission of inert shell-modified UCNPs can be easily obtained by depending on these composite structures. Furthermore, the single red emission wavelength can be easily regulated from 705 to 625 nm by introducing appropriate proportion of Br- ions, which is very difficult to achieve for traditional UCNPs. Moreover, benefiting from the efficient downshifting (DS) red emission of CsPbI3 PQDs, the composites possess the dual-wavelength excitation characteristics. So, the excellent dual-mode anticounterfeiting application has been demonstrated. This work will provide a new idea for the development of perovskite-based multifunctional materials.
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Trivalent praseodymium (Pr3+)-doped materials have been extensively used in high-resolution laser spectroscopy, owing to their outstanding conversion efficiencies of plentiful transitions in the visible laser region. However, to clarify the microstructure and energy transfer mechanism of Pr3+-doped host crystals is a challenging topic. In this work, the stable structures of Pr3+-doped yttrium orthoaluminate (YAlO3) have been widely searched based on the CALYPSO method. A novel monoclinic structure with the Pm group symmetry is successfully identified. The Pr3+ impurity can precisely occupy the Y3+ position and get incorporated into the YAlO3 (YAP) host crystal with a Pr3+ concentration of 6.25%. The result of the electronic band structure reveals a 3.62 eV band gap, which suggests a semiconductor character of YAP:Pr. Using our developed well-established parametrization matrix diagonalization (WEPMD) method, we have systematically analyzed the energy level scheme and proposed a set of newly improved parameters. Additionally, the energy transfer mechanism of YAP:Pr is clarified by deciphering the numerical electric dipole and magnetic dipole transitions. The popular red emission at 653 nm is assigned to the transition 3P0 â 3F2, while the transition 3P0 â 3H4 with a large branching ratio is predicted to be a good laser channel. Many promising emission lines for laser actions are also obtained in the visible light region. Our results not only provide important insights into the energy transfer mechanisms of rare-earth ion-doped materials but also pave the way for the implementation of new types of laser devices.
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Drug relapse among addicts often occurs due to the learned association between drug-paired cues and the rewarding effects of these drugs, such as morphine. Contextual memory associated with morphine has a central role in maintenance and relapse. We showed that morphine-conditioned place preference (CPP) activates extracellular-regulated protein kinase (ERK) in the nucleus accumbens (NAc). The main enzymes that mediate ERK dephosphorylation are members of the dual-specificity phosphatase (DUSP) superfamily. It is unclear which members regulate the morphine CPP-induced activation of ERK. After screening, DUSP15 was found to be decreased during both morphine CPP expression and the reinstatement period. Intra-NAc infusions of AAV-DUSP15 (overexpression) not only prevented the expression of morphine-induced CPP but also facilitated extinction, inhibited reinstatement, and abolished ERK activation. However, after repeated morphine exposure and withdrawal in mice, there was no change in the expression of p-ERK and DUSP15, and the overexpression of DUSP15 in the NAc did not improve the impaired spatial memory or anxiety-like behaviour induced by morphine. Together, these findings indicate that DUSP15 not only prevents the expression of drug-paired contextual memory but also promotes the extinction of existing addiction memories, thus providing a novel therapeutic target for the treatment of drug addiction.
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Fosfatases de Especificidade Dupla/metabolismo , Memória/efeitos dos fármacos , Morfina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Sinais (Psicologia) , Extinção Psicológica/efeitos dos fármacos , Masculino , Camundongos , RecompensaRESUMO
Self-powered piezoelectric sensor can achieve real-time and harmless monitoring of motion processes without external power supply, which can be attached on body skin or joints to detect human motion and powered by mechanical energy. Here, a sensor for monitoring emergent motion is developed using the PVDF as active material and piezoelectric output as sensing signal. The multi-point control function enables the sensor to monitor the sequence of force order, angle change, and motion frequency of the "elbow lift, arm extension, and wrist compression" during shooting basketball. In addition, the sensor shows can simultaneously charge the capacitor to provide more power for intelligence, typically Bluetooth transmission. The sensor shows good performance in other field, such as rehabilitation monitoring and speech input systems. Therefore, the emerging application of flexible sensors have huge long-term prospects in sport big data collection and Internet of Things (IoT).
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Basquetebol , Fontes de Energia Elétrica , Humanos , Monitorização Fisiológica , Movimento (Física)RESUMO
BACKGROUND: Low temperature is a major factor influencing the growth and development of Chinese jujube (Ziziphus jujuba Mill.) in cold winter and spring. Little is known about the molecular mechanisms enabling jujube to cope with different freezing stress conditions. To elucidate the freezing-related molecular mechanism, we conducted comparative transcriptome analysis between 'Dongzao' (low freezing tolerance cultivar) and 'Jinsixiaozao' (high freezing tolerance cultivar) using RNA-Seq. RESULTS: More than 20,000 genes were detected at chilling (4 °C) and freezing (- 10 °C, - 20 °C, - 30 °C and - 40 °C) stress between the two cultivars. The numbers of differentially expressed genes (DEGs) between the two cultivars were 1831, 2030, 1993, 1845 and 2137 under the five treatments. Functional enrichment analysis suggested that the metabolic pathway, response to stimulus and catalytic activity were significantly enriched under stronger freezing stress. Among the DEGs, nine participated in the Ca2+ signal pathway, thirty-two were identified to participate in sucrose metabolism, and others were identified to participate in the regulation of ROS, plant hormones and antifreeze proteins. In addition, important transcription factors (WRKY, AP2/ERF, NAC and bZIP) participating in freezing stress were activated under different degrees of freezing stress. CONCLUSIONS: Our research first provides a more comprehensive understanding of DEGs involved in freezing stress at the transcriptome level in two Z. jujuba cultivars with different freezing tolerances. These results may help to elucidate the molecular mechanism of freezing tolerance in jujube and also provides new insights and candidate genes for genetically enhancing freezing stress tolerance.
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Ziziphus/metabolismo , Resposta ao Choque Frio , Congelamento , Galactose/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genes de Plantas/fisiologia , Redes e Vias Metabólicas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Ziziphus/genética , Ziziphus/fisiologiaRESUMO
BACKGROUND: Rice ratooning has traditionally been an important component of the rice cropping system in China. However, compared with the rice of the first harvest, few studies on factors effecting ratoon rice yield have been conducted. Because ratoon rice is a one-season rice cultivated using axillary buds that germinate on rice stakes and generate panicles after the first crop's harvest, its production is mainly affected by the growth of axillary buds. The objectives of this study were to evaluate the sprouting mechanism of axillary buds to improve the ratoon rice yield. RESULTS: First, we observed the differentiation and growth dynamics of axillary buds at different nodes of Shanyou 63, and found that they differentiated from bottom to top before the heading of the mother stem, and that they developed very slowly. After heading they differentiated from top to bottom, and the ones on the top, especially the top 2nd node, developed much faster than those at the other nodes. The average length and dry weight of the axillary buds were significantly greater than those at other nodes by the yellow ripe stage, and they differentiated into pistils and stamens by 6 d after the yellow ripe stage. The morphology of vegetative organs from regenerated tillers of Shanyou 63 also suggested the superior growth of the upper buds, which was regulated by hormones, in ratoon rice. Furthermore, a comprehensive proteome map of the rice axillary buds at the top 2nd node before and after the yellow ripe stage was established, and some proteins involved in steroid biosynthesis were significantly increased. Of these, four took part in brassinosteroid (BR) biosynthesis. Thus, BR signaling may play a role in the germination of axillary buds of ratoon rice. CONCLUSIONS: The data provide insights into the molecular mechanisms underlying BR signaling, and may allow researchers to explore further the biological functions of endogenous BRs in the germination of axillary buds of ratoon rice.
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Brassinosteroides/metabolismo , Flores/fisiologia , Germinação , Oryza/fisiologia , Transdução de SinaisRESUMO
DCC netrin 1 receptor (DCC) affects the structure and function of the dopamine circuitry, which in turn affects the susceptibility to developing addiction. In a previous study, we found that single nucleotide polymorphism (SNP) rs12607853 in the 3' untranslated region (3'-UTR) of DCC was significantly associated with heroin addiction. In the current study, we first used bioinformatics prediction to identify the DCC rs12607853 C allele as a potential hsa-miR-422a and hsa-miR-378c target site. We then used vector construction and dual-luciferase reporter assays to investigate the targeting relationship of DCC rs12607853 with hsa-miR-422a and hsa-miR-378c. The dual-luciferase reporter gene assay confirmed that the C allele of rs12607853 in combination with hsa-miR-422a led to repressed dual-luciferase gene expression. Moreover, gene expression assays disclosed that hsa-miR-422a inhibited DCC expression at both the mRNA and protein levels. We also found that morphine inhibited the expression of hsa-miR-422a but increased the expression of DCC mRNA, and this change in the expression of hsa-miR-422a could not be reversed by naloxone, which suggested that the role of DCC in opioid addiction might be regulated by hsa-miR-422a. In summary, this study improves our understanding of the role of hsa-miR-422a and identifies the genetic basis of rs12607853, which might contribute to the discovery of new biomarkers or therapeutic targets for opioid addiction.
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Receptor DCC/genética , Receptor DCC/metabolismo , Regulação para Baixo , Dependência de Heroína/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Biologia Computacional/métodos , Regulação para Baixo/efeitos dos fármacos , Células HEK293 , Humanos , Morfina/farmacologia , Naloxona/farmacologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. METHODS: A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. RESULTS: We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. CONCLUSIONS: Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.