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The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.
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Brassicaceae , Flores , Regulação da Expressão Gênica de Plantas , Brassicaceae/genética , Brassicaceae/fisiologia , Produtos Agrícolas/genética , Flores/genética , Flores/fisiologia , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Fenômenos Fisiológicos Vegetais , Mapeamento Cromossômico , MutaçãoRESUMO
Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.
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The electrochemical N2 reduction reaction (NRR) is a green and energy-saving sustainable technology for NH3 production. However, high activity and high selectivity can hardly be achieved in the same catalyst, which severely restricts the development of the electrochemical NRR. In2Se3 with partially occupied p-orbitals can suppress the H2 evolution reaction (HER), which shows excellent selectivity in the electrochemical NRR. The presence of VIn can simultaneously provide active sites and confine Re clusters through strong charge transfer. Additionally, well-isolated Re clusters stabilized on In2Se3 by the confinement effect of VIn result in Re-VIn active sites with maximum availability. By combining Re clusters and VIn as dual sites for spontaneous N2 adsorption and activation, the electrochemical NRR performance is enhanced significantly. As a result, the Re-In2Se3-VIn/CC catalyst delivers a high NH3 yield rate (26.63 µg h-1 cm-2) and high FEs (30.8%) at -0.5 V vs RHE.
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Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2â¢-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2â¢-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.
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Aterosclerose , Cicloexilaminas , Ferroptose , Fenilenodiaminas , Animais , Camundongos , Humanos , Fosfolipídeos , Fosforilcolina , Éteres Fosfolipídicos/metabolismo , Éteres Fosfolipídicos/farmacologia , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Proteína 3 Ligante de Ácido GraxoRESUMO
The SnRK (sucrose non-fermentation-related protein kinase) plays an important role in regulating various signals in plants. However, as an important bamboo shoot and wood species, the response mechanism of PheSnRK in Phyllostachys edulis to hormones, low energy and stress remains unclear. In this paper, we focused on the structure, expression, and response of SnRK to hormones and sugars. In this study, we identified 75 PheSnRK genes from the Moso bamboo genome, which can be divided into three groups according to the evolutionary relationship. Cis-element analysis has shown that the PheSnRK gene can respond to various hormones, light, and stress. The PheSnRK2.9 proteins were localized in the nucleus and cytoplasm. Transgenic experiments showed that overexpression of PheSnRK2.9 inhibited root development, the plants were salt-tolerant and exhibited slowed starch consumption in Arabidopsis in the dark. The results of yeast one-hybrid and dual luciferase assay showed that PheIAAs and PheNACs can regulate PheSnRK2.9 gene expression by binding to the promoter of PheSnRK2.9. This study provided a comprehensive understanding of PheSnRK genes of Moso bamboo, which provides valuable information for further research on energy regulation mechanism and stress response during the growth and development of Moso bamboo.
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Arabidopsis , Poaceae , Poaceae/genética , Evolução Biológica , Bioensaio , Saccharomyces cerevisiae , HormôniosRESUMO
The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.
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Actinidia , Proteínas de Homeodomínio , Proteínas de Homeodomínio/genética , Genoma de Planta , Filogenia , Actinidia/genética , Zíper de Leucina/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Perfilação da Expressão GênicaRESUMO
Development of new near-infrared fluorophores is one of the eternal themes in the field of biosensing and biological imaging. In this work, we constructed a novel fluorophore platform MOR by replacing methylindole of hemicyanine fluorophore (CyR) with benzoxazole to acquire better fluorescence characteristics. Based on the platform, a near infrared (NIR) fluorescent probe MOR-CES2 was synthesized for the specific "off-on" response to carboxylesterase 2 (CES2). The probe exhibited excellent properties including near-infrared emission (735 nm), large Stokes shift (105 nm), high sensitivity (LOD, 0.3 ng/mL), and rapid response (15 min). The successful application of MOR-CES2 in biological imaging of CES2 in mice with thyroid cancer and inflammatory bowel disease demonstrated that the probe could identify cancer cells and tissues and sensitively respond to inflammation. The results proved the potency of MOR-CES2 as an efficient imaging tool to assist in the surgical resection of CES2-related tumors.
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Corantes Fluorescentes , Neoplasias da Glândula Tireoide , Camundongos , Animais , Imagem Óptica/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Raios InfravermelhosRESUMO
The assessment of consciousness states, especially distinguishing minimally conscious states (MCS) from unresponsive wakefulness states (UWS), constitutes a pivotal role in clinical therapies. Despite that numerous neural signatures of consciousness have been proposed, the effectiveness and reliability of such signatures for clinical consciousness assessment still remains an intense debate. Through a comprehensive review of the literature, inconsistent findings are observed about the effectiveness of diverse neural signatures. Notably, the majority of existing studies have evaluated neural signatures on a limited number of subjects (usually below 30), which may result in uncertain conclusions due to small data bias. This study presents a systematic evaluation of neural signatures with large-scale clinical resting-state electroencephalography (EEG) signals containing 99 UWS, 129 MCS, 36 emergence from the minimally conscious state, and 32 healthy subjects (296 total) collected over 3 years. A total of 380 EEG-based metrics for consciousness detection, including spectrum features, nonlinear measures, functional connectivity, and graph-based measures, are summarized and evaluated. To further mitigate the effect of data bias, the evaluation is performed with bootstrap sampling so that reliable measures can be obtained. The results of this study suggest that relative power in alpha and delta serve as dependable indicators of consciousness. With the MCS group, there is a notable increase in the phase lag index-related connectivity measures and enhanced functional connectivity between brain regions in comparison to the UWS group. A combination of features enables the development of an automatic detector of conscious states.
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Estado de Consciência , Vigília , Humanos , Reprodutibilidade dos Testes , Benchmarking , Eletroencefalografia , Estado Vegetativo PersistenteRESUMO
The self-healing ability of superhydrophobic surfaces in air has attracted tremendous additions in recent years. Once the superhydrophobic surface is damaged underwater, water seeps into gaps among micro/nano structures. The air film diffuses into water and eventually disappears during immersion without actively replenishing the gas, which results in the impossible of self-healing. Here, an underwater self-healing superhydrophobic coating with the synergetic effect of hydrogen bonds and self-formed bubbles via the spraying method is fabricated. The movement of hydrogen bonds of the prepared polyurethane enables microstructures to reconstruct at room temperature and self-formed bubbles of effervescent materials underwater actively replenish gas before microstructures completely self-healing, achieving the self-healing property of the superhydrophobic coating. Moreover, the hydrophilic effervescent material is sprayed along with unmodified micron-scaled particles because modified nano-scale particles are key factors for the realization of superhydrophobic coating. An underwater stable superhydrophobic surface with pressure resistance (4.9 kPa) is demonstrated. This superhydrophobic coating also shows excellent drag reduction, anti-icing, and anti-corrosion properties. This facile and scalable method offers a new route that an underwater self-healing superhydrophobic coating executes the gas film recovery.
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The practical application of aqueous zinc (Zn) metal batteries (ZMBs) is hindered by the complicated hydrogen evolution, passivation reactions, and dendrite growth of Zn metal anodes. Here, an ion-pumping quasi-solid electrolyte (IPQSE) with high Zn2+ transport kinetics enabled by the electrokinetic phenomena to realize high-performance quasi-solid state Zn metal batteries (QSSZMBs) is reported. The IPQSE is prepared through the in situ ring-opening polymerization of tetramethylolmethane-tri-ß-aziridinylpropionate in the aqueous electrolyte. The porous polymer framework with high zeta potential provides the IPQSE with an electrokinetic ion-pumping feature enabled by the electrokinetic effects (electro-osmosis and electrokinetic surface conduction), which significantly accelerates the Zn2+ transport, reduces the concentration polarization and overcomes the diffusion-limited current. Moreover, the Zn2+ affinity of the polymer and hydrogen bonding interactions in the IPQSE changes the Zn2+ coordination environment and reduces the amount of free H2O, which lowers the H2O activity and inhibits H2O-induced side reactions. Consequently, the highly reversible and stable Zn metal anodes are achieved. The assembled QSSZMBs based on the IPQSE display excellent cycling stability with high capacity retention and Coulombic efficiency. The high-performance quasi-solid state Zn metal pouch cells are demonstrated, showing great promise for the practical application of the IPQSE.
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Hydrogen peroxide (H2O2) is a highly value-added and environmental-friendly chemical with various applications. The production of H2O2 by electrocatalytic 2e- oxygen reduction reaction (ORR) has emerged as a promising alternative to the energy-intensive anthraquinone process. High selectivity Catalysts combining with superior activity are critical for the efficient electrosynthesis of H2O2. Earth-abundant transition metal selenides (TMSs) being discovered as a classic of stable, low-cost, highly active and selective catalysts for electrochemical 2e- ORR. These features come from the relatively large atomic radius of selenium element, the metal-like properties and the abundant reserves. Moreover, compared with the advanced noble metal or single-atom catalysts, the kinetic current density of TMSs for H2O2 generation is higher in acidic solution, which enable them to become suitable catalyst candidates. Herein, the recent progress of TMSs for ORR to H2O2 is systematically reviewed. The effects of TMSs electrocatalysts on the activity, selectivity and stability of ORR to H2O2 are summarized. It is intended to provide an insight from catalyst design and corresponding reaction mechanisms to the device setup, and to discuss the relationship between structure and activity.
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BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.
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BACKGROUND: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. METHODS: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. RESULTS: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). CONCLUSIONS: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes.
We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality.
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Aterosclerose , Biomarcadores , Causas de Morte , HDL-Colesterol , Diabetes Mellitus , Triglicerídeos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Medição de Risco , Biomarcadores/sangue , Aterosclerose/mortalidade , Aterosclerose/sangue , Aterosclerose/diagnóstico , Fatores de Risco , Fatores de Tempo , Adulto , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , HDL-Colesterol/sangue , Estados Unidos/epidemiologia , Triglicerídeos/sangue , Prognóstico , Neoplasias/mortalidade , Neoplasias/sangue , Neoplasias/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnósticoRESUMO
BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.
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Radiômica , Neoplasias Gástricas , Humanos , Estudos de Coortes , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Instabilidade de Microssatélites , Imunoterapia , Tomografia Computadorizada por Raios X , ImunoglobulinasRESUMO
KEY MESSAGE: A stable Agrobacterium-mediated transformation system was constructed for B. juncea, and BjuLKP2 was overexpressed, leading to plant yellowing. A stable and efficient transformation system is necessary to verify gene functions in plants. To establish an Agrobacterium-mediated transformation system for B. juncea, various factors, including the explant types, hormone combination and concentration, infection time and concentration, were optimized. Eventually, a reliable system was established, and two BjuLKP2 overexpression (OE) lines, which displayed yellowing of cotyledons, shoot tips, leaves and flower buds, as well as a decrease in total chlorophyll content, were generated. qRT-PCR assays revealed significant upregulation of five chlorophyll synthesis genes and downregulation of one gene in the BjuLKP2 OE line. Furthermore, antioxidant capacity assays revealed reduced activities of APX, CAT and SOD, while POD activity increased in the BjuLKP2 OE26. Additionally, the kinetic determination of chlorophyll fluorescence induction suggested a decrease in the photosynthetic ability of BjuLKP2 OE26. GUS assays revealed the expression of BjuLKP2 in various tissues, including the roots, hypocotyls, cotyledons, leaf vasculature, trichomes, sepals, petals, filaments, styles and stigma bases, but not in seeds. Scanning electron revealed alterations in chloroplast ultrastructure in both the sponge and palisade tissue. Collectively, these findings indicate that BjuLKP2 plays a role in plant yellowing through a reduction in chlorophyll content and changes in chloroplasts structure.
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Clorofila , Regulação da Expressão Gênica de Plantas , Mostardeira , Plantas Geneticamente Modificadas , Transformação Genética , Clorofila/metabolismo , Mostardeira/genética , Folhas de Planta/genética , Fotossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Agrobacterium/genéticaRESUMO
Cantu syndrome (CS) (OMIM #239850) is an autosomal dominant multiorgan system condition, associated with a characteristic facial phenotype, hypertrichosis, and multiple cardiovascular complications. CS is caused by gain-of-function (GOF) variants in KCNJ8 or ABCC9 that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (KATP) channels. A novel heterozygous ABCC9 variant, c.2440G>T; p.Gly814Trp, was identified in three individuals from a four generation Greek family. The membrane potential in cells stably expressing hKir6.1 and hSUR2B with p.Gly814Trp was hyperpolarized compared to cells expressing WT channels, and inside-out patch-clamp assays of KATP channels formed with hSUR2B p.Gly814Trp demonstrated a decreased sensitivity to ATP inhibition, confirming a relatively mild GOF effect of this variant. The specific location of the variant reveals an unrecognized functional role of the first glycine in the signature motif of the nucleotide binding domains in ATP-binding cassette (ABC) protein ion channels.
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The significant inconsistency between the experimental and simulation results of the free energy for the translocon-assisted insertion of the transmembrane helix (TMH) has not been reasonably explained. Understanding the mechanism of TMH insertion through the translocon is the key to solving this problem. In this study, we performed a series of coarse-grained molecular dynamics simulations and calculated the potential mean forces (PMFs) for three insertion processes of a hydrophobic TMH. The simulations reveal the pathway of the TMH insertion assisted by a translocon. The results indicate that the TMH contacts the top of the lateral gate first and then inserts down the lateral gate, which agrees with the sliding model. The TMH begins to transfer laterally to the bilayer when it is blocked by the plug and reaches the exit of the lateral gate, where there is a free energy minimum point. We also found that the connecting section between TM2 and TM3 of Sec61α prevented TMH from leaving the lateral gate and directly transitioning to the surface-bound state. These findings provide insight into the mechanism of the insertion of TMH through the translocon.
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Simulação de Dinâmica Molecular , Canais de Translocação SEC , Canais de Translocação SEC/química , Canais de Translocação SEC/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/química , Proteínas de Membrana/química , Conformação Proteica em alfa-HéliceRESUMO
Fully understanding the anisotropic effect of silicon surface orientations in local anodic oxidation (LAO) nanolithography processes is critical to the precise control of oxide quality and rate. This study used ReaxFF MD simulations to reveal the surface anisotropic effects in the LAO through the analysis of adsorbed species, atomic charge, and oxide growth. Our results show that the LAO behaves differently on silicon (100), (110), and (111) surfaces. Specifically, the application of an electric field significantly increases the quantity of surface-adsorbed -OH2 while reducing -OH on the (111) surface, and results in a higher charge on a greater number of Si atoms on the (100) surface. Moreover, the quantity of surface-adsorbed -OH plays a pivotal role in influencing the oxidation rate, as it directly correlates with an increased formation rate of Si-O-Si bonds. During bias-induced oxidation, the (111) surface appears with a high initial oxidation rate among three surfaces, while the (110) surface underwent increased oxidation at higher electric field strengths. This conclusion is based on the analysis of the evolution of Si-O-Si bond number, surface elevation, and oxide thickness. Our findings align well with prior theoretical and experimental studies, providing deeper insights and clear guidance for the fabrication of high-performance nanoinsulator gates using LAO nanolithography.
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Hyperlipidemia is a common metabolic disorder that can lead to cardiovascular disease. PDK4 is a key enzyme that regulates glucose and fatty acid metabolism and homeostasis. The aim of this study is to explore the correlation between PDK4 expression and dyslipidemia in obese children, and to find new therapeutic targets for hyperlipidemia in children. The expression of PDK4 in serum was detected by qRT-PCR. Receiver operating characteristic curve was used to analyze the relationship between PDK4 and dyslipidemia. Upstream miRNAs of PDK4 were predicted by the database and verified by dual luciferase reporter gene assay and detected by qRT-PCR. The hyperlipidemia mouse model was established by high-fat diet (HFD) feeding, and the metabolic disorders of mice were detected. PDK4 is poorly expressed in the serum of obese children. The upstream of PDK4 may be inhibited by miR-107, miR-27a-3p, and miR-106b-5p, which are highly expressed in the serum of obese children. Overexpression of PDK4 improves lipid metabolism in HFD mice. miR-27a-3p silencing upregulates PDK4 to improve lipid metabolism. In conclusion, PDK4 has a diagnostic effect on dyslipidemia in children, while lipid metabolism in hyperlipidemic mice could be mitigated by upregulation of PDK4, which was inhibited by miR-107, miR-27a-3p and miR-106b-5p on upstream.
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Dislipidemias , Hiperlipidemias , MicroRNAs , Obesidade Infantil , Humanos , Criança , Camundongos , Animais , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Dislipidemias/genéticaRESUMO
A novel actinobacterium, strain HUAS 3T, was isolated from the rhizosphere soil of Cathaya argyrophylla collected in Hunan Province, PR China. Strain HUAS 3T contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The dominant menaquinones were MK-9(H4), MK-9(H6), MK-10(H2) and MK-9(H4). The polar lipids consisted of diphosphatidylglycerol, phospholipids, phosphatidylethanolamine, phosphatidylglycerol, phosphotidylinositol and phosphatidylinositol mannosides. The main cellular fatty acids (>5.0â%) were C17â:â1 ω8c, iso-C16â:â0, C18â:â1 ω9c, iso-C15â:â0, C16â:â0 and summed feature 3 (C16â:â1 ω6c and/or C16â:â1 ω7c). The DNA G+C content of the novel strain's genome sequence, consisting of 7â196â442 bp, was 72.8âmol%. The full-length 16S rRNA gene sequence analysis indicated that strain HUAS 3T belonged to the genus Micromonospora and showed highest similarities to Micromonospora fluminis A38T (99.44â%), Micromonospora echinospora DSM 43816T (99.23â%), Micromonospora tulbaghiae DSM 45142T (99.23â%), Micromonospora solifontis PPF5-17T (99.16â%) and Micromonospora endolithica DSM 44398T (98.96â%). Phylogenetic trees based on 16S rRNA gene sequences showed that strain HUAS 3T was closely related to M. fluminis A38T, M. tulbaghiae DSM 45142T and M. solifontis PPF5-17T. The phylogenomic tree revealed that strain HUAS 3T was closely related to Micromonospora pallida DSM 43817T. However, the average nucleotide identity (ANIb/ANIm) and the digital DNA-DNA hybridization values between them were 84.75â/88.16 and 30.80â%, respectively, far less than the 95-96 and 70â% cut-off points recommended for delineating species. Furthermore, strain HUAS 3T was distinct from the type strain of M. pallida in terms of phenotypic and chemotaxonomic characteristics. In summary, strain HUAS 3T represents a novel Micromonospora species, for which the name Micromonospora cathayae sp. nov. is proposed. The type strain is HUAS 3T (=MCCC 1K08599T=JCM 36275T).