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Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate-mutagenized rice mutant library, we isolated the PEG tolerance mutant 97-1 (ptm97-1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought-resistant phenotype of ptm97-1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6-GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild-type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance.
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The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.
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BACKGROUND: Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. METHODS: Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl-biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. RESULTS: We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. CONCLUSIONS: Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.
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Neoplasias da Mama , Proliferação de Células , Claudinas , Lipoilação , Proteína de Ligação a Elemento Regulador de Esterol 1 , Humanos , Animais , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Camundongos , Claudinas/metabolismo , Claudinas/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Metástase Neoplásica , Proteínas ras/metabolismo , Proteínas ras/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundárioRESUMO
Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.
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Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Preclinical studies indicate that these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway, such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to the inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the combination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma.
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OBJECTIVE: To determine a risk scoring system for predicting advanced colorectal neoplasia (ACN) within subcentimetric polyps in a large Asian population. METHODS: A retrospective study was conducted in Hong Kong SAR, China involving participants who underwent colonoscopy between 2008 and 2015. A random sample of 20 072 subjects were included as the derivation cohort to assess ACN-associated independent factors using logistic regression modeling. Another 8603 subjects formed a validation cohort. A risk scoring system was developed and its performance was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: The risk scores were assigned based on the following criteria: (a) patients who were admitted from inpatient colonoscopy (2.2) or not (1); (b) with three or more chronic diseases (hypertension, diabetes mellitus, hyperlipidemia, heart disease, or cancer) (1.7) or not (1); (c) anemia (1.3) or without anemia (1); (d) receiving aspirin (0.5) or not (1); (e) receiving other nonsteroidal anti-inflammatory drugs (0.3) or not (1); (f) male (1.2) or female gender (1); (g) age <55 (1), 55-64 (1.4), 65-69 (2), 70 years or above (2.2). ACN was more common in those with scores of 2.192 or higher, and they were classified as high risk (HR). The prevalence of ACN in the validation cohort was 13.28% and 3.56% in the HR and low-risk groups, respectively. In both the derivation and validation cohorts, AUROC of the risk-scoring model was 0.7138. CONCLUSION: Physicians are recommended to utilize this validated score for risk-stratification of patients having subcentimetric polyps.
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Lakes and wetlands play pivotal roles in global organic matter storage, receiving significant inputs of organic material. However, the co-metabolic processes governing the decomposition of these organic materials and their impact on greenhouse gas emissions remain inadequately understood. This study aims to assess the effects of mixed decomposition involving macrophytes and cyanobacteria on carbon emissions. A series of microcosms was established to investigate the decomposition of macrophyte residues and algae over a period of 216 days. A two-component kinetic model was utilized to estimate methane (CH4) production rates. Gas isotope technology was employed to discern the contributions of CH4 produced by macrophyte residues or algae. Quantitative PCR and analysis of 16S rRNA gene amplicons were employed to assess changes in functional genes and microbial communities. There were significant differences in the cumulative carbon release from the decomposition of different plant types due to the addition of carbon sources. After adding algae, the cumulative emission of CH4 increased significantly. The δ13C-CH4 partitioning indicated that CH4 originated exclusively from the fresh organic carbon of macrophyte residues, while it shifted to algae source after adding algae. The synergistic effect of the mixed decomposition on the CH4 emissions was greater than the sum of the individual decompositions. The microbial community richness was higher in the single plant residue treatment compared to the mixed treatment with algae addition, while microbial evenness in the sediment increased steadily in each treatment. Our findings emphasize the pronounced co-metabolic effect observed during the mixed decomposition of macrophytes and cyanobacteria.
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Eutrofização , Sedimentos Geológicos , Metano , Metano/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Cianobactérias/metabolismo , Cianobactérias/genética , Plantas/metabolismo , Microbiota , Água Doce/química , Água Doce/microbiologiaRESUMO
Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its effect on grain chalkiness, but the underlying molecular mechanisms remain to be clarified. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only increases grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms that orchestrate grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, highlighting the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings reveal potential targets for simultaneous enhancement of rice yield and quality.
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BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.
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Cárie Dentária , Placa Dentária , Humanos , Placa Dentária/microbiologia , Cárie Dentária/microbiologia , Cárie Dentária/terapia , Pré-Escolar , Masculino , Feminino , Microbiota , Anestesia Geral , RNA Ribossômico 16SRESUMO
To explore the compensation effect of aeration on tomato vegetative and reproductive growth in arid and semi-arid areas, a two-year field experiment was conducted with four micro-nano aeration ratios (0%, 5%, 10%, and 15%) and three nitrogen topdressing levels (80, 60, and 40 kg·ha-1) during the tomato growth period in Ningxia, China. The results showed that increasing the aeration ratio in the range of 0-15% was conducive to the enhancement of tomato root vigor (the ability of triphenyltetrazolium chloride to be reduced, 3-104%) and the leaf net photosynthetic rate (14-63%), favorable to the facilitation of plant dry matter accumulation (3-59%) and plant nitrogen accumulation (2-70%), and beneficial to the improvement of tomato yield (12-44%) and fruit quality. Interestingly, since the aeration ratio exceeded 10%, the increase in the aeration ratio showed no significant effects on the single-fruit weight, tomato yield, and fruit quality. Moreover, with aerated underground drip irrigation, properly reducing the traditional nitrogen topdressing level (80 kg·ha-1) by 25% was favorable for enhancing tomato root vigor (5-31%), increasing tomato yield (0.5-9%), and improving fruit soluble solid accumulation (2-5%) and soluble sugar formation (4-9%). Importantly, increasing the aeration ratio by 5% could compensate for the adverse effects of reducing the nitrogen topdressing level by 25% by improving the leaf photosynthetic rate, promoting plant dry matter accumulation, increasing tomato yield, and enhancing the soluble solid and soluble sugar accumulation in tomato fruits. Synthetically considering the decrease in the nitrogen topdressing amount, leading to plant growth promotion, a tomato yield increase, and fruit quality improvement, a favorable nitrogen topdressing level of 60 kg·ha-1 and the corresponding proper aeration ratio of 10% were suggested for tomato underground drip irrigation in the Yinbei Irrigation District of Ningxia.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.
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Anti-Inflamatórios , Chromolaena , Edema , Etanol , Hemostáticos , Extratos Vegetais , Cicatrização , Animais , Coelhos , Cicatrização/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Camundongos , Masculino , Hemostáticos/farmacologia , Etanol/química , Chromolaena/química , Edema/tratamento farmacológico , Edema/induzido quimicamente , Ratos , Pele/efeitos dos fármacos , Feminino , Anti-Infecciosos/farmacologia , Anti-Infecciosos/isolamento & purificação , Folhas de Planta/química , Hipersensibilidade/tratamento farmacológico , Xilenos , Caules de Planta/químicaRESUMO
Improving the kinetics and selectivity of CO2/CO electroreduction to valuable multi-carbon products is a challenge for science and is a requirement for practical relevance. Here we develop a thiol-modified surface ligand strategy that promotes electrochemical CO-to-acetate. We explore a picture wherein nucleophilic interaction between the lone pairs of sulfur and the empty orbitals of reaction intermediates contributes to making the acetate pathway more energetically accessible. Density functional theory calculations and Raman spectroscopy suggest a mechanism where the nucleophilic interaction increases the sp2 hybridization of CO(ad), facilitating the rate-determining step, CO* to (CHO)*. We find that the ligands stabilize the (HOOC-CH2)* intermediate, a key intermediate in the acetate pathway. In-situ Raman spectroscopy shows shifts in C-O, Cu-C, and C-S vibrational frequencies that agree with a picture of surface ligand-intermediate interactions. A Faradaic efficiency of 70% is obtained on optimized thiol-capped Cu catalysts, with onset potentials 100 mV lower than in the case of reference Cu catalysts.
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Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker's yeast Saccharomyces cerevisiae, the X- and Y'-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y'-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y'-elements) in telomere maintenance. Deletion of Y'-elements (SY12YΔ), X-elements (SY12XYΔ+Y), or both X- and Y'-elements (SY12XYΔ) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12YΔ, SY12XYΔ+Y, and SY12XYΔ cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X- and Y'-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.
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Sequências Repetitivas de Ácido Nucleico , Saccharomyces cerevisiae , Telomerase , Telômero , Saccharomyces cerevisiae/genética , Telômero/metabolismo , Telômero/genética , Sequências Repetitivas de Ácido Nucleico/genética , Telomerase/genética , Telomerase/metabolismo , Homeostase do Telômero , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Deleção de SequênciaRESUMO
Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress, with reactive oxygen species (ROS) emerging as pivotal systemic signals in plant stress responses. However, the exact role of ROS as root-to-shoot signals in the drought response has not been determined. In this study, we reveal that compared with wild-type plants, ferric reductase defective 3 (frd3) mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) transcript levels and abscisic acid (ABA) contents in leaves as well as increased hydrogen peroxide (H2O2) levels in roots and leaves. Grafting experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype, indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in leaves. Intriguingly, the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion, suggesting that H2O2 may be involved in long-distance signaling. Moreover, the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 mutant. Taken together, our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance, providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Secas , Regulação da Expressão Gênica de Plantas , Raízes de Plantas , Transdução de Sinais , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Transdução de Sinais/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Peróxido de Hidrogênio/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Mutação , Estresse Fisiológico/genética , Espécies Reativas de Oxigênio/metabolismo , Resistência à Seca , Proteínas de PlantasRESUMO
PURPOSE: Patients with gynaecological cancer often experience psychological issues due to multiple stressors. Psychological disturbances have debilitating effects on patients with gynaecological cancer. In recent decades, digital psychosocial interventions have rapidly advanced and been incorporated into mental health interventions. Digital psychosocial interventions could provide patients with several benefits over traditional in-person interventions, including convenience, anonymity, flexible scheduling, and geographic mobility. The aim of this systematic review was to synthesize the effectiveness of digital psychosocial intervention in reducing psychological distress, depression, and anxiety and improving health-related quality of life in patients with gynaecological cancer. METHODS: Three-step extensive search was performed on 22 December 2022 from nine bibliographic databases, trial registries and grey literature. Experimental studies involving patients with gynaecological cancer utilizing digital psychosocial interventions for the improvement of mental health outcomes were included. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was analysed by Cochran's Q test and I2. Subgroup analyses were attempted to evaluate relative effect sizes of subgroup features. RESULTS: Meta-analysis of nine studies revealed small effect size in reduction of depression post-intervention (d = 0.24, 95% CI - 0.46 to - 0.02) and medium effect size in reduction of psychological distress post-intervention (d = 0.51, 95% CI - 0.81 to - 0.21) and follow-up (d = 0.65, 95% CI - 1.25 to - 0.05) compared to the control group. The effects of digital psychosocial interventions on anxiety and health-related quality of life were not statistically significant. CONCLUSIONS: Digital psychosocial interventions probably reduced psychological distress and slightly reduced depression amongst patients with gynaecological cancer compared to the control group, which can be integrated into clinical practice. Additional trials with rigorous methodology and bigger sample sizes are needed to validate findings. TRIAL REGISTRATION: PROSPERO (CRD42023389502).
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Ansiedade , Depressão , Neoplasias dos Genitais Femininos , Angústia Psicológica , Intervenção Psicossocial , Qualidade de Vida , Humanos , Feminino , Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/terapia , Ansiedade/etiologia , Ansiedade/terapia , Ansiedade/psicologia , Depressão/etiologia , Depressão/terapia , Depressão/psicologia , Intervenção Psicossocial/métodos , Estresse Psicológico/terapia , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Estresse Psicológico/prevenção & controleRESUMO
BACKGROUND: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk. METHODS: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors. RESULTS: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 µmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77). CONCLUSIONS: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.
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Demência , Dislipidemias , Hiperglicemia , Hipertensão , Síndrome Metabólica , Humanos , Ácido Úrico , Estudos Prospectivos , Fatores de Risco , Hipertensão/complicações , HDL-Colesterol , Triglicerídeos , Dislipidemias/complicações , Demência/etiologia , Demência/complicaçõesRESUMO
M2 macrophages are associated with the prognosis of bladder cancer. CLDN6 has been linked to immune infiltration and is crucial for predicting the prognosis in multi-tumor. The effect of CLDN6 on M2 macrophages in bladder cancer remains elusive. Here, we compared a total of 40 machine learning algorithms, then selected optimal algorithm to develop M2 macrophages-related signature (MMRS) based on the identified M2 macrophages related module. MMRS predicted the prognosis better than other models and associated to immunotherapy response. CLDN6, as an important variable in MMRS, was an independent factor for poor prognosis. We found that CLDN6 was highly expressed and affected immune infiltration, immunotherapy response, and M2 macrophages polarization. Meanwhile, CLDN6 promoted the growth of bladder cancer and enhanced the carcinogenic effect by inducing polarization of M2 macrophages. In total, CLDN6 is an independent risk factor in MMRS to predict the prognosis of bladder cancer.
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Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC50 values from 0.19 ± 0.08 to 1.03 ± 0.25 µM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75.
Assuntos
Glicosídeos Cardíacos , Moraceae , Glicosídeos Cardíacos/farmacologia , Glicosídeos Cardíacos/química , Extratos Vegetais/química , Moraceae/química , Antivirais/química , Glicosídeos/farmacologiaRESUMO
BACKGROUND: Maintaining ideal cardiovascular health scores (CHS) may indirectly contribute to reducing the risk of perioperative acute kidney injury (AKI), which has never been explored previously. In this study, we aimed to explore the relationship between CHS and AKI and provide new ideas for AKI prevention and treatment. METHODS: We examined the effects of CHS on the occurrence of AKI among 2783 participants from the Kailuan study, who received general anesthesia during noncardiac surgery from 2016 to 2020. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for AKI were calculated by using the logistic regression. RESULTS: Among 2783 participants 187 were diagnosed with perioperative AKI. We found an inverse relationship between the CHS scores and the risk of AKI. Participants with CHS score ≥ 10 had 57% decreased risk of AKI (OR = 0.43, 95% CI = 0.23, 0.79), compared with participants with CHS score ≤ 7, especially in men (OR = 0.39, 95% CI: 0.20, 0.76). In addition, participants who never smoked, exercised frequently, and had normal blood pressure had decreased risk of AKI, with corresponding ORs (95% CIs) of 0.66 (0.47, 0.91), 0.73 (0.60, 0.92), and 0.46 (0.28, 0.75), respectively. CONCLUSIONS: CHS was strongly associated with the risk of perioperative AKI, and higher CHS scores were associated with a lower risk of AKI. Further research is needed to explore the long-term effects of achieving and maintaining an ideal CHS on AKI risk.