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Dracaena cambodiana Pierre ex Gagn. (Asparagaceae) is the source plant of Dragon's blood and has high ornamental values in gardening. Currently, this species is classified as the second-class state-protected species in the National Key Protected Wild Plants (NKPWP) of China. However, limited genomic data has hindered a more comprehensive scientific understanding of the processes involved in the production of Dragon's blood and the related conservation genomics research. In this study, we assembled a haplotype-resolved genome of D. cambodiana. The haploid genomes, haplotype A and haplotype B, are 1,015.22 Mb and 1,003.13 Mb in size, respectively. The completeness of haplotype A and haplotype B genomes was 98.60% and 98.20%, respectively, using the "embryophyta_10" dataset. Haplotype A and haplotype B genomes contained 27,361 and 27,066 protein-coding genes, respectively, with nearly all being functionally annotated. These findings provide new insights into the genomic characteristics of D. cambodiana and will offer additional genomic resources for studying the biosynthesis mechanism of Dragon's blood and the horticultural application of Dragon trees.
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Dracaena , Genoma de Planta , Haplotipos , Dracaena/genética , China , Cromosomas de las Plantas/genética , Extractos VegetalesRESUMEN
This study aimed to reveal the impact of bacterial dynamics on the quality and biogenic amine (BA) accumulation of dry-cured Chinese bacon (Larou). Physicochemical parameters, free amino acids, BAs, amino acid decarboxylase, and microbial profiles were determined, and their relationships were explored during Larou ripening and storage. The results showed that moisture and sodium nitrite decreased significantly during the Larou ripening stage (p < 0.05), while pH, NaCl, TBARS, and total volatile basic nitrogen considerably increased (p < 0.05). BAs were mainly formed during the stages of dry-ripening and storage of Larou and may present a risk of tyramine and phenylethylamine poisoning. Firmicutes and Actinobacteriota were the predominant phyla, and the dominant genera were Staphylococcus, Corynebacterium and Lactococcus. Correlation analysis showed Corynebacterium, Brevibacterium, Lactobacillus, Tetragenococcus and Staphylococci spp. played a crucial role in determining the quality and safety of Larou. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01472-1.
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The rapid development of radar detection systems has led to an increased sensitivity to the electromagnetic (EM) scattering properties of detected targets. Flexible and adaptable EM scattering properties significantly enhance the survivability of battlefield weapons. This paper presents the design of a novel multifunctional metamaterial with reconfigurable EM scattering properties based on a bistable curved beam. In addition to the cushioning and energy absorption properties of curved beams, the metamaterial achieves more than 90% EM absorption in the frequency range of 2.17-17.31 GHz, with a relative thickness of only 0.09λL. The bistable nature of the metamaterial allows it to switch between different states. Moreover, combined with the digital coding, this metamaterial can continuously adjust the absorbing bandwidth and further enhance the EM absorption rate within a specific frequency band range. If applied to satellite configurations, the developed metamaterial significantly reduces the radar cross section and offers potential applications in reconfiguring EM scattering properties, when applied to satellite configurations. By actively controller and reconstructing the EM scattering properties at certain frequency points, the metamaterial can achieve camouflage, providing innovative solutions for future stealth technology, electronic countermeasures, and deception jamming in radar detection.
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Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.
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T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it's involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.
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Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM2.5 and PM10) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM2.5 and PM10) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 µg/m3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM2.5); HR: 1.13, 95%CI: 1.11, 1.15 (PM10)). The presence of diabetes and dyslipidemia increased the risk of PM10-induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke.
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In our previous studies, 3-O-ß-D-galactosylated resveratrol (Gal-Res) was synthesized by structural modification and then 3-O-ß-D-galactosylated resveratrol polydopamine nanoparticles (Gal-Res NPs) were successfully prepared to improve the bioavailability and liver distribution of Res. However, the pharmacodynamic efficacy and specific mechanism of Gal-Res NPs on hepatocellular carcinoma remain unclear. Herein, liver cancer model mice were successfully constructed by xenograft tumor modeling. Gal-Res NPs (34.2â¯mg/kg) significantly inhibited tumor growth of the liver cancer model mice with no significant effect on their body weight and no obvious toxic effect on major organs. Additionally, in vitro cellular uptake assay showed that Gal-Res NPs (37.5⯵mol/L) increased the uptake of Gal-Res by Hepatocellular carcinoma (HepG2) cells, and significantly inhibited the cell migration and invasion. The experimental results of Hoechst 33342/propyl iodide (PI) double staining and flow cytometry both revealed that Gal-Res NPs could remarkably promote cell apoptosis. Moreover, the Western blot results revealed that Gal-Res NPs significantly regulated the Bcl-2/Bax and AKT/GSK3ß/ß-catenin signaling pathways. Taken together, the in vitro/in vivo results demonstrated that Gal-Res NPs significantly improved the antitumor efficiency of Gal-Res, which is a potential antitumor drug delivery system.
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BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.
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Densidad Ósea , Estudio de Asociación del Genoma Completo , Degeneración del Disco Intervertebral , Análisis de la Aleatorización Mendeliana , Humanos , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/epidemiología , Factores de Riesgo , Masculino , Femenino , Análisis MultivarianteRESUMEN
Silicon, renowned for its remarkable energy density, has emerged as a focal point in the pursuit of high-energy storage solutions for the next generation. Nevertheless, silicon electrodes are known to undergo significant volume expansion during the insertion of lithium ions, leading to structural deformation and the development of internal stresses, and causing a rapid decline in battery capacity and overall lifespan. To gain deeper insights into the intricacies of charge rate effects, this study employs a combination of in situ measurements and computational modeling to elucidate the cyclic performance of composite silicon electrodes. The findings derived from the established model and curvature measurement system unveil the substantial alterations in stress and deformation as a consequence of varying charge rates. Notably, the active layer experiences compressive forces that diminish as the charge rate decreases. At a charge rate of 0.2, the active layer endures a maximum stress of 89.145 MPa, providing a comprehensive explanation for the observed deterioration in cycling performance at higher charge rates. This study not only establishes a fundamental basis for subsequent stress analyses of silicon electrodes but also lays a solid foundation for further exploration of the impact of charge rates on composite silicon electrodes.
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The mechanical response is one of the main factors that influence the capacity and number of cycles of lithium batteries, which hinder its wide application. Therefore, it is crucial to perform an in-depth investigation of the electro-chemo-mechanical coupling performance and work mechanism of battery electrodes during the electrochemical reaction process. Usually, graphite is the main active material used in commercially used batteries, while silicon is gaining worldwide attention because of its large energy density. Here, graphite and silicon composite electrodes were prepared to obtain the electro-chemo-mechanical response during electrochemical cycling by an in situ bending deformation measurement. The findings indicate that the composite electrodes could induce a large bending deformation, with an increase in the state of charge (C-rate). And, with an increase in the C-rate, the deformation degree of the silicon composite electrode increases, while that of the graphite composite electrode decreases due to the hardening properties of the graphite particles. In addition, increasing the thickness ratio could induce an increase in the peak stress for both composite electrodes. This work gives a detailed analysis of the mechanical properties of composite electrodes and finds the working mechanism of the C-rate and thickness ratio, which can supply suggestions for the development of high-performance batteries.
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Background: Emerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of <26.5 µmol/L within 48 h after invasive mechanical ventilation (MV) on the short-term mortality of critically ill patients in the geriatric population. Methods: We conducted a retrospective, observational, multicenter cohort study enrolling consecutive elderly patients (≥75 years) who received invasive MV from January 2008 to December 2020. Recursive partitioning was used to calculate the ratio of SCr rise from baseline within 48 h after MV and divided into six groups, (1) <10%, (2) 10%-<20%, (3) 20%-<30%, (4) 30%-<40%, (5) 40%-<50%, and (6) ≥50%, where the reference interval was defined as the ratio <10% based on an analysis, which confirmed that the lowest mortality risk was found in this range. Clinical data and laboratory data were noted. Their general conditions and clinical characteristics were compared between the six groups. Prognostic survival factors were identified using Cox regression analysis. Kaplan-Meier survival analysis was employed for the accumulative survival rate. Results: A total of 1292 patients (1171 men) with a median age of 89 (interquartile range: 85-92) with MV were suitable for further analysis. In all, 376 patients had any stage of early AKI, and 916 patients had no AKI. Among 916 non-AKI patients, 349 patients were in the ratio <10%, 291 in the 10%-<20% group, 169 in the 20%-<30% group, 68 in the 30%-<40% group, 25 in the 40%-<50% group, and 14 in the ≥50% group. The 28-day mortality rates in the six groups from the lowest (<10%) to the highest (≥50%) were 8.0%, 16.8%, 28.4%, 54.4%, 80.0%, and 85.7%, respectively. In the multivariable-adjusted analysis, patients with a ratio of 10%-<20% (hazard ratio [HR]=2.244; 95% confidence interval [CI]: 1.410 to 3.572; P=0.001), 20%-<30% (HR=3.822; 95% CI: 2.433 to 6.194; P <0.001), 30%-<40% (HR=10.472; 95% CI: 6.379 to 17.190; P <0.001), 40%-<50% (HR=13.887; 95% CI: 7.624 to 25.292; P <0.001), and ≥50% (HR=13.618; 95% CI: 6.832 to 27.144; P <0.001) had relatively higher 28-day mortality rates. The 90-day mortality rates in the six strata were 30.1%, 35.1%, 45.0%, 60.3%, 80.0%, and 85.7%, respectively. Significant interactions were also observed between the ratio and 90-day mortality: patients with a ratio of 10%-<20% (HR=1.322; 95% CI: 1.006 to 1.738; P=0.045), 20%-<30% (HR=1.823; 95% CI: 1.356 to 2.452; P <0.001), 30%-<40% (HR=3.751; 95% CI: 2.601 to 5.410; P <0.001), 40%-<50% (HR=5.735; 95% CI: 3.447 to 9.541; P <0.001), and ≥50% (HR=6.305; 95% CI: 3.430 to 11.588; P <0.001) had relatively higher 90-day mortality rates. Conclusions: Our study suggests that a ≥ 10% SCr rise from baseline within 48 h after MV was independently associated with short-term all-cause mortality in mechanically ventilated elderly patients.
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Spinel cathode materials have great application prospects in lithium batteries (LIBs) due to their characteristics of abundant raw materials, simple preparation processes, and cobalt-free nature. During the electrochemical cycles, the specific capacity of the electrodes decreases significantly due to the dissolution of excess metal ions and mechanical degradation, which hinder their further application and development. Here, a bending curvature measurement system (BCMS) was designed to simultaneously measure the mechanical properties of the spinel cathodes during the electrochemical reaction. Three types of cathodes were chosen as the working cathode, and the coupled mechanical and electrochemical properties were analyzed to understand their degradation mechanism. During cycling, a hysteresis loop is observed for the curvature, modulus, plain strain, and stress, where LiMn2O4 (LMO) has the largest loop for the mechanical response while the LiNi0.5Mn1.5O4@Al2O3 (LNMO@Al) one has the smallest loop. Besides, the changing trend of LNMO@Al is the smallest in multiple cycles and it shows the more stable mechanical properties. This study shows from in situ mechanical measurements that the mechanical properties can greatly affect the electrochemical performance of the cathodes. These findings could offer new insights into the understanding of the electrochemical performance degradation in the spinel cathodes and can help develop strategies to enhance the performance of LIBs.
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BACKGROUND: Telomere shortening is strongly associated with cardiovascular aging and disease, and patients with shorter telomeres in peripheral blood leukocytes are at higher risk of cardiovascular diseases such as heart failure and atrial fibrillation (AF). Telomerase reverse transcriptase (TERT) maintains telomere length, and overexpression of TERT has been shown to reduce cardiomyocyte apoptosis and myocardial infarct size, and extend the lifespan of aged mice. However, the specific impact of TERT on the electrophysiology of cardiomyocytes remains to be elucidated. The aims of this study were to evaluate the role of TERT in Ca2+ homeostasis and mitochondrial function in atrial myocytes as well as the underlying mechanisms. METHODS: TERT overexpressed and silenced HL-1 cells were constructed with lentiviruses, and the respective empty lentiviral vectors were used as negative controls. Then the patch clamp technique was used to record the electrophysiological characteristics such as cell action potential duration (APD) and L-type Ca2+ currents (ICa,L), flow cytometry was used to detect intracellular Ca2+ concentration and mitochondrial membrane potential (MMP), and the Seahorse assay was used to measure the oxygen consumption rate (OCR). RESULTS: TERT silencing led to intracellular Ca2+ overload, shortened APD, decreased ICa,L current density, altered Ca2+ gating mechanism, decreased MMP and OCR, and increased reactive oxygen species (ROS), whereas TERT overexpression led to the reverse effects. Additionally, TERT silencing resulted in intracellular Ca2+ overload with decreased expression of the SERCA2a, CaV1.2, and NCX1.1, whereas TERT overexpression had opposing effects. Furthermore, we discovered that TERT could regulate the expression of p53 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The expression of PGC-1α was downregulated by the p53 agonist Tenovin-6 but upregulated by the p53 inhibitor PFTα. The effects of the PGC-1α inhibitor SR-18292 on intracellular Ca2+ and cell electrophysiology were similar to those of silencing TERT, whereas the PGC-1α agonist ZLN005 produced comparable outcomes to TERT overexpression. CONCLUSIONS: TERT silencing-induced Ca2+ overload and mitochondrial dysfunction may be one mechanism of age-related AF. Overexpression of TERT reduced the basis for arrhythmia formation such as AF, suggesting a favorable safety profile for TERT therapy. TERT regulated intracellular Ca2+ homeostasis and mitochondrial function through the p53/PGC-1α pathway. In addition, PGC-1α might be a novel target for AF, suggesting that intervention for AF should be not limited to abnormal cation handling.
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Calcio , Homeostasis , Potencial de la Membrana Mitocondrial , Miocitos Cardíacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Telomerasa , Proteína p53 Supresora de Tumor , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Animales , Calcio/metabolismo , Ratones , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Telomerasa/metabolismo , Telomerasa/genética , Miocitos Cardíacos/metabolismo , Línea Celular , Mitocondrias/metabolismo , Potenciales de Acción , Transducción de SeñalRESUMEN
Prevalent interactions among marine phytoplankton triggered by long-range climatic stressors are well-known environmental disturbers of community structure. Dynamic response of phytoplankton physiology is likely to come from interspecies interactions rather than direct climatic effect on single species. However, studies on enigmatic interactions among interspecies, which are induced by bioactive extracellular compounds (BECs), especially between related harmful algae sharing similar shellfish toxins, are scarce. Here, we investigated how BECs provoke the interactions between two notorious algae, Alexandrium minutum and Gymnodinium catenatum, which have similar paralytic shellfish toxin (PST) profiles. Using techniques including electron microscopy and transcriptome analysis, marked disruptions in G. catenatum intracellular microenvironment were observed under BECs pressure, encompassing thylakoid membrane deformations, pyrenoid matrix shrinkage and starch sheaths disappearance. In addition, the upregulation of gene clusters responsible for photosystem-I Lhca1/4 and Rubisco were determined, leading to weaken photon captures and CO2 assimilation. The redistribution of lipids and proteins occurred at the subcellular level based on in situ focal plane array FTIR imaging approved the damages. Our findings illuminated an intense but underestimated interspecies interaction triggered by BECs, which is responsible for dysregulating photosynthesis and organelle function in inferior algae and may potentially account for fitness alteration in phytoplankton community.
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Kiwifruit ripening is a complex and highly coordinated process that occurs in conjunction with the formation of fruit edible quality. The significance of epigenetic changes, particularly the impact of N6-methyladenosine (m6A) RNA modification on fruit ripening and quality formation, has been largely overlooked. We monitored m6A levels and gene expression changes in kiwifruit at four different stages using LC-MS/MS, MeRIP, RNA-seq, and validated the function of AcALKBH10 through heterologous transgenic expression in tomato. Notable m6A modifications occurred predominantly at the stop codons and the 3' UTRs and exhibited a gradual reduction in m6A levels during the fruit ripening process. Moreover, these m6A modifications in the aforementioned sites demonstrated a discernible inverse relationship with the levels of mRNA abundance throughout the ripening process, suggesting a repression effect of m6A modification in the modulation of kiwifruit ripening. We further demonstrated that AcALKBH10 rather than AcECT9 predominantly regulates m6A levels in ripening-related genes, thereby exerting the regulatory control over the ripening process and the accumulation of soluble sugars and organic acids, ultimately influencing fruit ripening and quality formation. In conclusion, our findings illuminate the epi-regulatory mechanism involving m6A in kiwifruit ripening, offering a fresh perspective for cultivating high-quality kiwifruit with enhanced nutritional attributes.
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SGT1 is a highly conserved eukaryotic protein that plays a vital role in the growth, development, and immunity in both animals and plants. Although some SGT1 interactors have been identified, the molecular regulatory network of SGT1 remains unclear. SGT1 serves as a co-chaperone to stabilize protein complexes such as the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors, thereby positively regulating plant immunity. SGT1 has also been found to be associated with the SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. However, whether SGT1 targets immune repressors to coordinate plant immune activation remains elusive. Here, we constructed a toolbox for TurboID- and split-TurboID-based proximity labeling (PL) assays in Nicotiana benthamiana. We used the PL toolbox to explore the SGT1 interactome during pre- and post-immune activation. The comprehensive SGT1 interactome network that we identified highlights a dynamic shift from proteins associated with plant development to those linked with plant immune responses. SGT1 interacts with Necrotic Spotted Lesion 1 (NSL1) that negatively regulates salicylic acid (SA)-mediated defense by interfering with the nucleocytoplasmic trafficking of Non-expressor of Pathogenesis-Related Genes 1 (NPR1) during N NLR-mediated response to tobacco mosaic virus (TMV). SGT1 promotes the SCF-dependent degradation of NSL1 to facilitate immune activation, while salicylate-induced protein kinase (SIPK)-mediated phosphorylation of SGT1 further potentiates this process. Besides N NLR, NSL1 also functions in several other NLR-mediated immunity. Our study unveils the regulatory landscape of SGT1 and reveals a novel SGT1-NSL1 signaling module that orchestrates plant innate immunity.
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Freshwater discharge from ice sheets induces surface atmospheric cooling and subsurface ocean warming, which are associated with negative and positive feedbacks respectively. However, uncertainties persist regarding these feedbacks' relative strength and combined effect. Here we assess associated feedbacks in a coupled ice sheet-climate model, and show that for the Antarctic Ice Sheet the positive feedback dominates in moderate future warming scenarios and in the early stage of ice sheet retreat, but is overwhelmed by the negative feedback in intensive warming scenarios when the West Antarctic Ice Sheet undergoes catastrophic collapse. The Atlantic Meridional Overturning Circulation is affected by freshwater discharge from both the Greenland and the Antarctic ice sheets and, as an interhemispheric teleconnection bridge, exacerbates the opposing ice sheet's retreat via the Bipolar Seesaw. These results highlight the crucial role of ice sheet-climate interactions via freshwater flux in future ice sheet retreat and associated sea-level rise.
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AIMS: Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressing neurodegenerative disease caused by CSF1R gene mutations. This study aimed to identify and investigate the effect of a novel intronic mutation (c.1754-3C>G) of CSF1R on splicing. METHODS: A novel intronic mutation was identified using whole-exome sequencing. To investigate the impact of this mutation, we employed various bioinformatics tools to analyze the transcription of the CSF1R gene and the three-dimensional structure of its encoded protein. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the findings. RESULTS: A novel mutation (c.1754-3C>G) in CSF1R was identified, which results in exon 13 skipping due to the disruption of the 3' splice site consensus sequence NYAG/G. This exon skipping event was further validated in the peripheral blood of the mutation carrier through RT-PCR and Sanger sequencing. Protein structure prediction indicated a disruption in the tyrosine kinase domain, with the truncated protein showing significant structural alterations. CONCLUSIONS: Our findings underscore the importance of intronic mis-splicing mutations in the diagnosis and management of CSF1R-related leukoencephalopathy.
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Intrones , Leucoencefalopatías , Mutación , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Leucoencefalopatías/genética , Mutación/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Intrones/genética , Femenino , Masculino , Adulto , Empalme del ARN/genética , Receptor de Factor Estimulante de Colonias de MacrófagosRESUMEN
The majority of rod-shaped and some filamentous plant viruses encode a cysteine-rich protein (CRP) that functions in viral virulence; however, the roles of these CRPs in viral infection remain largely unknown. Here, we used barley stripe mosaic virus (BSMV) as a model to investigate the essential role of its CRP in virus morphogenesis. The CRP protein γb directly interacts with BSMV coat protein (CP), the mutations either on the His-85 site in γb predicted to generate a potential CCCH motif or on the His-13 site in CP exposed to the surface of the virions abolish the zinc-binding activity and their interaction. Immunogold-labeling assays show that γb binds to the surface of rod-shaped BSMV virions in a Zn2+-dependent manner, which enhances the RNA binding activity of CP and facilitates virion assembly and stability, suggesting that the Zn2+-dependent physical association of γb with the virion is crucial for BSMV morphogenesis. Intriguingly, the tightly binding of diverse CRPs to their rod-shaped virions is a general feature employed by the members in the families Virgaviridae (excluding the genus Tobamovirus) and Benyviridae. Together, these results reveal a hitherto unknown role of CRPs in the assembly and stability of virus particles, and expand our understanding of the molecular mechanism underlying virus morphogenesis.
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Virión , Zinc , Zinc/metabolismo , Virión/metabolismo , Proteínas de la Cápside/metabolismo , Ensamble de Virus/fisiología , Virus de Plantas/metabolismo , Virus de Plantas/fisiología , Enfermedades de las Plantas/virología , Cisteína/metabolismo , Proteínas Virales/metabolismo , MorfogénesisRESUMEN
The combination of CRISPR/Cas12a and functional DNA provides the possibility of constructing biosensors for detecting non-nucleic-acid targets. In the current study, the duplex protospacer adjacent motif (PAM) in the activator of CRISPR/Cas12a was used as a molecular switch, and a sensitive adenosine triphosphate (ATP) detection biosensor was constructed using an allosteric probe-conjugated PAM site formation in hybridization chain reaction (HCR) integrated with the CRISPR/Cas12a system (APF-CRISPR). In the absence of ATP, an aptamer-containing probe (AP) is in a stem-loop structure, which blocks the initiation of HCR. In the presence of ATP, the structure of AP is changed upon ATP binding, resulting in the release of the HCR trigger strand and the production of long duplex DNA with many PAM sites. Since the presence of a duplex PAM site is crucial for triggering the cleavage activity of CRISPR/Cas12a, the ATP-dependent formation of the PAM site in HCR products can initiate the FQ-reporter cleavage, allowing ATP quantification by measuring the fluorescent signals. By optimizing the sequence elements and detection conditions, the aptasensor demonstrated superior detection performance. The limit of detection (LOD) of the assay was estimated to be 1.16 nM, where the standard deviation of the blank was calculated based on six repeated measurements. The dynamic range of the detection was 25-750 nM, and the whole workflow of the assay was approximately 60 min. In addition, the reliability and practicability of the aptasensor were validated by comparing it with a commercially available chemiluminescence kit for ATP detection in serum. Due to its high sensitivity, specificity, and reliable performance, the APF-CRISPR holds great potential in bioanalytical studies for ATP detection. In addition, we have provided a proof-of-principle for constructing a CRISPR/Cas12a-based aptasensor, in which the PAM is utilized to regulate Cas12a cleavage activity.