RESUMEN
Here, a separation-free and label-free portable aptasensor is developed for rapid and sensitive analysis of tumor-derived exosomes (TEXs). It integrated a parallel rolling circle amplification (RCA) reaction, selective binding of metal ions or small molecules to nucleic acid-specific conformations, and a low-cost, highly sensitive handheld fluorometer. Lung cancer, for example, is targeted with two typical biomarkers (mucin 1 and programmed cell death ligand 1 (PD-L1)) on its exosomes. The affinity of aptamers to the targets modulated the amount of RCA products (T-Hg2+-T and cytosine (C)-rich single-stranded DNA), which in turn affected the fluorescence intensity of quantum dots (QDs) and methylene blue (MB). The results revealed that the limit of detection (LOD) of the handheld fluorometer for cell-derived exosomes can be as low as 30 particles mL-1. Moreover, its specificity, sensitivity, and area under the curve (AUC) are 93% (14/15), 92% (23/25), and 0.956, as determined by the analysis of 40 clinical samples. Retesting 16 of these samples with the handheld fluorometer yielded strong concordance between the fluorometer results and those acquired from clinical computed tomography (CT) and pathology.
Asunto(s)
Exosomas , Neoplasias Pulmonares , Técnicas de Amplificación de Ácido Nucleico , Humanos , Exosomas/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Biopsia Líquida/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Aptámeros de Nucleótidos , Biomarcadores de Tumor/genética , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentaciónRESUMEN
Saline-alkali land is an important cultivated land reserve resource for tackling global climate change and ensuring food security, partly because it can store large amounts of carbon (C). However, it is unclear how saline-alkali land reclamation (converting saline-alkali land into cultivated land) affects soil C storage. We collected 189 adjacent pairs of salt-affected and cultivated soil samples (0-30 cm deep) from the Songnen Plain, eastern coastal area, Hetao Plain, and northwestern arid area in China. Various soil properties, the soil inorganic C (SIC), organic C (SOC), particulate organic C (POC), and mineral-associated organic C (MAOC) densities, and plant- and microbial-derived C accumulation were determined. Saline-alkali land reclamation inconsistently affected the SIC density but significantly (P < 0.001) increased the SOC density. The SOC, POC, and MAOC densities were predicted well by the integrative soil amelioration index. Saline-alkali land reclamation significantly increased plant-derived C accumulation and the plant-derived C to microbial-derived C ratios in all saline-alkali areas, and less microbial transformation of plant-derived C (i.e., less lignin degradation or oxidation) occurred in cultivated soils than salt-affected soils. The results indicated that saline-alkali land reclamation leads to plant-derived C becoming the dominant contributor of SOC storage. POC storage and MAOC storage were strongly linked to plant- and microbial-derived C accumulation, respectively, caused by saline-alkali land reclamation. Our findings suggest that saline-alkali land reclamation increases C storage in topsoil by preferentially promoting plant-derived C accumulation.
RESUMEN
In this study, we systematically investigated the interactions between Cu2+ and various biomolecules, including double-stranded DNA, Y-shaped DNA nanospheres, the double strand of the hybridization chain reaction (HCR), the network structure of cross-linked HCR (cHCR), and small molecules (PPi and His), using Cu2+ as an illustrative example. Our research demonstrated that the coordination between Cu2+ and these biomolecules not only is suitable for modulating luminescent material signals through complexation reactions with Cu2+ but also enhances signal intensities in materials based on chemical reactions by increasing spatial site resistance and local concentration. Building upon these findings, we harnessed the potential for signal amplification in self-assembled DNA nanospheres and the selective complexation modulation of calcein in conjunction with the aptamer targeting mucin 1 as a recognition probe. We applied this approach to the analysis of circulating tumor cells, with the lung cancer cell line A549 serving as a representative model. Our assay, utilizing both a fluorometer and a handheld detector, achieved impressive detection limits of ag/ml and single-cell levels for mucin 1 and A549 cells, and this approach was successfully validated using 46 clinical samples, yielding 100% specificity and 86.5% sensitivity. Consequently, our strategy has paved the way for more portable and precise disease diagnosis.
RESUMEN
Background: Systemic lupus erythematosus (SLE) is a multi-organ chronic autoimmune disease. Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract. Previous studies have shown that SLE and IBD share common pathogenic pathways and genetic susceptibility, but the specific pathogenic mechanisms remain unclear. Methods: The datasets of SLE and IBD were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the Limma package. Weighted gene coexpression network analysis (WGCNA) was used to determine co-expression modules related to SLE and IBD. Pathway enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for co-driver genes. Using the Least AbsoluteShrinkage and Selection Operator (Lasso) regressionand Support Vector Machine-Recursive Feature Elimination (SVM-RFE), common diagnostic markers for both diseases were further evaluated. Then, we utilizedthe CIBERSORT method to assess the abundance of immune cell infiltration. Finally,we used the single-cell analysis to obtain the location of common diagnostic markers. Results: 71 common driver genes were identified in the SLE and IBD cohorts based on the DEGs and module genes. KEGG and GO enrichment results showed that these genes were closely associated with positive regulation of programmed cell death and inflammatory responses. By using LASSO regression and SVM, five hub genes (KLRF1, GZMK, KLRB1, CD40LG, and IL-7R) were ultimately determined as common diagnostic markers for SLE and IBD. ROC curve analysis also showed good diagnostic performance. The outcomes of immune cell infiltration demonstrated that SLE and IBD shared almost identical immune infiltration patterns. Furthermore, the majority of the hub genes were commonly expressed in NK cells by single-cell analysis. Conclusion: This study demonstrates that SLE and IBD share common diagnostic markers and pathogenic pathways. In addition, SLE and IBD show similar immune cellinfiltration microenvironments which provides newperspectives for future treatment.
Asunto(s)
Biomarcadores , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Enfermedades Inflamatorias del Intestino , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/inmunología , Transcriptoma , Biología Computacional/métodos , Ontología de Genes , Bases de Datos GenéticasRESUMEN
Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1). This approach employs high-affinity aptamers as specific recognition elements, utilizes rolling circle amplification and DNA nanospheres as effective bridges and signal amplifiers, and leverages methylene blue (MB) and doxorubicin (DOX) as robust signal reporters. The crux of this separation- and label-free method is the specific response of MB and DOX to G-quadruplex structures and DNA nanospheres, respectively. Quantifying TDEs using this strategy enabled precise discrimination of lung cancer patients (n = 25) from healthy donors (n = 12), showing 100% specificity (12/12), 92% sensitivity (23/25), and an overall accuracy of 94.6% (35/37), with an area under the receiver operating characteristic curve (AUC) of 0.97. Furthermore, the assay results strongly correlated with findings from computerized tomography and pathological analyses. Our approach could facilitate the early diagnosis of lung cancer through TDEs-based liquid biopsy.
Asunto(s)
Aptámeros de Nucleótidos , Antígeno B7-H1 , Técnicas Biosensibles , Doxorrubicina , Técnicas Electroquímicas , Exosomas , Neoplasias Pulmonares , Humanos , Técnicas Biosensibles/métodos , Exosomas/química , Técnicas Electroquímicas/métodos , Neoplasias Pulmonares/química , Aptámeros de Nucleótidos/química , Doxorrubicina/química , ADN/química , Azul de Metileno/química , Nanosferas/química , G-CuádruplexRESUMEN
Mutations near allosteric sites can have a significant impact on the function of KRAS. Three specific mutations, K104Q, G12D/K104Q, and G12D/G75A, which are located near allosteric positions, were selected to investigate the molecular mechanisms behind mutation-induced influences on the activity of KRAS. Gaussian accelerated molecular dynamics (GaMD) simulations followed by the principal component analysis (PCA) were performed to improve the sampling of conformational states. The results revealed that these mutations significantly alter the structural flexibility, correlated motions, and dynamic behavior of the switch regions that are essential for KRAS binding to effectors or regulators. Furthermore, the mutations have a significant impact on the hydrogen bonding interactions between GDP and the switch regions, as well as on the electrostatic interactions of magnesium ions (Mg2+) with these regions. Our results verified that these mutations strongly influence the binding of KRAS to its effectors or regulators and allosterically regulate the activity. We believe that this work can provide valuable theoretical insights into a deeper understanding of KRAS function.Communicated by Ramaswamy H. Sarma.
RESUMEN
Herein, we propose a paper-based laboratory via enzyme-free nucleic acid amplification and nanomaterial-assisted cation exchange reactions (CERs) assisted single-cell-level analysis (PLACS). This method allowed for the rapid detection of mucin 1 and trace circulating tumor cells (CTCs) in the peripheral blood of lung cancer patients. Initially, an independently developed method requiring one centrifuge, two reagents (lymphocyte separation solution and erythrocyte lysate), and a three-step, 45 min sample pretreatment was employed. The core of the detection approach consisted of two competitive selective identifications: copper sulfide nanoparticles (CuS NPs) to C-Ag+-C and Ag+, and dual quantum dots (QDs) to Cu2+ and CuS NPs. To facilitate multimodal point-of-care testing (POCT), we integrated solution visualization, test strip length reading, and a self-developed hand-held fluorometer readout. These methods were detectable down to ag/mL of mucin 1 concentration and the single-cell level. Forty-seven clinical samples were assayed by fluorometer, yielding 94% (30/32) sensitivity and 100% (15/15) specificity with an area under the curve (AUC) of 0.945. Nine and 15 samples were retested by a test strip and hand-held fluorometer, respectively, with an AUC of 0.95. All test results were consistent with the clinical imaging and the folate receptor (FR)-PCR kit findings, supporting its potential in early diagnosis and postoperative monitoring.
Asunto(s)
Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/patología , Mucina-1/genética , Biopsia Líquida , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Long noncoding RNAs (lncRNAs) have emerged as crucial regulators across diverse biological processes and diseases. While high-throughput sequencing has enabled lncRNA discovery, functional characterization remains limited. The EVLncRNAs database is the first and exclusive repository for all experimentally validated functional lncRNAs from various species. After previous releases in 2018 and 2021, this update marks a major expansion through exhaustive manual curation of nearly 25 000 publications from 15 May 2020, to 15 May 2023. It incorporates substantial growth across all categories: a 154% increase in functional lncRNAs, 160% in associated diseases, 186% in lncRNA-disease associations, 235% in interactions, 138% in structures, 234% in circular RNAs, 235% in resistant lncRNAs and 4724% in exosomal lncRNAs. More importantly, it incorporated additional information include functional classifications, detailed interaction pathways, homologous lncRNAs, lncRNA locations, COVID-19, phase-separation and organoid-related lncRNAs. The web interface was substantially improved for browsing, visualization, and searching. ChatGPT was tested for information extraction and functional overview with its limitation noted. EVLncRNAs 3.0 represents the most extensive curated resource of experimentally validated functional lncRNAs and will serve as an indispensable platform for unravelling emerging lncRNA functions. The updated database is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs3/.
Asunto(s)
Bases de Datos de Ácidos Nucleicos , ARN Largo no Codificante , Manejo de Datos , Almacenamiento y Recuperación de la Información , ARN Largo no Codificante/genéticaRESUMEN
TiO2 photocatalysts are of great interest in the fields of environmental purification, new energy and so on, because of their non-toxicity, high stability, high redox ability and low cost. However, the photogenerated carriers are severely recombined, which limits the application of TiO2 photocatalysts. Herein, S-scheme Cu3P/TiO2 heterojunction composites were successfully synthesized by a simple and efficient microwave hydrothermal method, and the results show that the hydrogen production rate of Cu3P/TiO2 is 5.83 mmolâg-1âh-1 under simulated sunlight irradiation, which is 7.3 and 83.3 times higher than that of pure TiO2 and Cu3P, respectively. This excellent performance is derived from the internal electric field (IEF) and energy band bending generated by the S-scheme heterojunction formed between Cu3P and TiO2. The density functional theory (DFT) calculation indicates that the Cu3P possess smaller work function and more negative conduction band (CB) position than that of TiO2, which is very conducive to greatly improve the H+ reduction ability and hydrogen production performance. This work provides a new idea for the reveal of electron transfer paths and active sites in S-scheme heterojunctions and deepens the mechanism understanding.
RESUMEN
The spliceosomal snRNP cores, each comprised of a snRNA and a seven-membered Sm ring (D1/D2/F/E/G/D3/B), are assembled by twelve chaperoning proteins in human. However, only six assembly-assisting proteins, ICln and the SMN complex (SMN/Gemin2/Gemin6-8), have been found in Schizosaccharomyces pombe (Sp). Here, we used recombinant proteins to reconstitute the chaperone machinery and investigated the roles of these proteins systematically. We found that, like the human system, the assembly in S. pombe requires ICln and the SMN complex sequentially. However, there are several significant differences. For instance, h_F/E/G forms heterohexamers and heterotrimers, while Sp_F/E/G only forms heterohexamers; h_Gemin2 alone can bind D1/D2/F/E/G, but Sp_Gemin2 cannot. Moreover, we found that Sp_Gemin2 is essential using genetic approaches. These mechanistic studies reveal that these six proteins are necessary and sufficient for Sm core assembly at the molecular level, and enrich our understanding of the chaperone systems in species variation and evolution.
RESUMEN
Natural polysaccharides are macromolecular substances with great potential owing to their wide biological activity and low toxicity. However, not all polysaccharides have significant pharmacodynamic activity; hence, appropriate chemical modification methods can be selected according to the unique structural characteristics of polysaccharides to assist in enhancing and promoting the presentation of their biological activities. This review summarizes research progress on modified polysaccharides, including common chemical modification methods, the change in biological activity following modification, and the factors affecting the biological activity of chemically modified polysaccharides. At the same time, the difficulties and challenges associated with the structural modification of natural polysaccharides are also outlined in this review. Thus, research on polysaccharide structure modification is critical for improving the development and utilization of sugar products.
Asunto(s)
Polisacáridos , Polisacáridos/farmacología , Relación Estructura-ActividadRESUMEN
Nanoparticulate-Nd2O3 (nano-Nd2O3) has been excessively utilized in agriculture, industry, and medicine. Hence, nano-Nd2O3 can have environmental implications. However, the impact of nano-Nd2O3 on alpha diversity, composition, and function of soil bacterial communities has not been thoroughly evaluated. We amended soil to achieve different concentrations of nano-Nd2O3 (0, 10, 50, and 100 mg kg-1 soil) and incubated the mesocosms for 60 days. On days 7 and 60 of the experiment, we measured the effect of nano-Nd2O3 on alpha diversity and composition of soil bacterial community. Further, the effect of nano-Nd2O3 on the function of soil bacterial community was assessed based on changes in the activities of the six potential enzymes that mediate the cycling of nutrients in the soil. Nano-Nd2O3 did not alter the alpha diversity and composition of the soil bacterial community; however, it negatively affected community function in a dose-dependent manner. Specifically, the activities of ß-1,4-glucosidase and ß-1,4-n-acetylglucosaminidase that mediate soil carbon and nitrogen cycling, respectively, were significantly affected on days 7 and 60 of the exposure. The effect of nano-Nd2O3 on the soil enzymes correlated with changes in relative abundances of the rare and sensitive taxa, viz., Isosphaerales, Isosphaeraceae, Ktedonobacteraceae, and Streptomyces. Overall, we provide information for the safe implementation of technological applications that use nano-Nd2O3.
Asunto(s)
Chloroflexi , Suelo , Microbiología del Suelo , Agricultura , BacteriasRESUMEN
Hundreds of plant species have been domesticated to feed human civilization, while some crops have undergone de-domestication into agricultural weeds, threatening global food security. To understand the genetic and epigenetic basis of crop domestication and de-domestication, we generated DNA methylomes from 95 accessions of wild rice (Oryza rufipogon L.), cultivated rice (Oryza sativa L.) and weedy rice (O. sativa f. spontanea). We detected a significant decrease in DNA methylation over the course of rice domestication but observed an unexpected increase in DNA methylation through de-domestication. Notably, DNA methylation changes occurred in distinct genomic regions for these 2 opposite stages. Variation in DNA methylation altered the expression of nearby and distal genes through affecting chromatin accessibility, histone modifications, transcription factor binding, and the formation of chromatin loops, which may contribute to morphological changes during domestication and de-domestication of rice. These insights into population epigenomics underlying rice domestication and de-domestication provide resources and tools for epigenetic breeding and sustainable agriculture.
Asunto(s)
Domesticación , Oryza , Humanos , Oryza/genética , Variación Genética , Metilación de ADN/genética , Evolución Molecular , Cromatina/genéticaRESUMEN
The Three-River Headwaters region is a hotspot for studying the response of soil function to climate change. To study the horizontal variation characteristics of alpine grassland soil function and vertical changes along soil genetic horizons, soil functional indicators (including respiration, nitrogen conversion rate, and enzymatic activity) of different genetic horizons in alpine grassland soil profiles and their correlations with environmental factors were analyzed. The results showed that there were no significant differences in soil functional characteristics between alpine meadows and steppes, and topsoil had higher respiration rates, nitrogen conversion rates, and enzymatic activities than those of subsoil. Total nitrogen was a key driver of soil functional characteristics in different genetic horizons, explaining 18.3%, 21.4%, and 27.5% of the horizontal variation in functional characteristics, respectively. Climate and vegetation factors mainly affected soil function indirectly by changing soil physicochemical properties in topsoil, but atmospheric nitrogen deposition still affected soil function in subsoil. These results indicate the significant nitrogen limitation of alpine grassland soil in the Three-River Headwaters region, and the findings provide a new insight into the maintenance of soil functional diversity and the response to climate change in the context of global climate change.
RESUMEN
Understanding the mechanisms of biological invasion is critical to biodiversity protection. Previous studies have produced inconsistent relationships between native species richness and invasibility, referred to as the invasion paradox. Although facilitative interactions among species have been proposed to explain the non-negative diversity-invasibility relationship, little is known about the facilitation of plant-associated microbes in invasions. We established a two-year field biodiversity experiment with a native plant species richness gradient (1, 2, 4, or 8 species) and analyzed the effects of community structure and network complexity of leaf bacteria on invasion success. Our results indicated a positive relationship between invasibility and network complexity of leaf bacteria of the invader. Consistent with previous studies, we also found that native plant species richness increased the leaf bacterial diversity and network complexity. Moreover, the results of the leaf bacteria community assembly of the invader suggested that the complex bacteria community resulted from higher native diversity rather than higher invader biomass. We concluded that increased leaf bacterial network complexity along the native plant diversity gradient likely facilitated plant invasion. Our findings provided evidence of a potential mechanism by which microbes may affect the plant community invasibility, hopefully helping to explain the non-negative relationship between native diversity and invasibility.
RESUMEN
Soil respiration and extracellular enzyme activity are important components of the material cycle of mountain ecosystems and play key roles in maintaining ecosystem functions. To explore the coupling relationship between soil functions and environmental factors, the soil functional indicators, environmental factors, and effects of altitude on the soil function of 36 soil samples from 12 altitudes of the Meili Mountain were analyzed. The results showed that there were significant differences in soil respirations and enzyme activities among altitudes of Meili Mountain, and high-altitude areas had higher soil functions. Soil functions increased with altitudinal difference. PCA analysis showed that the first three axes explained 56.7%, 17.4%, and 8.7% of the variance in soil functional elevation change, respectively, indicating that the functional changes related to carbon and phosphorus were higher than those related to nitrogen. There were significant correlations between environmental factors and soil functional indicators; soil function indicators had stronger correlations with soil physicochemical properties than with climatic factors. Altitude mainly affected soil function indirectly by affecting soil physicochemical properties and climatic factors. These results have great scientific significance for improving the understanding of the material cycle and ecological function of the Meili Mountain ecosystem and provide an important reference for in-depth study of the altitude distribution pattern and evolution characteristics of the soil function of the mountain ecosystem.
RESUMEN
Soil bacteria, which are active in shrub encroachment, play key roles in regulating ecosystem structure and function. However, the differentiation characteristics and assembly process of bacterial communities in scrubbed grasslands remain unknown. Taking the Qinghai-Tibet Plateau, a hotspot of shrub encroachment, as the study area, we collected 192 soils near nine natural typical shrubs' roots on a trans-longitude transect (about 1800 km) and investigated the bacterial communities using 16S rRNA amplicon sequencing. We found that the bacterial communities exhibited plant-specific and geographic-specific differentiation. On the one hand, bacterial communities differed significantly across plant species, with widely distributed shrubs harboring high diversity communities but few plant-specific taxa, and narrowly distributed shrubs possessing low diversity communities but more plant-specific taxa. Besides, there was a significant negative correlation between bacterial community similarity and plant phylogenetic distance. On the other hand, bacterial communities differed across geographic sites, with a significant decay in bacterial community similarity with geographic distance. The bacterial alpha diversity varied in an inverted V-shape from west to east, peaking at 91°E, which could be largely driven by mean annual temperature, soil pH and soil total carbon content. Community differentiation increased with the heterogeneity degree of assembly processes, and the dominant assembly process in these two specific differentiations differed. Dominated by stochastic and deterministic forces, respectively, geography diverged bacterial communities primarily through increased dispersal limitation, whereas plants diverged bacterial communities primarily through increased variable selection. Our study provides new insight into the characteristics and mechanisms of root-surrounding soil bacteria differentiation in scrubbed grasslands, contributing to the scientific management of degraded grasslands and the prediction of bacterial community structure and ecosystem function in response to global change.
Asunto(s)
Ecosistema , Suelo , Suelo/química , Tibet , Filogenia , Biodiversidad , ARN Ribosómico 16S , Plantas , Bacterias , Microbiología del SueloRESUMEN
The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Neoplasias Cutáneas/genética , Microambiente Tumoral/genética , Medición de Riesgo , Melanoma Cutáneo MalignoRESUMEN
Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9+ progenitors by activating the Wnt/ß-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.
RESUMEN
Many QTL have been identified for grain appearance quality by linkage analysis (LA) in bi-parental mapping populations and by genome-wide association study (GWAS) in natural populations in rice. However, few of the well characterized genes/QTL have been successfully applied in molecular rice breeding due to genetic background (GB) and environment effects on QTL expression and deficiency of favorable alleles. In this study, GWAS and LA were performed to identify QTL for five grain appearance quality-related traits using three multi-parent advanced generation inter-cross (MAGIC) populations. A total of 22 QTL on chromosomes 1-3, 5-8 were identified by GWAS for five traits in DC1, DC2 and 8way, and four combined populations DC12 (DC1+DC2), DC18 (DC1+8way), DC28 (DC2+8way) and DC128 (DC1+DC2+8way). And a total of 42 QTL were identified on all 12 chromosomes except 10 by LA in the three single populations. Among 20 QTL identified by GWAS in DC1, DC2 and 8way, 10, four and three QTL were commonly detected in DC18, DC28, and DC128, respectively. Similarly, among 42 QTL detected by LA in the three populations, four, one and two QTL were commonly detected in DC18, DC28, and DC128, respectively. There was no QTL mapped together in DC12 by both two mapping methods, indicating that GB could greatly affect the mapping results, and it was easier to map the common QTL among populations with similar GB. The 8way population was more powerful for QTL mapping than the DC1, DC2 and various combined populations. Compared with GWAS, LA can not only identify large-effect QTL, but also identify minor-effect ones. Among 11 QTL simultaneously detected by the two methods in different GBs and environments, eight QTL corresponded to known genes, including AqGL3b and AqGLWR3a for GL and GLWR, AqGW5a, AqGLWR5, AqDEC5 and AqPGWC5 for GW, GLWR, DEC and PGWC, and AqDEC6b and AqPGWC6b for DEC and PGWC, respectively. AqGL7, AqGL3c/AqGLWR3b, AqDEC6a/AqPGWC6a, and AqPGWC7 were newly identified and their candidate genes were analyzed and inferred. It was discussed to further improve grain appearance quality through designed QTL pyramiding strategy based on the stable QTL identified in the MAGIC populations.