Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients ...remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.
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•Living biobank with 80 tumor organoids was derived from treatment-naive CRC patients•Tumor organoids recapitulate histological and genetic features of original tumors•Interpatient variability in the PDO response to chemoradiation treatments•PDOs can predict locally advanced rectal cancer patient responses in the clinic
Yao et al. generated a patient-derived organoid (PDO) biobank from patients with locally advanced rectal cancer (LARC) and reported that organoids had similar molecular profiles to those of the patient tumor and that PDOs can predict LARC patient chemoradiation responses, reinforcing their value as a companion diagnostic tool in LARC treatment.
Structural variations (SVs) and gene copy number variations (gCNVs) have contributed to crop evolution, domestication, and improvement. Here, we assembled 31 high-quality genomes of genetically ...diverse rice accessions. Coupling with two existing assemblies, we developed pan-genome-scale genomic resources including a graph-based genome, providing access to rice genomic variations. Specifically, we discovered 171,072 SVs and 25,549 gCNVs and used an Oryza glaberrima assembly to infer the derived states of SVs in the Oryza sativa population. Our analyses of SV formation mechanisms, impacts on gene expression, and distributions among subpopulations illustrate the utility of these resources for understanding how SVs and gCNVs shaped rice environmental adaptation and domestication. Our graph-based genome enabled genome-wide association study (GWAS)-based identification of phenotype-associated genetic variations undetectable when using only SNPs and a single reference assembly. Our work provides rich population-scale resources paired with easy-to-access tools to facilitate rice breeding as well as plant functional genomics and evolutionary biology research.
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•De novo assembly of 31 high-quality genomes for genetically diverse accessions•Pan-genome-scale resources and a graph-based genome reveal hidden SVs and gCNVs•The derived state of O. sativa SVs was inferred using the O. glaberrima assembly•SVs and gCNVs have shaped gene expression profiles and agronomic trait variations
A high-quality rice pan-genome of genetically diverse rice accessions is constructed through de novo genome assemblies, demonstrating the impact of structural variation and gene copy number variations on environmental adaptations and agronomic traits.
Fault diagnosis is essential for high energy systems such as liquid rocket engines (LREs) due to harsh thermal and mechanical working environment. In this study, a novel method based on one-dimension ...Convolutional Neural Network (1D-CNN) and interpretable bidirectional Long Short-term Memory (LSTM) is proposed for intelligent fault diagnosis of LREs. 1D-CNN is responsible for extracting sequential signals collected from multi sensors. Then the interpretable LSTM is developed to model the extracted features, which contributes to modeling the temporal information. The proposed method was executed for fault diagnosis using the simulated measurement data of the LRE mathematical model. The results demonstrate the proposed algorithm outperforms other methods in terms of accuracy of fault diagnosis. Through experimental verification, the method proposed in this paper was compared with CNN, 1DCNN-SVM and CNN-LSTM in terms of LRE startup transient fault recognition performance. The model proposed in this paper had the highest fault recognition accuracy (97.39%).
A strategy that informs on countries' potential losses due to lack of climate action may facilitate global climate governance. Here, we quantify a distribution of mitigation effort whereby each ...country is economically better off than under current climate pledges. This effort-sharing optimizing approach applied to a 1.5 °C and 2 °C global warming threshold suggests self-preservation emissions trajectories to inform NDCs enhancement and long-term strategies. Results show that following the current emissions reduction efforts, the whole world would experience a washout of benefit, amounting to almost 126.68-616.12 trillion dollars until 2100 compared to 1.5 °C or well below 2 °C commensurate action. If countries are even unable to implement their current NDCs, the whole world would lose more benefit, almost 149.78-791.98 trillion dollars until 2100. On the contrary, all countries will be able to have a significant positive cumulative net income before 2100 if they follow the self-preservation strategy.
Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a ...prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.
From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.
Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3-7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio HR, 10.98; 95%CI, 5.31-22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39-30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79-95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.
Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.
A delayed reaction-diffusion-advection equation subject to constant-flux and free-flow boundary conditions is considered, which models single population dynamics in a river. At first, we show the ...existence of a nonconstant steady state induced by the change of constant flux value. Then by analyzing the distribution of eigenvalues, the stability of the constant and nonconstant steady states and the existence of Hopf bifurcations are obtained. And an algorithm for determining the direction and stability of Hopf bifurcations is derived by applying the center manifold theory and normal form method for PFDEs. Finally, the effects of advection and downstream boundary condition on periodic oscillations are discussed theoretically and numerically.
Auextic materials possessing negative Poisson's ratios have gained great research interest by virtue of its various exotic mechanical properties while most of these metamaterials rely on the hollow ...cellular configuration, largely undermining the overall mechanical performance. It therefore restricts their application in load-bearing engineering fields. In order to solve this issue, we first designed a new class of chiral structures by integrating various polynomial curves. Based on the state-of-the-art 3D printing technique, these auxetic geometries were then fabricated into high-performance composites with chopped carbon fiber (CF) as the reinforcement. Guided by experimental characterization and finite element analysis, the influences of the polynomial orders (n) and the incorporation of CF on the mechanical properties were systematically studied. Results showed that the auxetic behaviour can be tailored by varying the n value inside the polynomial equation. Moreover, the tensile modulus, strength and energy absorption at break of printed chiral samples were all enhanced with the addition of CF, especially for the large improvement of modulus and absorbed energy by 2-fold. Hence, these novel chiral composites present great potential in the development of high performance mechanical metamaterials.
We explore CaCO3 mineralization via the addition of a Ca(OH)2 solution to branched polyethylenimine–CO2 (PEI-CO2) adduct solutions. The alkylammonium carbamate zwitterions (i.e., CO2-adducted ...linkages) in PEI-CO2 adducts can hydrolyze to release bicarbonate ions to form CaCO3in situ; meanwhile, the zwitterions themselves transform into the polyamine structure of polyethylenimine (PEI). The PEI-CO2 polymer serves as both the CO2 source and template for vaterite CaCO3 nucleation and growth. A relatively low dosage of the Ca(OH)2 solution (e.g., at 9.2–37% stoichiometry) preserves enough CO2-adducted linkages in the templating PEI-based chains, allowing them to firmly adsorb onto the growing vaterite nanocrystallites, providing long-term vaterite phase and colloidal stability. The high molecular weight of the used PEIs (e.g., 10 k–25 k Da) strengthens the adsorption as well. The mesoporous structure, the dissolution in a weakly acidic environment (pH 6.5), the low cytotoxicity, the ease of endocytosis, and the presence of reactive PEI amino groups all make the obtained vaterite nanoparticles a versatile candidate for effective and acid-responsive drug delivery. This work highlights the multifunctionality of PEI-CO2 adducts for CaCO3 mineralization, serving as a CO2 source and vaterite template and providing the vaterite phase and colloid stability, as well as reactivity for further modification.
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•PEI-CO2 adducts react with Ca(OH)2 for synthesis of vaterite nanospheres.•Vaterite nucleation and early growth is confined within the PEI-based chains.•PEI-CO2 adducts provide long-term vaterite phase and colloidal stability.•The vaterite nanospheres possess reactive amino group from PEI for further modification.
The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease 9 (CRISPR/Cas9) system has emerged as a promising technology for specific genome editing in many ...species. Here we constructed one vector targeting eight agronomic genes in rice using the CRISPR/Cas9 multiplex genome editing system. By subsequent genetic transformation and DNA sequencing, we found that the eight target genes have high mutation efficiencies in the T
generation. Both heterozygous and homozygous mutations of all editing genes were obtained in T
plants. In addition, homozygous sextuple, septuple, and octuple mutants were identified. As the abundant genotypes in T
transgenic plants, various phenotypes related to the editing genes were observed. The findings demonstrate the potential of the CRISPR/Cas9 system for rapid introduction of genetic diversity during crop breeding.
Compared to quartz, the infrared stimulated luminescence (IRSL) of K-feldspar saturates at higher dose, which has great potential for extending the dating limit. However, dating applications with ...K-feldspar has been hampered due to anomalous fading of the IRSL signal. The post-IR IRSL (pIRIR) signal of K-feldspar stimulated at a higher temperature after a prior low-temperature IR stimulation has significantly lower fading rate. Different dating protocols have been proposed with the pIRIR signals and successful dating applications have been made. In this study, we review the development of various pIRIR dating protocols, and compare their performance in estimating the equivalent dose (D
). Standard growth curves (SGCs) of the pIRIR signals of K-feldspar are introduced. Single-grain K-feldspar pIRIR dating is presented and the existing problems are discussed.
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