EXGEP: a framework for predicting genotype-by-environment interactions using ensembles of explainable machine-learning models.

Phenotypic variation results from the combination of genotype, the environment, and their interaction. The ability to quantify the relative contributions of genetic and environmental factors to complex traits can help in breeding crops with superior adaptability for growth in varied environments. Here, we developed and extensively evaluated the performance of an explainable machine-learning framework named explainable genotype-by-environment interactions prediction (EXGEP) to accurately predict the grain yield in crops.

Valence Tautomerism and Alkaline Properties of Global Aromatic Imine- and Methine-Bridged all-Benzenoid Macrocyclic Superpyrazine and Supertriazine.

The comprehensive understanding of the ground-state electronic structures of all-benzenoid macrocycles and their charged species, particularly those exhibiting global (anti)aromaticity, remains poorly resolved. Here, we present two imine- and methine-bridged all-benzenoid [6]cyclo-para-phenylenes SPAZ (superpyrazine) and STAZ (supertriazine)-designed as π-extended analogues of 1,4-pyrazine and 1,3,5-triazine, respectively. For the first time, we elucidate their unprecedented valence tautomerism between "super-Kekulé" alternating benzenoid/quinoidal structures and a "super-sextet" transient structure, mediated by a 30π azaannulene conjugated pathway.

Unveiling Salt Tolerance Mechanisms in Plants: Integrating the KANMB Machine Learning Model With Metabolomic and Transcriptomic Analysis.

Salt stress presents a substantial threat to cereal crop productivity, especially in coastal agricultural regions where salinity levels are high. Addressing this challenge requires innovative approaches to uncover genetic resources that support molecular breeding of salt-tolerant crops. In this study, a novel machine learning model, KANMB is introduced, designed to analyze integrated multi-omics data from the natural halophyte Spartina alterniflora under various NaCl concentrations.

Fast-forwarding plant breeding with deep learning-based genomic prediction.

Deep learning-based genomic prediction (DL-based GP) has shown promising performance compared to traditional GP methods in plant breeding, particularly in handling large, complex multi-omics data sets. However, the effective development and widespread adoption of DL-based GP still face substantial challenges, including the need for large, high-quality data sets, inconsistencies in performance benchmarking, and the integration of environmental factors. Here, we summarize the key obstacles impeding the development of DL-based GP models and propose future developing directions, such as modular approaches, data augmentation, and advanced attention mechanisms.

Leveraging Automated Machine Learning for Environmental Data-Driven Genetic Analysis and Genomic Prediction in Maize Hybrids.

Genotype, environment, and genotype-by-environment (G×E) interactions play a critical role in shaping crop phenotypes. Here, a large-scale, multi-environment hybrid maize dataset is used to construct and validate an automated machine learning framework that integrates environmental and genomic data for improved accuracy and efficiency in genetic analyses and genomic predictions. Dimensionality-reduced environmental parameters (RD_EPs) aligned with developmental stages are applied to establish linear relationships between RD_EPs and traits to assess the influence of environment on phenotype.

miR-495 promotes intestinal epithelial cell apoptosis through downregulation of Sphingosine-1-phosphate.

Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA.

Interaction between microRNA-195 and HuR regulates Paneth cell function in the intestinal epithelium by altering SOX9 translation.

Paneth cells at the bottom of small intestinal crypts secrete antimicrobial peptides, enzymes, and growth factors and contribute to pathogen clearance and maintenance of the stem cell niche. Loss of Paneth cells and their dysfunction occur commonly in various pathologies, but the mechanism underlying the control of Paneth cell function remains largely unknown. Here, we identified microRNA-195 (miR-195) as a repressor of Paneth cell development and activity by altering SOX9 translation via interaction with RNA-binding protein HuR.

Exploring salt tolerance mechanisms using machine learning for transcriptomic insights: case study in .

Salt stress poses a significant threat to global cereal crop production, emphasizing the need for a comprehensive understanding of salt tolerance mechanisms. Accurate functional annotations of differentially expressed genes are crucial for gaining insights into the salt tolerance mechanism. The challenge of predicting gene functions in under-studied species, especially when excluding infrequent GO terms, persists.

The Spartina alterniflora genome sequence provides insights into the salt-tolerance mechanisms of exo-recretohalophytes.

Spartina alterniflora is an exo-recretohalophyte Poaceae species that is able to grow well in seashore, but the genomic basis underlying its adaptation to salt tolerance remains unknown. Here, we report a high-quality, chromosome-level genome assembly of S. alterniflora constructed through PacBio HiFi sequencing, combined with high-throughput chromosome conformation capture (Hi-C) technology and Illumina-based transcriptomic analyses.

Deep learning-enabled discovery and characterization of HKT genes in Spartina alterniflora.

Spartina alterniflora is a halophyte that can survive in high-salinity environments, and it is phylogenetically close to important cereal crops, such as maize and rice. It is of scientific interest to understand why S. alterniflora can live under such extremely stressful conditions.

Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR.

Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls.

Long noncoding RNA uc.230/CUG-binding protein 1 axis sustains intestinal epithelial homeostasis and response to tissue injury.

Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.

Circular RNA CircHIPK3 Promotes Homeostasis of the Intestinal Epithelium by Reducing MicroRNA 29b Function.

Background & Aims: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed circles. Although circRNAs influence many biological processes, little is known about their role in intestinal epithelium homeostasis. We surveyed circRNAs required to maintain intestinal epithelial integrity and identified circular homeodomain-interacting protein kinase 3 (circHIPK3) as a major regulator of intestinal epithelial repair after acute injury.

MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of DCLK1.

Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders.

Long Noncoding RNA H19 Impairs the Intestinal Barrier by Suppressing Autophagy and Lowering Paneth and Goblet Cell Function.

Background & Aims: The protective intestinal mucosal barrier consists of multiple elements including mucus and epithelial layers and immune defense; nonetheless, barrier dysfunction is common in various disorders. The imprinted and developmentally regulated long noncoding RNA H19 is involved in many cell processes and diseases. Here, we investigated the role of H19 in regulating Paneth and goblet cells and autophagy, and its impact on intestinal barrier dysfunction induced by septic stress.

Cooperative Repression of Insulin-Like Growth Factor Type 2 Receptor Translation by MicroRNA 195 and RNA-Binding Protein CUGBP1.

Insulin-like growth factor type 2 (IGF2) receptor (IGF2R) recognizes mannose 6-phosphate-containing molecules and IGF2 and plays an important role in many pathophysiological processes, including gut mucosal adaptation. However, the mechanisms that control cellular IGF2R abundance are poorly known. MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) critically regulate gene expression programs in mammalian cells by modulating the stability and translation of target mRNAs.

Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats.

Background: Deficiency of choline, a required nutrient, is related to intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms.

Methods: Male Sprague-Dawley rats (4 weeks old) were fed AIN-93G chow and administered intravenous 0.

CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function.

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown.

Common genetic variations in Patched1 (PTCH1) gene and risk of hirschsprung disease in the Han Chinese population.

Hirschsprung disease (HSCR) is the most frequent genetic cause of congenital intestinal obstruction with an incidence of 1:5000 live births. In a pathway-based epistasis analysis of data generated by genome-wide association study on HSCR, specific genotype of Patched 1 (PTCH1) has been linked to an increased risk for HSCR. The aim of the present study is to examine the contribution of genetic variants in PTCH1 to the susceptibility to HSCR in Han Chinese.

[Optimization of expression conditions of recombinant Fuantai-03 and detection of its biological activities].

Fuantai-03(FAT-03), isolated from the Dasyatis akajei, has a strong antiangiogenic activity. The recombinant Fuantai-03 (GST/rFAT-03) fusion protein can be obtained with the DNA recombination technology. In this study, expression conditions of GST/rFAT-03 were optimized by response surface experimental design method.

Competitive binding of CUGBP1 and HuR to occludin mRNA controls its translation and modulates epithelial barrier function.

RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HuR are highly expressed in epithelial tissues and modulate the stability and translation of target mRNAs. Here we present evidence that CUGBP1 and HuR jointly regulate the translation of occludin and play a crucial role in the maintenance of tight junction (TJ) integrity in the intestinal epithelial cell monolayer. CUGBP1 and HuR competed for association with the same occludin 3'-untranslated region element and regulated occludin translation competitively and in opposite directions.

Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function.

Occludin is a transmembrane tight junction (TJ) protein that plays an important role in TJ assembly and regulation of the epithelial barrier function, but the mechanisms underlying its post-transcriptional regulation are unknown. The RNA-binding protein HuR modulates the stability and translation of many target mRNAs. Here, we investigated the role of HuR in the regulation of occludin expression and therefore in the intestinal epithelial barrier function.