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Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid‐parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over‐parent heterosis or heterobeltiosis). Nonadditive expression and allele‐specific gene expression assays showed that the glutathione S‐transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt‐sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72–OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice. [ABSTRACT FROM AUTHOR]

Summary: Haemoglobin H (Hb H) disease (intermediate status of α‐thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined β‐thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.948C>A, p.S316R) in the PIP4K2A gene in a female Hb H disease patient who displayed moderate anaemia and a relatively high Hb H level. Haematological analysis in her family members revealed that individuals carrying this mutation have upregulated β‐globin expression, leading to a more imbalanced β/α‐globin ratio and more Hb H inclusion bodies in peripheral red blood cells. According to functional experiments, the mutant PIP4K2A protein exhibits enhanced protein stability, increased kinase activity and a stronger regulatory effect on downstream proteins, suggesting a gain‐of‐function mutation. Moreover, introduction of the S316R mutation into HUDEP‐2 cells increased expression of β‐globin, further inhibiting erythroid differentiation and terminal enucleation. Thus, the S316R mutation is a novel genetic factor associated with β‐globin expression, and the PIP4K2A gene is a new potential modifier gene affecting the α‐thalassemia phenotype. [ABSTRACT FROM AUTHOR]

• The expression of AmNTL1 was induced by controlled cold, salt, drought and ABA stresses. • Expressing AmNTL1 in Arabidopsis enhanced tolerance to multiple abiotic stresses and the stress-induced oxidative damage. • Expressing AmNTL1 in Arabidopsis exhibited sensitivity to exogenous ABA. The NTM1-like (NTL) proteins constitute a subfamily of the NAM, ATAF and CUC (NAC) transcription factor family that regulates diverse biological processes including stress response in plants. Ammopiptanthus mongolicus is a desert shrub with very high tolerance to harsh environments. Here, an NTL-like gene, AmNTL1 , was cloned from this species and its function in abiotic stress tolerance was analyzed. AmNTL1 encodes a canonical NTL protein. The full-length protein was primarily located at the plasma membrane and had transactivation activity in yeast. The expression of AmNTL1 was differentially induced by cold, salt, drought, and exogenous abscisic acid (ABA) in laboratory-cultured A. mongolicus seedlings. The expression was also induced by the cold winter and spring weather in leaves of the A. mongolicus shrubs naturally growing in the wild and was at moderate levels in lateral roots, young leaves and flower buds of the shrubs. The transgenic Arabidopsis lines constitutively expressing AmNTL1 showed enhanced tolerance to freezing, chilling, salinity, and osmotic stress as well as chilling- and salt-induced oxidative stresses. The transgenic lines also displayed ABA-sensitive phenotypes at the seed germination stage. These results suggest that AmNTL1 may play an important role in plants coping with abiotic stresses, especially cold injury, through the ABA-dependent signaling pathway. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a complex and refractory malignant tumor, ranking the third cause of cancer-related deaths worldwide. Lenvatinib is currently employed to treat advanced, unresectable HCC as a first-line drug. The purpose of this study was to explore the pharmacological mechanisms of lenvatinib acting on HCC through the analysis of differential expressed genes based on network pharmacology. The target genes of lenvatinib were collected from PubChem, SwissTargetPrediction, PharmMapper, and BATMAN-TCM online public databases. In addition, related gene targets for HCC were obtained using NCBI Gene Expression Omnibus (NCBI-GEO) database. Afterward, the protein-protein interaction (PPI) network was established to visualize and understand the interaction relationships of overlapping gene targets from both lenvatinib and HCC. Furthermore, according to the data obtained, Gene Ontology (GO) analysis indicated that these intersectant genes were mainly enriched in response to xenobiotic stimulus, gland development, ion channel complex, membrane raft, and steroid binding. Besides, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the therapeutic effects of lenvatinib on HCC probably involved bile secretion, MAPK signaling pathway, cGMP-PKG signaling pathway, PI3K-Akt signaling pathway, and Ras signaling pathway. Moreover, a total of six key differential genes, namely, ALB, CCND1, ESR1, AR, CCNA2, and AURKA, were identified as most significant targets associated with lenvatinib treating HCC and further verified by molecular docking, which demonstrated that lenvatinib had a strong binding efficiency with these six key gene-encoded proteins. Taken together, this study systematically provided new insights for researchers to determine the intervention mechanisms of lenvatinib in HCC therapy. [ABSTRACT FROM AUTHOR]

Soil burial is a survival strategy for grapevines that can safely overwinter in north-western regions of China. A suitable training system was beneficial for soil burial to provide winter protection. Moreover, the training system can also significantly affect fruit quality during the development of grape berries, such as primary and secondary metabolites. In this study, four-year-old Cabernet Gernischt grapevines were used as experimental material and exposed to four training systems, including the Ningxia traditional vertical trunk (control, CK); the gobelet (T1); single guyot (T2); slant trunk with vertical shoot positioning (STVSP) (T3). The results showed that total soluble solid total phenol content was 12.69%, 57% higher under T3 training systems than in the control, and T3 alleviated the canopy density, leading to improving the leaf photosynthetic efficiency gas chromatography-mass spectrometry (GC-MS) assay used to detect the aroma compounds. The results indicated that the T3 training system enhanced the accumulation of alcohols, carbonyl compounds, C6/C9 and esters, which account for the largest proportion of volatile compounds, and the qRT-PCR reveals that VvEcar, Vvter, VvCCD1, and VvLis were raised under T3 at the transcriptional level. Moreover, T3 contributes to most free amino acid synthesis. Additionally, the PCA reveals the correlation of free amino acids under four training systems, which reflected the mostly amino acid related to T3, and thus, we could speculate that T3 enhances the overall aroma. These results may lead to new strategies to select a new, short trunk training system to achieve mechanized buried soil, to prevent cold and produce high-quality wine in this area. [ABSTRACT FROM AUTHOR]

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Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with a depressing survival rate. The reprogramming of tumor metabolism was identified as a new hallmark of cancer in tumor microenvironment (TME), and we made a comprehensive exploration to reveal the prognostic role of the metabolic-related genes. Transcriptome profiling data of LUAD were, respectively, downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Based on the extracted metabolic-related genes, a novel 5-gene metabolic prognostic signature (including GNPNAT1, LPGAT1, TYMS, LDHA, and PTGES) was constructed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. This signature confirmed its robustness and accuracy by external validation in multiple databases. It could be an independent risk factor for LUAD, and the nomograms possessed moderately accurate performance with the C-index of 0.755 (95% confidence interval: 0.706–0.804) and 0.691 (95% confidence interval: 0.636–0.746) in training set and testing set. This signature could reveal the metabolic features according to the results of gene set enrichment analysis (GSEA) and meanwhile monitor the status of TME through ESTIMATE scores and the infiltration levels of immune cells. In conclusion, this gene signature is a cost-effective tool which could indicate the status of TME to provide more clues in the exploration of new diagnostic and therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objectives. We aimed to find the key pathways associated with the development of osteoporosis. Methods. We downloaded expression profile data of GSE35959 and analyzed the differentially expressed genes (DEGs) in 3 comparison groups (old_op versus middle, old_op versus old, and old_op versus senescent). KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were carried out. Besides, Venn diagram analysis and gene functional interaction (FI) network analysis were performed. Results. Totally 520 DEGs, 966 DEGs, and 709 DEGs were obtained in old_op versus middle, old_op versus old, and old_op versus senescent groups, respectively. Lysosome pathway was the significantly enriched pathways enriched by intersection genes. The pathways enriched by subnetwork modules suggested that mitotic metaphase and anaphase and signaling by Rho GTPases in module 1 had more proteins from module. Conclusions. Lysosome pathway, mitotic metaphase and anaphase, and signaling by Rho GTPases may be involved in the development of osteoporosis. Furthermore, Rho GTPases may regulate the balance of bone resorption and bone formation via controlling osteoclast and osteoblast. These 3 pathways may be regarded as the treatment targets for osteoporosis. [ABSTRACT FROM AUTHOR]