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Grain weight and grain number, the two important yield traits, are mainly determined by grain size and panicle architecture in rice. Herein, we report the identification and functional analysis of OsSPL4 in panicle and grain development of rice. Using CRISPR/Cas9 system, two elite alleles of OsSPL4 were obtained, which exhibited an increasing number of grains per panicle and grain size, resulting in increase of rice yield. Cytological analysis showed that OsSPL4 could regulate spikelet development by promoting cell division. The results of RNA-seq and qRT-PCR validations also demonstrated that several MADS-box and cell-cycle genes were up-regulated in the mutation lines. Co-expression network revealed that many yield-related genes were involved in the regulation network of OsSPL4. In addition, OsSPL4 could be cleaved by the osa-miR156 in vivo, and the OsmiR156-OsSPL4 module might regulate the grain size in rice. Further analysis indicated that the large-grain allele of OsSPL4 in indica rice might introgress from aus varieties under artificial selection. Taken together, our findings suggested that OsSPL4 could be as a key regulator of grain size by acting on cell division control and provided a strategy for panicle architecture and grain size modification for yield improvement in rice. [ABSTRACT FROM AUTHOR]

Integration of transcriptomics and metabolomics data can provide detailed information for better understanding the molecular mechanisms underlying salt tolerance in rice. In the present study, we report a comprehensive analysis of the transcriptome and metabolome of rice overexpressing the OsDRAP1 gene, which encodes an ERF transcription factor and was previously identified to be conferring drought tolerance. Phenotypic analysis showed that OsDRAP1 overexpression (OE) improved salt tolerance by increasing the survival rate under salt stress. OsDRAP1 affected the physiological indices such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) to enhance redox homeostasis and membrane stability in response to salt stress. Higher basal expression of OsDRAP1 resulted in differential expression of genes that potentially function in intrinsic salt tolerance. A core set of genes with distinct functions in transcriptional regulation, organelle gene expression and ion transport were substantially up-regulated in the OE line in response to salt stress, implying their important role in OsDRAP1-mediated salt tolerance. Correspondingly, metabolome profiling detected a number of differentially metabolites in the OE line relative to the wild type under salt stress. These metabolites, including amino acids (proline, valine), organic acids (glyceric acid, phosphoenolpyruvic acid and ascorbic acid) and many secondary metabolites, accumulated to higher levels in the OE line, demonstrating their role in salt tolerance. Integration of transcriptome and metabolome analysis highlights the crucial role of amino acids and carbohydrate metabolism pathways in OsDRAP1-mediated salt tolerance. [ABSTRACT FROM AUTHOR]

The Chinese tallow tree (Triadica sebifera) can produce oil with high content of unsaturated fatty acids in seeds and shows attractive leaf color in autumn and winter. Here, the 739 Mb chromosome-scale genome sequence of the Chinese tallow tree was assembled and it reveals the Chinese tallow tree is a tetraploid. Numerous genes related to nutrition assimilation, energy utilization, biosynthesis of secondary metabolites and resistance significantly expanded or are specific to the Chinese tallow tree. These genes would enable the Chinese tallow tree to obtain high adaptability. More genes in fatty acids biosynthesis in its genome, especially for unsaturated fatty acids biosynthesis, and higher expression of these genes in seeds would be attributed to its high content of unsaturated fatty acids. Cyanidin 3-O-glucoside was identified as the major component of anthocyanin in red leaves. All structural genes in anthocyanin biosynthesis show significantly higher expression in red leaves than in green leaves. Transcription factors, seven MYB and one bHLH, were predicted to regulate these anthocyanin biosynthesis genes. Collectively, we provided insight into the polyploidization, high adaptability and biosynthesis of the high content of unsaturated fatty acids in seeds and anthocyanin in leaves for the Chinese tallow tree. A chromosome-level assembly of the economically-important Chinese tallow tree is presented alongside functional analyses into biosynthetic products in the leaves and seeds. [ABSTRACT FROM AUTHOR]

Ovarian tumor (OTU) subfamily deubiquitinases are involved in various cellular processes, such as inflammation, ferroptosis and tumorigenesis; however, their pathological roles in prostate cancer (PCa) remain largely unexplored. In this study, we observed that several OTU members displayed genomic amplification in PCa, among which ovarian tumor deubiquitinase 6A (OTUD6A) amplified in the top around 15–20%. Further clinical investigation showed that the OTUD6A protein was highly expressed in prostate tumors, and increased OTUD6A expression correlated with a higher biochemical recurrence risk after prostatectomy. Biologically, wild-type but not a catalytically inactive mutant form of OTUD6A was required for PCa cell progression. In vivo experiments demonstrated that OTUD6A oligonucleotides markedly suppressed prostate tumorigenesis in PtenPC−/− mice and patient-derived xenograft (PDX) models. Mechanistically, the SWI/SNF ATPase subunit Brg1 and the nuclear receptor AR (androgen receptor) were identified as essential substrates for OTUD6A in PCa cells by a mass spectrometry (MS) screening approach. Furthermore, OTUD6A stabilized these two proteins by erasing the K27-linked polyubiquitination of Brg1 and K11-linked polyubiquitination of AR. OTUD6A amplification exhibited strong mutual exclusivity with mutations in the tumor suppressors FBXW7 and SPOP. Collectively, our results indicate the therapeutic potential of targeting OTUD6A as a deubiquitinase of Brg1 and AR for PCa treatment. OTUD6A, a deubiquitinase, is amplified in prostate cancer and correlates with poor survivability, increasing the growth of prostate cancer cell lines and PDX models. OTUD6A stabilizes the expression of Brg1 and AR through the removal of K27- and K11-linked polyubiquination. [ABSTRACT FROM AUTHOR]

Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8–10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 μg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient. [ABSTRACT FROM AUTHOR]

Objectives: A machine learning model was developed to evaluate the severity of aortic coarctation (CoA) in infants based on anatomical features measured on CTA. Methods: In total, 239 infant patients undergoing both thorax CTA and echocardiography were retrospectively reviewed. The patients were assigned to either mild or severe CoA group based on their pressure gradient on echocardiography. They were further divided into patent ductus arteriosus (PDA) and non-PDA groups. The anatomical features were measured on double-oblique multiplanar reconstructed CTA images. Then, the optimal features were identified by using the Boruta algorithm. Subsequently, the coarctation severity was classified using linear discriminant analysis (LDA). We further investigated the relationship between the anatomical features and re-coarctation using Cox regression. Results: Four anatomical features showed significant differences between the mild and severe CoA groups, including the smallest aortic cross-sectional area indexed to body surface area (p < 0.001), the narrowest aortic diameter (CoA diameter) indexed to height (p < 0.001), the diameter of the descending aorta at the diaphragmatic level (p < 0.001) and weight (p = 0.005). With these features, accuracy of 88.6% and 90.2%, sensitivity of 65.0% and 72.1%, and specificity of 92.9% and 100% were obtained for classifying the CoA severity in the non-PDA and PDA groups, respectively. Moreover, CoA diameter indexed to weight was associated with the risk of re-coarctation. Conclusions: CoA severity can be evaluated by using LDA with anatomical features. When quantifying the severity of CoA and risk of re-coarctation, both anatomical alternations at the CoA site and the growth of the patients need to be considered. Key Points: • CTA is routinely ordered for infants with coarctation of the aorta; however, whether anatomical variations observed with CTA could be used to assess the severity of CoA remains unknown. • Using the diameter and area of the coarctation site adjusted to body growth as features, the LDA model achieved an accuracy of 88.6% and 90.2% in differentiating between the mild and severe CoA patients in the non-PDA group and PDA group, respectively. • The narrowest aortic diameter (CoA diameter) indexed to weight has a hazard ratio of 10.29 for re-coarctation. [ABSTRACT FROM AUTHOR]

BACKGROUND: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance. METHODS: Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence. RESULTS: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy. CONCLUSIONS: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.Methods: Kaplan-Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.Results: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.Conclusions: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Salt stress and bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) are key limiting factors of rice (Oryza sativa L.) yields. Members of sucrose non-fermenting 1 (SNF1)-related protein kinase 2 (SnRK2), which is a family of plant-specific Ser/Thr kinases, are important components of signaling pathways involved in plant developmental processes and responses to stresses. There are 10 members of the SnRK2 family in rice; however, their functions are poorly understood, as are the underlying molecular mechanisms. Results: In this study, we found that OsSAPK9, which belongs to the SnRK2 family, positively regulated salt-stress tolerance and strain-specific resistance to bacterial blight in rice. RNA sequencing revealed that there were 404 and 1324 genes differentially expressed in OsSAPK9-RNAi in comparison with wild-type plants under salt-stress conditions and after Xoo inoculation, respectively, which participate in basic metabolic processes. In total, 65 common differentially expressed genes involved mainly in defense responses were detected both under salt-stress conditions and after Xoo inoculation. Moreover, in vivo and in vitro experiments demonstrated that OsSAPK9 forms a protein complex with the molecular chaperones OsSGT1 and OsHsp90, and transgenic plants overexpressing OsSGT1 exhibited decreased tolerances to salt stress and significantly increased resistance levels to bacterial blight. Thus, OsSAPK9 may function as a center node regulator of salt-stress responses and disease-resistance pathways through its interaction with OsSGT1 in rice. Conclusion: This study confirms that OsSAPK9 functions as a positive regulator of salt-stress responses and disease resistance through its interaction with OsSGT1 in rice. [ABSTRACT FROM AUTHOR]

Background: High soil salinity can cause significant losses in rice productivity worldwide, mainly because salt inhibits plant growth and reduces grain yield. To cope with environmental changes, plants have evolved several adaptive mechanisms that involve the regulation of many stress-responsive genes. Results: In this study, we identified OsSTAP1, which encodes an AP2/ERF-type transcription factor, was rapidly induced by ABA, ACC, salt, cold, and PEG treatments. OsSTAP1 is localized to the nucleus and acts as a transcriptional activator in plant cells. Compared with wild type, transgenic lines overexpressing OsSTAP1 exhibited increased tolerance to salt stress with higher SOD, POD, and CAT activities, and lower Na+/K+ ratios in the shoots. In addition, many other stress-responsive genes, including other ERF- and peroxidase-encoding genes, were upregulated in the OsSTAP1-overexpression lines. Conclusion: This study suggests that OsSTAP1 functions as an AP2/ERF transcriptional activator, and plays a positive role in salt tolerance by decreasing the Na+/K+ ratio and maintaining cellular redox homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: To develop and identify a MRI-based radiomics nomogram for the preoperative prediction of parametrial invasion (PMI) in patients with early-stage cervical cancer (ECC).Materials and Methods: All 137 patients with ECC (FIGO stages IB-IIA) underwent T2WI and DWI scans before radical hysterectomy surgery. The radiomics signatures were calculated with the radiomics features which were extracted from T2WI and DWI and selected by the least absolute shrinkage and selection operation regression. The support vector machine (SVM) models were built using radiomics signatures derived from T2WI and joint T2WI and DWI respectively to evaluate the performance of radiomics signatures for distinguishing patients with PMI. A radiomics nomogram was drawn based on the radiomics signatures with a better performance, patient's age, and pathological grade; its discrimination and calibration performances were estimated.Results: For T2WI and joint T2WI and DWI, the radiomics signatures yielded an AUC of 0.797 (95% CI, 0.682-0.911) vs 0.946 (95% CI, 0.899-0.994), and 0.780 (95% CI, 0.641-0.920) vs 0.921 (95% CI, 0.832-1) respectively in the primary and validation cohorts. The radiomics nomogram, integrating the radiomics signatures from joint T2WI and DWI, patient's age, and pathological grade, showed excellent discrimination, with C-index values of 0.969 (95% CI, 0.933-1) and 0.941 (95% CI, 0.868-1) in the primary and validation cohorts, respectively. The calibration curve showed a good agreement.Conclusions: The radiomics nomogram performed well for the preoperative prediction of PMI in patients with ECC and may be used as a supplementary tool to provide individualized treatment plans for patients with ECC.Key Points: • No previously reported study that has utilized radiomics nomogram to preoperatively predict PMI for patients with ECC. • Radiomics model involves radiomics features extracted from joint T2WI and DWI which characterize the heterogeneity between tumors in patients with ECC. • Radiomics nomogram can assist clinicians with individualized treatment decision-making for patients with ECC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop a radiomics nomogram by combining the optimized radiomics signatures extracted from 2D and/or 3D CT images and clinical predictors to assess the overall survival of patients with non-small cell lung cancer (NSCLC).Methods: One training cohort of 239 and two validation datasets of 80 and 52 NSCLC patients were enrolled in this study. Nine hundred seventy-five radiomics features were extracted from each patient's 2D and 3D CT images. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate a radiomics signature. Cox hazard survival analysis and Kaplan-Meier were performed in both cohorts. The radiomics nomogram was developed by integrating the optimized radiomics signature and clinical predictors, its calibration and discrimination were evaluated.Results: The radiomics signatures were significantly associated with NSCLC patients' survival time. The signature derived from the combined 2D and 3D features showed a better prognostic performance than those from 2D or 3D alone. Our radiomics nomogram integrated the optimal radiomics signature with clinical predictors showed a significant improvement in the prediction of patients' survival compared with clinical predictors alone in the validation cohort. The calibration curve showed predicted survival time was very close to the actual one.Conclusions: The radiomics signature from the combined 2D and 3D features further improved the predicted accuracy of survival prognosis for the patients with NSCLC. Combination of the optimal radiomics signature and clinical predictors performed better for individualied survival prognosis estimation in patients with NSCLC. These findings might affect trearment strategies and enable a step forward for precise medicine.Key Points: • We found both 2D and 3D radiomics signature have favorable prognosis, but 3D signature had a better performance. • The radiomics signature generated from the combined 2D and 3D features had a better predictive performance than those from 2D or 3D features. • Integrating the optimal radiomics signature with clinical predictors significantly improved the predictive power in patients' survival compared with clinical TNM staging alone. [ABSTRACT FROM AUTHOR]

It is difficult to accurately assess axillary lymph nodes metastasis and the diagnosis of axillary lymph nodes in patients with breast cancer is invasive and has low-sensitivity preoperatively. This study aims to develop a mammography-based radiomics nomogram for the preoperative prediction of ALN metastasis in patients with breast cancer. This study enrolled 147 patients with clinicopathologically confirmed breast cancer and preoperative mammography. Features were extracted from each patient's mammography images. The least absolute shrinkage and selection operator regression method was used to select features and build a signature in the primary cohort. The performance of the signature was assessed using support vector machines. We developed a nomogram by incorporating the signature with the clinicopathologic risk factors. The nomogram performance was estimated by its calibration ability in the primary and validation cohorts. The signature was consisted of 10 selected ALN-status-related features. The AUC of the signature from the primary cohort was 0.895 (95% CI, 0.887-0.909) and 0.875 (95% CI, 0.698-0.891) for the validation cohort. The C-Index of the nomogram from the primary cohort was 0.779 (95% CI, 0.752-0.793) and 0.809 (95% CI, 0.794-0.833) for the validation cohort. Our nomogram is a reliable and non-invasive tool for preoperative prediction of ALN status and can be used to optimize current treatment strategy for breast cancer patients. [ABSTRACT FROM AUTHOR]