The transcription factor MYB110 regulates plant height, lodging resistance, and grain yield in rice.

The high-yielding Green Revolution varieties of cereal crops are characterized by a semidwarf architecture and lodging resistance. Plant height is tightly regulated by the availability of phosphate (Pi), yet the underlying mechanism remains obscure. Here, we report that rice (Oryza sativa) R2R3-type Myeloblastosis (MYB) transcription factor MYB110 is a Pi-dependent negative regulator of plant height. MYB110 is a direct target of PHOSPHATE STARVATION RESPONSE 2 (OsPHR2) and regulates OsPHR2-mediated inhibition of rice height. Inactivation of MYB110 increased culm diameter and bending resistance, leading to enhanced lodging resistance despite increased plant height. Strikingly, the grain yield of myb110 mutants was elevated under both high- and low-Pi regimes. Two divergent haplotypes based on single nucleotide polymorphisms in the putative promoter of MYB110 corresponded with its transcript levels and plant height in response to Pi availability. Thus, fine-tuning MYB110 expression may be a potent strategy for further increasing the yield of Green Revolution cereal crop varieties.

A phased genome based on single sperm sequencing reveals crossover pattern and complex relatedness in tea plants.

For diploid organisms that are highly heterozygous, a phased haploid genome can greatly aid in functional genomic, population genetic and breeding studies. Based on the genome sequencing of 135 single sperm cells of the elite tea cultivar 'Fudingdabai', we herein phased the genome of Camellia sinensis, one of the most popular beverage crops worldwide. High-resolution genetic and recombination maps of Fudingdabai were constructed, which revealed that crossover (CO) positions were frequently located in the 5' and 3' ends of annotated genes, while CO distributions across the genome were random. The low CO frequency in tea can be explained by strong CO interference, and CO simulation revealed the proportion of interference insensitive CO ranged from 5.2% to 11.7%. We furthermore developed a method to infer the relatedness between tea accessions and detected complex kinship and genetic signatures of 106 tea accessions. Among them, 59 accessions were closely related with Fudingdabai and 31 of them were first-degree relatives. We additionally identified genes displaying allele specific expression patterns between the two haplotypes of Fudingdabai and genes displaying significantly differential expression levels between Fudingdabai and other haplotypes. These results lay the foundation for further investigation of genetic and epigenetic factors underpinning the regulation of gene expression and provide insights into the evolution of tea plants as well as a valuable genetic resource for future breeding efforts.

A novel rice grain size gene OsSNB was identified by genome-wide association study in natural population.

Increasing agricultural productivity is one of the most important goals of plant science research and imperative to meet the needs of a rapidly growing population. Rice (Oryza sativa L.) is one of the most important staple crops worldwide. Grain size is both a major determinant of grain yield in rice and a target trait for domestication and artificial breeding. Here, a genome-wide association study of grain length and grain width was performed using 996,722 SNP markers in 270 rice accessions. Five and four quantitative trait loci were identified for grain length and grain width, respectively. In particular, the novel grain size gene OsSNB was identified from qGW7, and further results showed that OsSNB negatively regulated grain size. Most notably, knockout mutant plants by CRISPR/Cas9 technology showed increased grain length, width, and weight, while overexpression of OsSNB yielded the opposite. Sequencing of this gene from the promoter to the 3'-untranslated region in 168 rice accessions from a wide geographic range identified eight haplotypes. Furthermore, Hap 3 has the highest grain width discovered in japonica subspecies. Compared to other haplotypes, Hap 3 has a 225 bp insertion in the promoter. Based on the difference between Hap 3 and other haplotypes, OsSNB_Indel2 was designed as a functional marker for the improvement of rice grain width. This could be directly used to assist selection toward an improvement of grain width. These findings suggest OsSNB as useful for further improvements in yield characteristics in most cultivars.

Genome-wide Association Study (GWAS) of mesocotyl elongation based on re-sequencing approach in rice.

BACKGROUND: Mechanized dry seeded rice can save both labour and water resources. Rice seedling establishment is sensitive to sowing depth while mesocotyl elongation facilitates the emergence of deeply sown seeds. RESULTS: A set of 270 rice accessions, including 170 from the mini-core collection of Chinese rice germplasm (C Collection) and 100 varieties used in a breeding program for drought resistance (D Collection), was screened for mesocotyl lengths of seedlings grown in water (MLw) in darkness and in 5 cm sand culture (MLs). Twenty six accessions (10.53 %) have MLw longer than 1.0 cm. Eleven accessions had the highest mesocotyl lengths, i.e. 1.4 - 5.05 cm of MLw and 3.0 - 6.4 cm in 10 cm sand culture, including 7 upland landraces or varieties. The genotypic data of 1,019,883 SNPs were developed by re-sequencing of those accessions. A whole-genome SNP array (Rice SNP50) was used to genotype 24 accessions as a validation panel, giving 98.41 % of consistent SNPs with the re-sequencing data in average. GWAS based on compressed mixed linear model was conducted using GAPIT. Based on a threshold of -log(P) ≥8.0, 13 loci were associated to MLw on rice chromosome 1, 3, 4, 5, 6 and 9, respectively. Three associated loci, on chromosome 3, 6, and 10, were detected for MLs. A set of 99 associated SNPs for MLw, based on a compromised threshold (-log(P) ≥7.0), located in intergenic regions or different positions of 36 annotated genes, including one cullin and one growth regulating factor gene. CONCLUSIONS: Higher proportion and extension of elongated mesocotyls were observed in the mini-core collection of rice germplasm and upland rice landraces or varieties, possibly causing the correlation between mesocotyl elongation and drought resistance. GWAS found 13 loci for mesocotyl length measured in dark germination that confirmed the previously reported co-location of two QTLs across populations and experiments. Associated SNPs hit 36 annotated genes including function-matching candidates like cullin and GRF. The germplasm with elongated mesocotyl, especially upland landraces or varieties, and the associated SNPs could be useful in further studies and breeding of mechanized dry seeded rice.

Quantitative trait locus mapping of deep rooting by linkage and association analysis in rice.

Deep rooting is a very important trait for plants' drought avoidance, and it is usually represented by the ratio of deep rooting (RDR). Three sets of rice populations were used to determine the genetic base for RDR. A linkage mapping population with 180 recombinant inbred lines and an association mapping population containing 237 rice varieties were used to identify genes linked to RDR. Six quantitative trait loci (QTLs) of RDR were identified as being located on chromosomes 1, 2, 4, 7, and 10. Using 1 019 883 single-nucleotide polymorphisms (SNPs), a genome-wide association study of the RDR was performed. Forty-eight significant SNPs of the RDR were identified and formed a clear peak on the short arm of chromosome 1 in a Manhattan plot. Compared with the shallow-rooting group and the whole collection, the deep-rooting group had selective sweep regions on chromosomes 1 and 2, especially in the major QTL region on chromosome 2. Seven of the nine candidate SNPs identified by association mapping were verified in two RDR extreme groups. The findings from this study will be beneficial to rice drought-resistance research and breeding.

Dissection of additive, epistatic effect and QTL × environment interaction of quantitative trait loci for sheath blight resistance in rice.

A recombinant inbred line (RIL) population from a cross between 'HH1B' and 'RSB02' (a deep-water rice variety with resistance to sheath blight) was planted in two locations for four different growing seasons. Seven traits were used to evaluate the disease severity, namely disease rating (DR), lesion length (LL), lesion height (LH), relative lesion length (RLL), relative lesion height (RLH), plant height (PH) and heading date (HD). Based on a linkage map of 163 simple sequence repeat (SSR) markers, a total of 37 QTLs were mapped on nine chromosomes. Additionally, 32 epistatic QTLs were identified, distributed on all the 12 chromosomes. The contribution of a single QTL's additive and epistatic effect was of low magnitude for most cases (from 0.39% to 24.62%). Among QTL × environment interaction test, 28 additive QTLs and six pairs of epistatic interactions were involved. Correlation analysis showed that DR had significant positive correlations with LL, RLL and RLH, but had a negative correlation with PH, two of six QTLs controlling DR were mapped in the same chromosome regions as the QTLs controlling PH. The alleles which can enhance disease resistance and increase PH are from the resistant parent 'RSB02', indicating that PH has certain effect on sheath blight resistance in the present study.

EPYC functions as a novel prognostic biomarker for pancreatic cancer.

Pancreatic cancer (PC) has become a worldwide challenge attributed to its difficult early diagnosis and rapid progression. Treatments continue to be limited besides surgical resection. Hence, we aimed to discover novel biological signatures as clinically effective therapeutic targets for PC via the mining of public tumor databases. We found that epiphycan (EPYC) could function as an independent risk factor to predict the poor prognosis in PC based on integrated bioinformatics analysis. We downloaded associated PC data profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) online websites, then applied the software Rstudio to filter out genes under the strict criteria. After the batch survival analysis using Log-rank test and univariate cox regression, we obtained 39 candidate genes. Subsequently, we narrowed the scope to 8 genes by establishing a Lasso regression model. Eventually, we focused on 2 genes (EPYC and MET) by further building a multivariate cox regression model. Given that the role of EPYC in PC remains obscure, we then performed a series of molecular functional experiments, including RT-qPCR, CCK8, EdU, colony formation, Transwell, western blot, cell live-dead staining, subcutaneous tumor formation, to enhance our insight into its underlying molecular mechanisms. The above results demonstrated that EPYC was highly expressed in PC cell lines and could promote the proliferation of PCs via PI3K-AKT signaling pathway in vivo and in vitro. We arrived at a conclusion that EPYC was expected to be a biological neo-biomarker for PC followed by being a potential therapeutic target.

The METTL3/miR-196a Axis Predicts Poor Prognosis in Non-small Cell Lung Cancer.

Background: METTL3 accelerates m6A modification to influence cancer progression including non-small cell lung cancer (NSCLC). To illustrate the role and underlying mechanism of METTL3 mediated miR-196a upregulation in NSCLC. Method: The global level of m6A modification was detected by qPCR, western blot and immumohistochemical staining. The TCGA, GEPIA, CPTAC and TIMER databases were used to explore the expression change of METTL3, miR-196a and GAS7 in NSCLC patients. Kaplan-Meier analysis was performed to analyze the prognostic value of miR-196a. NSCLC cells overexpressed or knockdown miR-196a were constructed and used for CCK8, colony formation assay, western blot and immunofluorescence in vitro. The effect of miR-196a on tumor growth was investigated in vivo. Result: We found that METTL3 mediated miR-196a were notably enhancive in NSCLC tissues and in NSCLC cells, which is markedly positively related with the serious TNM stage, the large tumor size, the distant metastasis, and the poor prognosis in patients of NSCLC. Further investigation showed that up-regulated miR-196a promoted cell viability and cell autophagy, while down-regulation of miR-196a revealed opposite results in H1299 and A549 cells. In terms of mechanism, we found that miR-196a interacted with GAS7. In addition, GAS7 expression in NSCLC patients may be positively related with the infiltration of immune cell subsets in tumor microenvironment (TME). Conclusion: The axis of METTL3-miR-196a-GAS7 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for NSCLC patients.

Pathophysiological consequences and treatment strategy of obstructive jaundice.

Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

Genome-wide association study identifies a gene conferring high physiological phosphorus use efficiency in rice.

Phosphate (Pi) is indispensable for the growth and development of plant, and low-Pi stress is a major limitation for crop growth and yield worldwide. The tolerance to low-Pi stress varied among rice germplasm resources. However, the mechanisms underlying the tolerance of rice to low-Pi stress, as a complex quantitative trait, are not clear. We performed a genome-wide association study (GWAS) through a diverse worldwide collection of 191 rice accessions in the field under normal-Pi and low-Pi supply in two years. Twenty and three significant association loci were identified for biomass and grain yield per plant under low-Pi supply respectively. The expression level of OsAAD as a candidate gene from a associated locus was significantly up-regulated after low-Pi stress treatment for five days and tended to return to normal levels after Pi re-supply in shoots. Suppression of OsAAD expression could improve the physiological phosphorus use efficiency (PPUE) and grain yields through affecting the expression of several genes associated with GA biosynthesis and metabolism. OsAAD would be a promising gene for increasing PPUE and grain yield in rice under normal- and low-Pi supply via genome editing.

The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy.

Traditional Chinese medicine has been used in China for thousands of years. In 2022, the 14th Five-Year Plan for the Development of Traditional Chinese Medicine was released, aiming to enhance traditional Chinese medicine health services and improve policies and systems for high-quality traditional Chinese medicinal development by 2025. ERIANIN, the main component of the traditional Chinese medicine Dendrobium, plays an important role in anti-inflammatory, antiviral, antitumor, antiangiogenic, and other pharmacological effects. ERIANIN has broad-spectrum antitumor effects, and its tumor-suppressive effects have been confirmed in the study of various diseases, such as precancerous lesions of the stomach, gastric cancer, liver cancer, lung cancer, prostate cancer, bladder cancer, breast cancer, cervical cancer, osteosarcoma, colorectal cancer, leukaemia, nasopharyngeal cancer and melanoma through the multiple signaling pathways. Thus, the aim of this review was to systematically summarise the research on ERIANIN with the aim of serving as a reference for future research on this compound and briefly discuss some future perspectives development of ERIANIN in combined immunotherapy.

Lobar or sublobar resection for early-stage second primary lung cancer ≤ 3 cm in size: a SEER population-based study.

PURPOSE: Surgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice. METHODS: A retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups. RESULTS: A total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2-3 cm (P < 0.05). CONCLUSION: The OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2-3 cm tumor size, lobar resection is more advantageous than sublobar resection.

Identification of Genetic Loci for Rice Seedling Mesocotyl Elongation in Both Natural and Artificial Segregating Populations.

Mesocotyl elongation of rice seedlings is a key trait for deep sowing tolerance and well seedling establishment in dry direct sowing rice (DDSR) production. Subsets of the Rice Diversity Panel 1 (RDP1, 294 accessions) and Hanyou 73 (HY73) recombinant inbred line (RIL) population (312 lines) were screened for mesocotyl length (ML) via dark germination. Six RDP1 accessions (Phudugey, Kasalath, CA902B21, Surjamkuhi, Djimoron, and Goria) had an ML longer than 10 cm, with the other 19 accessions being over 4 cm. A GWAS in RDP1 detected 118 associated SNPs on all 12 chromosomes using a threshold of FDR-adjusted p < 0.05, including 11 SNPs on chromosomes 1, 4, 5, 7, 10, and 12 declared by -log10(P) > 5.868 as the Bonferroni-corrected threshold. Using phenotypic data of three successive trials and a high-density bin map from resequencing genotypic data, four to six QTLs were detected on chromosomes 1, 2, 5, 6, and 10, including three loci repeatedly mapped for ML from two or three replicated trials. Candidate genes were predicted from the chromosomal regions covered by the associated LD blocks and the confidence intervals (CIs) of QTLs and partially validated by the dynamic RNA-seq data in the mesocotyl along different periods of light exposure. Potential strategies of donor parent selection for seedling establishment in DDSR breeding were discussed.

Genetic, proteomic and metabolic analysis of the regulation of energy storage in rice seedlings in response to drought.

We used proteomic analysis to determine the response of rice plant seedlings to drought-induced stress. The expression of 71 protein spots was significantly altered, and 60 spots were successfully identified. The greatest down-regulated protein functional category was translation. Up-regulated proteins were mainly related to protein folding and assembly. Additionally, many proteins involved in metabolism (e.g. carbohydrate metabolism) also showed differences in expression. cDNA microarray and GC-MS analysis showed 4756 differentially expressed mRNAs and 37 differentially expressed metabolites. Once these data were integrated with the proteomic analysis, we were able to elucidate the metabolic pathways affected by drought-induced stress. These results suggest that increased energy consumption from storage substances occurred during drought. In addition, increased expression of the enzymes involved in anabolic pathways corresponded with an increase in the content of six amino acids. We speculated that energy conversion from carbohydrates and/or fatty acids to amino acids was increased. Analysis of basic metabolism networks allowed us to understand how rice plants adjust to drought conditions.

Proteomic analysis of rice leaves shows the different regulations to osmotic stress and stress signals.

Following the idea of partial root-zone drying (PRD) in crop cultivation, the morphological and physiological responses to partial root osmotic stress (PROS) and whole root osmotic stress (WROS) were investigated in rice. WROS caused stress symptoms like leaf rolling and membrane leakage. PROS stimulated stress signals, but did not cause severe leaf damage. By proteomic analysis, a total of 58 proteins showed differential expression after one or both treatments, and functional classification of these proteins suggests that stress signals regulate photosynthesis, carbohydrate and energy metabolism. Two other proteins (anthranilate synthase and submergence-induced nickel-binding protein) were upregulated only in the PROS plants, indicating their important roles in stress resistance. Additionally, more enzymes were involved in stress defense, redox homeostasis, lignin and ethylene synthesis in WROS leaves, suggesting a more comprehensive regulatory mechanism induced by osmotic stress. This study provides new insights into the complex molecular networks within plant leaves involved in the adaptation to osmotic stress and stress signals.

Population structure and association mapping on chromosome 7 using a diverse panel of Chinese germplasm of rice (Oryza sativa L.).

The majority of 170 rice accessions used in this study were diverse landraces or varieties from a putative mini-core collection of Chinese germplasm along with some widely used parental lines in genetic analysis or breeding (a few from abroad). The population was genotyped using 84 SSR or InDel markers on chromosome 7 and 48 markers on other chromosomes. The phenotyping of heading date, plant height and panicle length were carried out in different locations for 2 years. Based on morphological characterization, distance-based clustering and model-based estimation of marker data, the population showed a predominant structure with two subpopulations in correspondence with indica and japonica subspecies. The estimation of linkage disequilibrium in 2 Mb windows varied along chromosome 7 and showed parallel changes with inter-subspecies differentiation of marker loci (Fst). Based on the mixed linear model considering population structure and family relatedness [i.e. the (Q + K) model], one to three associated markers (P < or = 0.0001) per trait per experiment were scanned out on rice chromosome 7. Most significant loci were repeated for the data from both field experiments while two loci were associated with two or three traits. Marker-based allelic effects were shown in a couple of associated markers as examples. The application of association results in breeding program was also discussed.

Dynamic transcriptome and phytohormone profiling along the time of light exposure in the mesocotyl of rice seedling.

Mesocotyl elongation is an important trait influencing seedling emergence and establishment in rice direct-seeding cultivation and is immediately inhibited after light exposure. Detailed researches on the molecular basis and biological processes underlying light repression of mesocotyl growth could probably provide useful information for key factors controlling this trait. Here we monitored the transcriptome and endogenous phytohormone changes specifically in the elongating mesocotyl in response to light exposure with a time-course. It was revealed that 974 transcripts were significantly differentially expressed (FDR < 0.05, |log2 (L/D) | ≥2) after light exposure. Most of the differential expression genes associated with the responses to hormone. Metabolic pathway analysis using the KEGG system suggested plant hormone signal transduction, α-linolenic acid metabolism and diterpenoid biosynthesis were critical processes of mesocotyl growth inhibited by light. Consistent with DEGs, the endogenous IAA, tZ and GA3 content was significantly reduced while JA level was dramatically increased, which indicated that light inhibited rice mesocotyl growth through decreasing IAA, tZ and GA3 content and/or increasing JA level. The present results enriched our knowledge about the genes and phytohormones regulating mesocotyl elongation in rice, which may help improve future studies on associated genes and develop new varieties tolerance to deep sowing.

Comparative Analysis of Expression Profiles of Panicle Development among Tolerant and Sensitive Rice in Response to Drought Stress.

Water deficit caused a serious threat to crops, especially panicle development at reproductive growth phase. We investigated grain yield components and gene expression profiles of panicle among tolerant and sensitive rice in response to drought stress. Panicle morphologies exhibited that secondary branches per panicle were more severely affected as compared to primary branches per panicle. Moreover, grain weight per panicle showed significant decrease for both tolerant and sensitive varieties except for MILT1444. Expression profile analysis revealed that 783 differentially expressed genes (DEGs) were identified to be drought-induced from young panicles in 2 cm length. Hierarchical clustering indicated that 76.8% of DEGs were up-regulated for all six rice varieties, and the percentage of down-regulated genes was higher in sensitive group than tolerant group. Biological process category revealed that the shared Gene Ontology (GO) terms were involved in response to abiotic stimulus and stress, whereas the specific GO terms in tolerant group were identified as regulation of biological quality, homeostatic process, cell growth, anatomical structure morphogenesis and development, and the unique terms in sensitive varieties were identified as lipid metabolic process and secondary metabolic process. Furthermore, the gene-based association analysis narrowed down list of DEGs, and four genes common to all six varieties were selected as candidate for breeders. Together, we found several shared and distinct biological processes between tolerant and sensitive varieties, and candidate stress-responsive genes. These findings provided insight into functional mechanisms regulating drought stress response in panicle development and may also help to crop tolerant improvement.

Root Transcriptomic Analysis Revealing the Importance of Energy Metabolism to the Development of Deep Roots in Rice (Oryza sativa L.).

Drought is the most serious abiotic stress limiting rice production, and deep root is the key contributor to drought avoidance. However, the genetic mechanism regulating the development of deep roots is largely unknown. In this study, the transcriptomes of 74 root samples from 37 rice varieties, representing the extreme genotypes of shallow or deep rooting, were surveyed by RNA-seq. The 13,242 differentially expressed genes (DEGs) between deep rooting and shallow rooting varieties (H vs. L) were enriched in the pathway of genetic information processing and metabolism, while the 1,052 DEGs between the deep roots and shallow roots from each of the plants (D vs. S) were significantly enriched in metabolic pathways especially energy metabolism. Ten quantitative trait transcripts (QTTs) were identified and some were involved in energy metabolism. Forty-nine candidate DEGs were confirmed by qRT-PCR and microarray. Through weighted gene co-expression network analysis (WGCNA), we found 18 hub genes. Surprisingly, all these hub genes expressed higher in deep roots than in shallow roots, furthermore half of them functioned in energy metabolism. We also estimated that the ATP production in the deep roots was faster than shallow roots. Our results provided a lot of reliable candidate genes to improve deep rooting, and firstly highlight the importance of energy metabolism to the development of deep roots.