Toward understanding and utilizing crop heterosis in the age of biotechnology.

Heterosis, a universal phenomenon in nature, mainly reflected in the superior productivity, quality, and fitness of F1 hybrids compared with their inbred parents, has been exploited in agriculture and greatly benefited human society in terms of food security. However, the flexible and efficient utilization of heterosis has remained a challenge in hybrid breeding systems because of the limitations of "three-line" and "two-line" methods. In the past two decades, rapidly developed biotechnologies have provided unprecedented conveniences for both understanding and utilizing heterosis. Notably, "third-generation" (3G) hybrid breeding technology together with high-throughput sequencing and gene editing greatly promoted the efficiency of hybrid breeding. Here, we review emerging ideas about the genetic or molecular mechanisms of heterosis and the development of 3G hybrid breeding system in the age of biotechnology. In addition, we summarized opportunities and challenges for optimal heterosis utilization in the future.

Increased long-distance and homo-trans interactions related to H3K27me3 in Arabidopsis hybrids.

In plants, the genome structure of hybrids changes compared with their parents, but the effects of these changes in hybrids remain elusive. Comparing reciprocal crosses between Col × C24 and C24 × Col in Arabidopsis using high-throughput chromosome conformation capture assay (Hi-C) analysis, we found that hybrid three-dimensional (3D) chromatin organization had more long-distance interactions relative to parents, and this was mainly located in promoter regions and enriched in genes with heterosis-related pathways. The interactions between euchromatin and heterochromatin were increased, and the compartment strength decreased in hybrids. In compartment domain (CD) boundaries, the distal interactions were more in hybrids than their parents. In the hybrids of CURLY LEAF (clf) mutants clfCol × clfC24 and clfC24 × clfCol , the heterosis phenotype was damaged, and the long-distance interactions in hybrids were fewer than in their parents with lower H3K27me3. ChIP-seq data revealed higher levels of H3K27me3 in the region adjacent to the CD boundary and the same interactional homo-trans sites in the wild-type (WT) hybrids, which may have led to more long-distance interactions. In addition, the differentially expressed genes (DEGs) located in the boundaries of CDs and loop regions changed obviously in WT, and the functional enrichment for DEGs was different between WT and clf in the long-distance interactions and loop regions. Our findings may therefore propose a new epigenetic explanation of heterosis in the Arabidopsis hybrids and provide new insights into crop breeding and yield increase.

CircMAPK1 promoted CD8 + T cell infiltration in LUAD by improving the IGF2BP1 dependent CCL5 upregulation.

Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer and has a poor prognosis. Immune Checkpoint Blockage (ICB) have been shown to improve the survival of LUAD in the last decade. CD8 + T cell infiltration is significantly related to LUAD prognosis and plays a critical role in ICB response efficiency. Chemokines expressed and secreted by tumor and microenvironment cells regulate the recruitment of CD8 + T cells. A cytoplasm-dominant circRNA, termed circMAPK1, was found to be down-regulated in LUAD and dramatically suppressed the growth of LUAD upon circMAPK1 overexpression in immunocompetent mice. Meanwhile, it was found that circMAPK1 significantly promoted the CD8 + T cell intratumoral infiltration in vitro and in vivo. CircMAPK1 was identified as binding IGF2BP1 in the cytoplasm and inducing IGF2BP1 to occupy the 3'UTR of CCL5 mRNA, resulting in retained stability of CCL5 mRNA. In general, circMAPK1 is a microenvironment-associated circRNA that recruits CD8 + T cells in LUAD. CircMAPK1 is an effective microenvironment regulator and a potential nucleic acid drug that can be combined with ICB to improve immunotherapy response efficiency.

Genetic and molecular regulation of increased photosynthetic cell number contributes to leaf size heterosis in Arabidopsis.

Heterosis is an important genetic phenomenon that has been observed and widely utilized in agriculture. However, the genetic and molecular bases of heterosis are unclear. Through transcriptome-wide association studies (TWAS) and expression quantitative trait locus (eQTL) analysis to integrate genome, transcriptome, and heterotic phenotype of a half-sibling Arabidopsis hybrid population, we report that the genetic and molecular bases of variations in leaf growth heterosis can be explained by the varied expression levels of growth-regulating genes resulting from distinct sets of heterozygous eQTLs carried by the half-sibling hybrids. In F1 versus parent, the degree of up-regulated gene expression in the cell cycle pathway in the shoot apex and the photosynthesis pathway in true leaf positively correlates with true leaf area heterosis level, and this is affected by the accumulation of superior heterozygous eQTLs. This was further corroborated by the major contribution of increased photosynthetic cell number to leaf area heterosis.

Dynamic contrast-enhanced CT and clinical features of sarcomatoid hepatocellular carcinoma.

PURPOSE: To investigate the dynamic contrast-enhanced computed tomography (CECT) features and clinical characteristics of sarcomatoid hepatocellular carcinoma (S-HCC). METHODS: We retrospectively reviewed the CECT data and clinical findings of 13 patients (11 male and 2 female, with an average age of 58.6 ± 11.2 years) with pathologically proven S-HCC, including 9 patients with surgical resection and 4 patients with biopsy examination. All patients underwent CECT scans. Two radiologists reviewed and evaluated general features, CECT features and extratumoral features of each lesions based on a consensus. RESULTS: Among the thirteen tumors, a mean size of 66.7 mm was observed, ranging in diameter from 30 to 146 mm. Seven of thirteen patients had hepatitis B virus (HBV) infection and an elevation of alpha-fetoprotein (AFP) level. Most of cases located in the right lobe of liver (84.6%, 11/13). Nine of thirteen tumors showed lobulated or wavy contours and infiltrative morphology, while eight tumors presented with unclear margin. The tumor textures were mainly heterogeneous for ischemia or necrosis, with solid components dominantly in all cases. Eight of thirteen tumors exhibited "slow-in and and slow-out" dynamic enhancement pattern in CECT, with a enhancement peak in the portal venous phase. Portal vein or hepatic thrombus, adjacent organs invasion and lymph node metastasis were observed in two patients, respectively. Four of thirteen lesions occurred intrahepatic metastasis and hepatic surface retraction respectively. CONCLUSION: S-HCC gengerally seen in elderly male with HBV infection and elevated AFP level. The CT manifestations including: large diameter, frequently hepatic right lobe involvement, lobular or wavy contours, ill-defined margins, infiltrative morphology, obvious heterogeneity and dynamic enhancement pattern of "slow-in and and slow-out" , contributed to the diagnosis of S-HCC. These tumors usually occurred hepatic surface retraction and intrahepatic metastasis.

Serum vitamin C levels and risk of non-alcoholic fatty liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Background and aims: Vitamin C, as an antioxidant, may play a role in the treatment of NAFLD. This research aimed to investigate the association of serum vitamin C levels with the risk of NAFLD and to further examine the causal relationship by Mendelian randomization (MR) method. Methods: The cross-sectional study selected 5,578 participants of the National Health and Nutrition Examination Survey (NHANES), 2005-2006 and 2017-2018. The association of serum vitamin C levels with NAFLD risk was evaluated under a multivariable logistic regression model. A two-sample MR study, using genetic data from large-scale genome-wide association studies (GWAS) of serum vitamin C levels (52,014 individuals) and NAFLD (primary analysis: 1,483 cases /17,781 controls; secondary analysis: 1,908 cases/340,591 controls), was conducted to infer causality between them. The inverse-variance-weighted (IVW) was applied as the main method of MR analysis. A series of sensitivity analyzes were used to evaluate the pleiotropy. Results: In the cross-sectional study, results showed that Tertile 3 group (Tertile 3: ≥1.06 mg/dl) had a significantly lower risk (OR = 0.59, 95% CI: 0.48 ~ 0.74, p < 0.001) of NAFLD than Tertile 1 group (Tertile 1: ≤0.69 mg/dl) after full adjustments. In regard to gender, serum vitamin C was protective against NAFLD in both women (OR = 0.63, 95% CI: 0.49 ~ 0.80, p < 0.001) and men (OR = 0.73, 95% CI: 0.55 ~ 0.97, p = 0.029) but was stronger among women. However, in the IVW of MR analyzes, no causal relationship between serum vitamin C levels and NAFLD risk was observed in the primary analysis (OR = 0.82, 95% CI: 0.47 ~ 1.45, p = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53 ~ 1.22, p = 0.308). MR sensitivity analyzes yielded consistent results. Conclusion: Our MR study did not support a causal association between serum vitamin C levels and NAFLD risk. Further studies with greater cases are warranted to confirm our findings.

The B-Type Cyclin CYCB1-1 Regulates Embryonic Development and Seed Size in Maize.

Progress through the cell cycle is a critical process during plant embryo and seed development and its progression is regulated by cyclins. Despite extensive study of cyclins in other systems, their role in embryo and seed development of maize is unclear. In this study, we demonstrate that ZmCYCB1-1 overexpression significantly accelerated embryo growth and increased seed size. In situ hybridization and toluidine blue staining indicated that ZmCYCB1-1 was highly expressed in the plumule of embryos, and the cells of the plumule were smaller, denser, and more regularly arranged in ZmCYCB1-1 overexpression plants. Overexpression of ZmCYCB1-1 in maize also resulted in an increased ear length and enhanced kernel weight by increasing kernel width. Transcriptome analysis indicated that the overexpression of ZmCYCB1-1 affected several different metabolic pathways, including photosynthesis in embryos and leaves, and lipid metabolism in leaves. Conversely, knocking out ZmCYCB1-1 resulted in plants with slow growth. Our results suggest that ZmCYCB1-1 regulates embryo growth and seed size, making it an ideal target for efforts aimed at maize yield improvement.

Natural variation in the transcription factor REPLUMLESS contributes to both disease resistance and plant growth in Arabidopsis.

When attacked by pathogens, plants need to reallocate energy from growth to defense to fend off the invaders, frequently incurring growth penalties. This phenomenon is known as the growth-defense tradeoff and is orchestrated by a hardwired transcriptional network. Altering key factors involved in this network has the potential to increase disease resistance without growth or yield loss, but the mechanisms underlying such changes require further investigation. By conducting a genome-wide association study (GWAS) of leaves infected by the hemi-biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000, we discovered that the Arabidopsis transcription factor REPLUMLESS (RPL) is necessary for bacterial resistance. More importantly, RPL functions in promoting both disease resistance and growth. Transcriptome analysis revealed a cluster of genes in the GRETCHEN HAGEN 3 (GH3) family that were significantly upregulated in rpl mutants, leading to the accumulation of indole-3-acetic acid-aspartic acid (IAA-Asp). Consistent with this observation, transcripts of virulence effector genes were activated by IAA-Asp accumulated in the rpl mutants. We found that RPL protein could directly bind to GH3 promoters and repress their expression. RPL also repressed flavonol synthesis by directly repressing CHI expression and thus activated the auxin transport pathway, which promotes plant growth. Therefore, RPL plays an important role in plant immunity and functions in the auxin pathway to optimize Arabidopsis growth and defense.

Fudosteine attenuates acute lung injury in septic mice by inhibiting pyroptosis via the TXNIP/NLRP3/GSDMD pathway.

There is a dearth of effective pharmacotherapies for sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to which oxidative stress and excessive inflammation are major contributors. We hypothesized that fudosteine, a cysteine derivative, may protect against sepsis-induced ALI/ARDS given its anti-oxidant capacity. This study aimed to investigate the effects and mechanisms of fudosteine in a mouse model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP). The intragastrical administration of fudosteine (25 mg/kg, 50 mg/kg, and 100 mg/kg) dose-dependently decreased proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and serum and reduced BALF/serum albumin and lung wet/dry weight ratios in septic mice. The lung injury score was significantly lowered by fudosteine [e.g., 0.18 ± 0.03 (100 mg/kg) vs. 0.42 ± 0.03 (CLP), P < 0.0001]. Fudosteine also reduced the biomarkers of lung epithelial injury in BALF and markedly improved oxidative stress indicators in lung tissues [e.g., malondialdehyde: 337.70 ± 23.78 (100 mg/kg) vs. 686.40 ± 28.36 (CLP) nmol/mg protein, P < 0.0001]. Lung tissue transcriptomics analyses revealed suppressed inflammatory responses and oxidative stress with fudosteine and the involvement of the inflammasome and pyroptosis pathways. Western blot analyses indicated that fudosteine inhibited the sepsis-induced activation of gasdermin D (GSDMD) and caspase-1 and the upregulation of thioredoxin-interacting protein (TXNIP), nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3), and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Fudosteine therefore protects against sepsis-induced ALI in mice, and the inhibition of pyroptosis via the TXNIP/NLRP3/GSDMD pathway may be an underlying mechanism.

From hybrid genomes to heterotic trait output: Challenges and opportunities.

Heterosis (or hybrid vigor) has been widely used in crop seed breeding to improve many key economic traits. Nevertheless, the genetic and molecular basis of this important phenomenon has long remained elusive, constraining its flexible and effective exploitation. Advanced genomic approaches are efficient in characterizing the mechanism of heterosis. Here, we review how the omics approaches, including genomic, transcriptomic, and population genetics methods such as genome-wide association studies, can reveal how hybrid genomes outperform parental genomes in plants. This information opens up opportunities for genomic exploration and manipulation of heterosis in crop breeding.

Effect of family enteral nutrition on nutritional status in elderly patients with esophageal carcinoma after minimally invasive radical surgery: a randomized trial.

BACKGROUND: Postoperative patients with esophageal carcinoma (EC) are prone to malnutrition. Studies have shown that the incidence of malnutrition after EC surgery reaches 60-80%, and deaths due to malnutrition account for about 22%. Patients with EC need at least 3 months to establish a new dietary pattern after surgery, so short-term enteral nutrition is of great significance. The aim of the present study was to investigate the effects of family enteral nutrition (FEN) on nutritional status in elderly patients with EC after minimally invasive radical surgery (MIS). METHODS: A total of 106 elderly patients with EC, who had undergone MIS at the 904th Hospital of the Joint Service Support Center of the Chinese People's Liberation Army and Taixing People's Hospital from January 2017 to July 2019 were selected to participate in the present study and randomly divided into the observation group and control group. There were 53 cases in each group. Patients in the control group were given regular meals after they were discharged from hospital, and the observation group was given FEN support based on the intervention of the control group. Body mass index (BMI), nutritional risk screening, nutritional status, and the incidence of complications were compared between the two groups at discharge and 1 month after discharge. RESULTS: The BMI of the observation group was higher than that of the control group 1 month after discharge (P<0.05). The nutritional risk ratio of the observation group was lower than that of the control group 1 month after discharge (P<0.05). Hemoglobin, serum albumin, serum total protein, transferrin, and serum prealbumin of the observation group were higher than the control group 1 month after discharge (P<0.05). There was no significant difference in the incidence of total complications between the two groups (P>0.05). CONCLUSIONS: FEN could improve the nutritional status of elderly patients with EC after MIS and reduce the risk of postoperative malnutrition and incidence of complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046121.

A central circadian oscillator confers defense heterosis in hybrids without growth vigor costs.

Plant immunity frequently incurs growth penalties, which known as the trade-off between immunity and growth. Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits but rarely for disease resistance. Here, we report that the central circadian oscillator, CCA1, confers heterosis for bacterial defense in hybrids without growth vigor costs, and it even significantly enhances the growth heterosis of hybrids under pathogen infection. The genetic perturbation of CCA1 abrogated heterosis for both defense and growth in hybrids. Upon pathogen attack, the expression of CCA1 in F1 hybrids is precisely modulated at different time points during the day by its rhythmic histone modifications. Before dawn of the first infection day, epigenetic activation of CCA1 promotes an elevation of salicylic acid accumulation in hybrids, enabling heterosis for defense. During the middle of every infection day, diurnal epigenetic repression of CCA1 leads to rhythmically increased chlorophyll synthesis and starch metabolism in hybrids, effectively eliminating the immunity-growth heterosis trade-offs in hybrids.

Biological pathway expression complementation contributes to biomass heterosis in Arabidopsis.

The mechanisms underlying heterosis have long remained a matter of debate, despite its agricultural importance. How changes in transcriptional networks during plant development are relevant to the continuous manifestation of growth vigor in hybrids is intriguing and unexplored. Here, we present an integrated high-resolution analysis of the daily dynamic growth phenotypes and transcriptome atlases of young Arabidopsis seedlings (parental ecotypes [Col-0 and Per-1] and their F1 hybrid). Weighted gene coexpression network analysis uncovered divergent expression patterns between parents of the network hub genes, in which genes related to the cell cycle were more highly expressed in one parent (Col-0), whereas those involved in photosynthesis were more highly expressed in the other parent (Per-1). Notably, the hybrid exhibited spatiotemporal high-parent-dominant expression complementation of network hub genes in the two pathways during seedling growth. This suggests that the integrated capacities of cell division and photosynthesis contribute to hybrid growth vigor, which could be enhanced by temporal advances in the progression of leaf development in the hybrid relative to its parents. Altogether, this study provides evidence of expression complementation between fundamental biological pathways in hybrids and highlights the contribution of expression dominance in heterosis.

Insertion trauma of a new cochlear implant electrode: evaluated by histology in fresh human temporal bone specimens.

BACKGROUND: Combining acoustic and electrical stimulation has been successfully used in patients with low-frequency residual hearing. Electrode insertion trauma, such as electrode translocation could result in loss of residual hearing. OBJECTIVES: The aim of the study is to evaluate the LCI-20PI electrode array insertion trauma to the intra-cochlear structures in fresh human temporal bone specimens. MATERIALS AND METHODS: The LCI-20PI electrode arrays were inserted into scalae tympani through round window membrane in 10 cochleae from ten fresh human cadavers. The intracochlear trauma was evaluated histologically by a scale of 0-4: 0 - no observable trauma, 1 - elevation of basilar membrane, 2 - rupture of basilar membrane or spiral ligament, 3-dislocation into scala vestibuli and 4 - fracture of modiolus or osseous spiral lamina. The insertion depth was measured by radiography. RESULTS: Histological results revealed no observable trauma in seven specimens; basal membrane elevation and rupture in two specimens; the electrode array misled into scala vestibuli in one specimen. The insertion depth varied from 228° to 288°. CONCLUSIONS AND SIGNIFICANCE: The insertion of the LCI-20PI electrode arrays caused no trauma in the majority of the fresh temporal bone specimens. No translocation of the electrode arrays from the scala tympani to the scala vestibuli was observed.

[Resveratrol inhibits hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells through the HIF-1α/NOX4/ROS signaling pathway].

The purpose of the present study was to determine the effects of resveratrol on hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism. Primary rat PASMCs were isolated and cultured in vitro and pretreated with different concentrations of resveratrol (10, 20, and 40 µmol/L) or the NADPH oxidase (NOX) inhibitor VAS2870 (10 µmol/L) for 0.5 h. The cells were then cultured under normoxia (21% O2, 5% CO2) or hypoxia (2% O2, 5% CO2) for 24 h. The proliferation of cells was measured using the CCK-8 method and the expression of proliferating cell nuclear antigen (PCNA). The production of reactive oxygen species (ROS) was detected by DCFH-DA. The expression of rat NOX1, NOX4 and hypoxia inducible factor 1α (HIF-1α) was detected by real-time RT-PCR and Western blotting assays. The related signaling pathways were determined using the small interference RNAs (siRNAs) specifically targeting Hif-1α and Nox4. The results showed that resveratrol and VAS2870 significantly inhibited hypoxia-induced cell proliferation and ROS production in rat PASMCs. Resveratrol also effectively prevented hypoxia-induced increase of HIF-1α protein levels and NOX4 up-regulation, but had little effect on NOX1. After the knocking down of Hif-1α or Nox4 with siRNAs, hypoxia-induced cell proliferation and ROS accumulation were significantly decreased, and both were further inhibited by resveratrol treatment. These results suggest that resveratrol inhibits hypoxia-induced oxidative stress and cell proliferation in rat PASMCs possibly through blocking the HIF-1α/NOX4/ROS pathway.

CRISPR/Cas9-mediated disruption of TaNP1 genes results in complete male sterility in bread wheat.

Male sterile genes and mutants are valuable resources in hybrid seed production for monoclinous crops. High genetic redundancy due to allohexaploidy makes it difficult to obtain the nuclear recessive male sterile mutants through spontaneous mutation or chemical or physical mutagenesis methods in wheat. The emerging effective genome editing tool, CRISPR/Cas9 system, makes it possible to achieve simultaneous mutagenesis in multiple homoeoalleles. To improve the genome modification efficiency of the CRISPR/Cas9 system in wheat, we compared four different RNA polymerase (Pol) III promoters (TaU3p, TaU6p, OsU3p, and OsU6p) and three types of sgRNA scaffold in the protoplast system. We show that the TaU3 promoter-driven optimized sgRNA scaffold was most effective. The optimized CRISPR/Cas9 system was used to edit three TaNP1 homoeoalleles, whose orthologs, OsNP1 in rice and ZmIPE1 in maize, encode a putative glucose-methanol-choline oxidoreductase and are required for male sterility. Triple homozygous mutations in TaNP1 genes result in complete male sterility. We further demonstrated that any one wild-type copy of the three TaNP1 genes is sufficient for maintenance of male fertility. Taken together, this study provides an optimized CRISPR/Cas9 vector for wheat genome editing and a complete male sterile mutant for development of a commercially viable hybrid wheat seed production system.

Divergent selection and genetic introgression shape the genome landscape of heterosis in hybrid rice.

The successful application of heterosis in hybrid rice has dramatically improved rice productivity, but the genetic mechanism for heterosis in the hybrid rice remains unclear. In this study, we generated two populations of rice F1 hybrids with present-day commercial hybrid parents, genotyped the parents with 50k SNP chip and genome resequencing, and recorded the phenotype of ∼2,000 hybrids at three field trials. By integrating these data with the collected genotypes of ∼4,200 rice landraces and improved varieties that were reported previously, we found that the male and female parents have different levels of genome introgressions from other rice subpopulations, including indica, aus, and japonica, therefore shaping heterotic loci in the hybrids. Among the introgressed exogenous genome, we found that heterotic loci, including Ghd8/DTH8, Gn1a, and IPA1 existed in wild rice, but were significantly divergently selected among the rice subpopulations, suggesting these loci were subject to environmental adaptation. During modern rice hybrid breeding, heterotic loci were further selected by removing loci with negative effect and fixing loci with positive effect and pyramid breeding. Our results provide insight into the genetic basis underlying the heterosis of elite hybrid rice varieties, which could facilitate a better understanding of heterosis and rice hybrid breeding.

Mapping Collaborations and Partnerships in SDG Research.

Collaboration has become an essential paradigm in sustainable development research and in strategies for meeting the United Nations Sustainable Development Goals (SDGs). This study uses bibliometric methods and network analysis to examine research output and collaboration supporting the SDGs and explores means to detect and analyze research collaboration beyond the traditional definition of multiple, one-time co-authorship. We employed two additional lenses of collaboration: repeat collaboration and collaboration time point to quantify and visualize co-authorship data sourced from Microsoft Academic Graph. Our results show an increased collaboration rate over time at the author and institutional levels; however they also indicate that the majority of collaborations in SDG-related research only happened once. We also found out that on average, repeat collaboration happens more frequently, but after a longer duration, at the institutional level than at the author level. For this reason, we further analyzed institutions and identified core institutions that could help influence more consistent collaboration and sustain or grow the SDG-related research network. Our results have implications for understanding sustainable partnerships in research related to SDGs and other global challenges.

PTK7 expression is associated with lymph node metastasis, ALK and EGFR mutations in lung adenocarcinomas.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death worldwide. Lung adenocarcinoma is the main tumor type of NSCLC. Recent advances in the molecular characterization and personalized therapies have improved NSCLC patient prognosis. Previous studies showed that protein tyrosine kinase 7 (PTK7) plays an important role in human cancers. However, the role of PTK7 has not been investigated. PTK7 expression was assessed by immunohistochemistry in 95 patients with lung adenocarcinoma. Correlations of PTK7 expression levels with clinicopathological parameters, EGFR mutation and EML4-ALK fusion were examined. Positive PTK7 expression was detected in 47.4% of lung adenocarcinoma. PTK7 expression was associated with gender (P=0.024), lymph node metastasis (P<0.001), ALK mutation (P=0.050), and EGFR mutations (P=0.014). No significant association was found between PTK7 expression and age (P=0.831), differentiation (P=0.494), adenocarcinoma subtype (P=0.098) and Ki67 (P=0.473). Our data suggest that PTK7 plays an oncogenic role in lung adenocarcinoma and may be a molecular marker for lymph node metastasis.

Cis-regulated alternative splicing divergence and its potential contribution to environmental responses in Arabidopsis.

Alternative splicing (AS) plays key roles in plant development and the responses of plants to environmental changes. However, the mechanisms underlying AS divergence (differential expression of transcript isoforms resulting from AS) in plant accessions and its contribution to responses to environmental stimuli remain unclear. In this study, we investigated genome-wide variation of AS in Arabidopsis thaliana accessions Col-0, Bur-0, C24, Kro-0 and Ler-1, as well as their F1 hybrids, and characterized the regulatory mechanisms for AS divergence by RNA sequencing. We found that most of the divergent AS events in Arabidopsis accessions were cis-regulated by sequence variation, including those in core splice site and splicing motifs. Many genes that differed in AS between Col-0 and Bur-0 were involved in stimulus responses. Further genome-wide association analyses of 22 environmental variables showed that single nucleotide polymorphisms influencing known splice site strength were also associated with environmental stress responses. These results demonstrate that cis-variation in genomic sequences among Arabidopsis accessions was the dominant contributor to AS divergence, and it may contribute to differences in environmental responses among Arabidopsis accessions.