Long-term MNNG exposure promotes gastric carcinogenesis by activating METTL3/m6A/miR1184 axis-mediated epithelial-mesenchymal transition.

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

Comparative Genomics and Gene Pool Analysis Reveal the Decrease of Genome Diversity and Gene Number in Rice Blast Fungi by Stable Adaption with Rice.

Magnaporthe oryzae caused huge losses in rice and wheat production worldwide. Comparing to long-term co-evolution history with rice, wheat-infecting isolates were new-emerging. To reveal the genetic differences between rice and wheat blast on global genomic scale, 109 whole-genome sequences of M. oryzae from rice, wheat, and other hosts were reanalyzed in this study. We found that the rice lineage had gone through stronger selective sweep and fewer conserved genes than those of Triticum and Lolium lineages, which indicated that rice blast fungi adapted to rice by gene loss and rapid evolution of specific loci. Furthermore, 228 genes associated with host adaptation of M. oryzae were found by presence/absence variation (PAV) analyses. The functional annotation of these genes found that the fine turning of genes gain/loss involved with transport and transcription factor, thiol metabolism, and nucleotide metabolism respectively are major mechanisms for rice adaption. This result implies that genetic base of specific host plant may lead to gene gain/loss variation of pathogens, so as to enhance their adaptability to host. Further characterization of these specific loci and their roles in adaption and evaluation of the fungi may eventually lead to understanding of interaction mechanism and develop new strategies of the disease management.

The expression pattern of OsDim1 in rice and its proposed function.

Development of plant tissues is dependent on numerous factors, including hormone activity, signaling, cell division, and elongation. In plants, Defective Entry into Mitosis 1 (Dim1) homologs are recognized as pivotal in leaf senescence and progress of normal growth, but their role in rice has not been functionally characterized. The findings presented in this paper suggest that OsDim1 is important in early seedling development, pollen tube elongation, and impacts rice yield components. The gene is expressed in the scutellum, endosperm, embryonic root, shoot, pollen grains and tubes, as well as in several organs of the rice flower. According to the present study findings, RNAi mediated knockdown of OsDim1 resulted in phytohormonal imbalance, reduced amylase activity, affected differentiation of embryonic root elongation zone tissues, suppressed embryonic root and shoot growth, and impaired pollen tube elongation. In contrast, overexpression of OsDim1 showed significant growth in embryonic roots and shoots, while it increased culm length, total number of tillers per plant, seed setting rate, and total number of grains per panicle compared to its wild type line. In summary, we propose OsDim1 plays an important role in seedling growth and pollen tube elongation, and has pleiotropic effects on reproductive tissues.

Griseaketides A-D, New Aromatic Polyketides from the Pathogenic Fungus Magnaporthe grisea.

Magnaporthe grisea is the causal agent of rice blast disease, which is the most serious disease of cultivated rice. Aromatic polyketides are its typical metabolites and are involved in the infection process. In the search for novel lead compounds, chemical investigation of the fungus M. grisea M639 has led to the isolation of four new aromatic polyketides (salicylaldehyde skeleton bearing an unsaturated side chain), griseaketides A-D (1-4), as well as 15 known compounds (5-19). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including HR-MS, 2D NMR. Compound 12 showed prominent activity that killed 94.5% of C. elegans at 400 ppm and 66.9% at 200 ppm over 24 h. This is the first report describing the nematicidal activity of this type aromatic polyketide.

Integrated analysis highlights multiple long non­coding RNAs and their potential roles in the progression of human esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent aggressive malignant tumor with poor prognosis. Investigations into the molecular changes that occur as a result of the disease, as well as identification of novel biomarkers for its diagnosis and prognosis, are urgently required. Long non­coding RNAs (lncRNAs) have been reported to play a critical role in tumor progression. The present study performed data mining analyses for ESCC via an integrated study of accumulated datasets and identification of the differentially expressed lncRNAs from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The identified intersection of differentially expressed genes (lncRNAs, miRNAs and mRNAs) in ESCC tissues between the GEO and TCGA datasets was investigated. Based on these intersected lncRNAs, the present study constructed a competitive endogenous RNA (ceRNA) network of lncRNAs in ESCC. A total of 81 intersection lncRNAs were identified; 67 of these were included in the ceRNA network. Functional analyses revealed that these 67 key lncRNAs primarily dominated cellular biological processes. The present study then analyzed the associations between the expression levels of these 67 key lncRNAs and the clinicopathological characteristics of the ESCC patients, as well as their survival time using TCGA. The results revealed that 31 of these lncRNAs were associated with tumor grade, tumor­node­metastasis (TNM) stage and lymphatic metastasis status (P<0.05). In addition, 15 key lncRNAs were demonstrated to be associated with survival time (P<0.05). Finally, 5 key lncRNAs were selected for validation of their expression levels in 30 patients newly diagnosed with ESCC via reverse transcription­quantitative PCR (RT­qPCR). The results suggested that the fold changes in the trends of up­ and downregulation between GEO, TCGA and RT­qPCR were consistent. In addition, it was also demonstrated that a select few of these 5 key lncRNAs were significantly associated with TNM stage and lymph node metastasis (P<0.05). The results of the clinically relevant analysis and the aforementioned bioinformatics were similar, hence proving that the bioinformatics analysis used in the present study is credible. Overall, the results from the present study may provide further insight into the functional characteristics of lncRNAs in ESCC through bioinformatics integrative analysis of the GEO and TCGA datasets, and reveal potential diagnostic and prognostic biomarkers for ESCC.

Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics.

BACKGROUND: MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA). METHODS: Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study. RESULTS: Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar. CONCLUSION: This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.

A novel discovery of a long terminal repeat retrotransposon-induced hybrid weakness in rice.

Hybrid weakness is a post-zygotic hybridization barrier frequently observed in plants, including rice. In this study, we describe the genomic variation among three temperate japonica rice (Oryza sativa ssp. japonica) varieties 'Aranghyangchalbyeo' ('CH7'), 'Sanghaehyangheolua' ('CH8') and 'Shinseonchalbyeo' ('CH9'), carrying different hybrid weakness genes. The reciprocal progeny obtained from crossing any two varieties displayed characteristic hybrid weakness traits. We mapped and cloned a new locus, Hwc3 (hybrid weakness 3), on chromosome 4. Sequence analysis identified that a long terminal repeat (LTR) retrotransposon was inserted into the promoter region of the Hwc3 gene in 'CH7'. A 4-kb DNA fragment from 'CH7' containing the Hwc3 gene with the inserted LTR retrotransposon was able to induce hybrid weakness in hybrids with 'CH8' plants carrying the Hwc1 gene by genetic complementation. We investigated the differential gene expression profile of F1 plants exhibiting hybrid weakness and detected that the genes associated with energy metabolism were significantly down-regulated compared with the parents. Based on our results, we propose that LTR retrotransposons could be a potential cause of hybrid weakness in intrasubspecific hybrids in japonica rice. Understanding the molecular mechanisms underlying intrasubspecific hybrid weakness is important for increasing our knowledge on reproductive isolation and could have significant implications for rice improvement and hybrid breeding.

Identification and functional characterization of long non-coding RNAs in human gastric cancer.

Abnormal regulation of long non-coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non-tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non-tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that RP5-919F19, MCPH1 antisense RNA 1 (CTD-2541M15) and urothelial carcinoma-associated 1 (UCA1) exhibited consistent upregulation in cancer compared with adjacent non-tumor tissues, whereas AP000459, LOC101928316, tumor suppressor candidate 8 (LINC01071) and maternally expressed 3 (MEG3) showed consistent downregulation. The results from the microarray and RT-qPCR experiments achieved 100% agreement. A correlation analysis indicated that RP5-919F19, LOC101928316 and MEG3 were significantly associated with tumor differentiation degree, RP5-919F19, UCA1 and MEG3 were significantly associated with lymph node metastasis, and RP5-919F19, CTD-2541M15 and UCA1 were significantly associated with tumor-node-metastasis stage (P<0.05). In addition, it was identified that the differential expression of LINC01071 and LOC101928316 significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs RP5-919F19, LOC101928316, CTD-2541M15, UCA1 and MEG3 are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy.

Integrated analysis of long non­coding RNA competing interactions revealed potential biomarkers in cervical cancer: Based on a public database.

Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Using an RNA sequencing profile from The Cancer Genome Atlas (TCGA) and the CC patient information, the aim of the present study was to identify potential long non­coding RNA (lncRNA) biomarkers of CC using bioinformatics analysis and building a competing endogenous RNA (ceRNA) co­expression network. Results indicated several CC­specific lncRNAs, which were associated with CC clinical information and selected some of them for validation and evaluated their diagnostic values. Bioinformatics analysis identified 51 CC­specific lncRNAs (fold­change >2 and P<0.05), and 42 of these were included in ceRNA network consisting of lncRNA­miRNA­mRNA interactions. Further analyses revealed that differential expression levels of 19 lncRNAs were significantly associated with different clinical features (P<0.05). A total of 11 key lncRNAs in the ceRNA network for reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis to detect their expression levels in 31 pairs of CC clinical samples. The results indicated that 7 lncRNAs were upregulated and 4 lncRNAs were downregulated in CC patients. The fold­changes between the RT­qPCR experiments and the TCGA bioinformatics analyses were the same. Furthermore, the area under the receiver operating characteristic (ROC) curve of four lncRNAs (EMX20S, MEG3, SYS1­DBNDD2 and MIR9­3HG) indicated that their combined use may have a significant diagnostic value in CC (P<0.05). To the best of our knowledge, the present study is the first to have identified CC­specific lncRNAs to construct a ceRNA network and has also provided new insights for further investigation of a lncRNA­associated ceRNA network in CC. In additon, the verification results suggested that the method of bioinformatics analysis and screening of lncRNAs was accurate and reliable. To conclude, the use of multiple lncRNAs may thus improve diagnostic efficacy in CC. In addition, these specific lncRNAs may serve as new candidate biomarkers for clinical diagnosis, classification and prognosis of CC.

Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region, China, 2018.

Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends (+2.63% per year; P < 0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.

Integrated analysis of competing endogenous RNA network revealing lncRNAs as potential prognostic biomarkers in human lung squamous cell carcinoma.

Accumulating evidence shows the important role of long non-coding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks for predicting survival in tumor patients. However, prognostic biomarkers for lung squamous cell carcinoma (LUSC) are still lacking. The objective of this study is to identify a lncRNA signature for evaluation of overall survival (OS) in 474 LUSC patients from The Cancer Genome Atlas (TCGA) database. A total of 474 RNA sequencing profiles in LUSC patients with clinical data were obtained, providing a large sample of RNA sequencing data, and 83 LUSC-specific lncRNAs, 26 miRNAs, and 85 mRNAs were identified to construct the ceRNA network (fold change>2, P<0.05). Among these above 83 LUSC-specific lncRNAs, 22 were assessed as closely related to OS in LUSC patients using a univariate Cox proportional regression model. Meanwhile, two (FMO6P and PRR26) of the above 22 OS-related lncRNAs were identified using a multivariate Cox regression model to construct a risk score as an independent indicator of the prognostic value of the lncRNA signature in LUSC patients. LUSC patients with low-risk scores were more positively correlated with OS (P<0.001). The present study provides a deeper understanding of the lncRNA-related ceRNA network in LUSC and suggests that the two-lncRNA signature could serve as an independent biomarker for prognosis of LUSC.

A LysM Domain-Containing Gene OsEMSA1 Involved in Embryo sac Development in Rice (Oryza sativa L.).

The embryo sac plays a vital role in sexual reproduction of angiosperms. LysM domain containing proteins with multiple lysin motifs are widespread proteins and are involved in plant defense responses against fungal chitins and bacterial peptidoglycans. Various studies have reported the role of LysM domain-containing proteins in plant defense mechanisms but their involvement in sexual reproduction remains largely unknown. Here, we report the involvement of a LysM domain-containing gene, EMBRYO SAC 1 (OsEMSA1), in the sexual reproduction of rice. The gene encoded a LysM domain-containing protein that was necessary for embryo sac development and function. The gene was expressed in root, stem, leaf tissues, panicle and ovaries and had some putative role in hormone regulation. Suppression of OsEMSA1 expression resulted in a defective embryo sac with poor differentiation of gametophytic cells, which consequently failed to attract pollen tubes and so reduced the panicle seed-setting rate. Our data offers new insight into the functions of LysM domain-containing proteins in rice.

Comprehensive analysis of aberrantly expressed microRNA profiles reveals potential biomarkers of human lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is a complex disease that poses challenges for diagnosis and treatment. The aim of the present study is to investigate LUAD-specific key microRNAs (miRNAs) from large-scale samples in The Cancer Genome Atlas (TCGA) database. We used an integrative computational method to identify LUAD-specific key miRNAs related to TNM stage and lymphatic metastasis from the TCGA database. Twenty-five LUAD-specific key miRNAs (fold change >2, p<0.05) from the TCGA database were investigated, and 15 were found to be aberrantly expressed with respect to clinical features. Three miRNAs were correlated with overall survival (log-rank p<0.05). Then, 5 miRNAs were randomly selected for verification of expression in 53 LUAD patient tissues using qRT-PCR. Diagnostic value of these above 5 miRNAs was determined by areas under receiver operating characteristic curves (ROC). Finally, the LUAD-related miRNA miR-30a-3p was selected for verification of biologic function in A549 cells. The results of tests for cell proliferation, apoptosis, and target genes suggested that miR-30a-3p decreases cell proliferation and promotes apoptosis through targeting AKT3. Therefore, miR-30a-3p may be a promising biomarker for the early screening of high-risk populations and early diagnosis of LUAD. Our studies provide insights into identifying novel potential biomarkers for diagnosis and prognosis of LUAD.

Integrated analysis of long non-coding RNA­associated ceRNA network reveals potential lncRNA biomarkers in human lung adenocarcinoma.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p<0.05) were identified. Then, the lncRNA-miRNA-mRNA ceRNA network of LUAD was constructed with 29 key lncRNAs, 24 miRNAs and 72 mRNAs. Subsequently, we selected these 29 key lncRNAs to analyze their correlation with clinical features, and 21 of them were aberrantly expressed with tumor pathological stage, TNM staging system, lymph node metastasis and patient outcome assessment, respectively. Furthermore, there were 5 lncRNAs (BCRP3, LINC00472, CHIAP2, BMS1P20 and UNQ6494) positively correlated with overall survival (OS, log-rank p<0.05). Finally, 7 cancer specific lncRNAs were randomly selected to verify the expression in 53 newly diagnosed LUAD patients using qRT-PCR. The expression results between TCGA and qRT-PCR were 100% in agreement. The correlation between AFAP1-AS1 and LINC00472 and clinical features were also confirmed. Thus, our results showed the lncRNA expression profiles and we constructed an lncRNA-miRNA-mRNA ceRNA network in LUAD. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in LUAD and facilitates the identification of potential biomarkers for diagnosis and prognosis.

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer.

Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05). The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis.

Cancer Incidence and Mortality Survey in Wuwei, Gansu Province, Northwestern China from 2003 to 2012: A Retrospective Population-based Study.

BACKGROUND: Population-based cancer registry collects the data on cancer incidence and mortality deaths from covered population to describe and survey the epidemics in certain areas. The aim of this study was to estimate the cancer incidence and mortality in Wuwei, Gansu province, Northwestern China from 2003 to 2012. The goal is to better understand cancer distribution and long-term development of cancer prevention and treatment in Wuwei. METHODS: Data were collected from the Wuwei Cancer Registry between 2003 and 2012. In this registry, data from 46 cancer report centers were included in this analysis. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, and cumulative incidence/mortality rates were calculated. Totally, 9,836,740 person-years (5,110,342 for males and 4,726,398 for females) had been monitored over this time period. The gender ratio of male/female was 1.08:1. The number of new cancer cases and related deaths was 24,705 and 17,287 from 2003 to 2012, respectively. RESULTS: The proportion of morphological verification was 74.43%. The incidence of cases identified through death certification only was 1.21%, and the mortality to incidence ratio was 0.70. The average crude incidence was 251.15/100,000 persons (310.61 and 186.87 for males and females per 100,000 persons, respectively). The age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 207.76 and 245.42 per 100,000 persons, respectively. The crude cancer mortality was 175.74/100,000 persons (228.34 and 118.86 for males and females per 100,000 persons). ASR for China and the world was 149.57 and 175.13/100,000 persons, respectively. The most common cancers and leading causes of cancer-related deaths in Wuwei were as follows: cancers of stomach, esophagus, liver, lung, colorectum, breast, cervix, lymphoma, blood (leukemia), brain, and central nervous system. In Wuwei, during 2003 and 2012, cancer incidence and mortality rates increased by 1.32% and 1.31%/year, respectively. During this time, colorectum cancer incidence and mortality rates increased by 2.69% and 7.54%/year, respectively, in Wuwei. The incidence and mortality of other gastric, esophageal, liver, and lung cancers also all increased. CONCLUSIONS: The results of this study report a more accurate cancer burden among the population of Wuwei, China. Active research of cancers etiology and effective prevention should be established to reduce the incidence and mortality associated with cancers.

Endoplasmic reticulum protein 29 protects cortical neurons from apoptosis and promoting corticospinal tract regeneration to improve neural behavior via caspase and Erk signal in rats with spinal cord transection.

Following spinal cord injury (SCI), limit spontaneous functional recovery often emerged. However, the neuronal mechanisms associated with this phenomenon still remains obscure. By using proteomics analysis, endoplasmic reticulum protein 29 (ERp29) was discovered to increase in the motor cortexes of spinal cord transection (SCT) rats for 28 days post-operation (dpo) compared with in 14dpo. Then, the change in the expression of ERp29 was confirmed by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To determine the role of ERp29 in the recovery of locomotor functions following SCT, lentiviral vectors were used to up- and downregulate the expression level of ERp29. Here, we found that cortical neurons in vitro with high level of ERp29 expression exhibited a significant proliferation, characterized by smaller size of soma and more extensive axon outgrowth, compared with neurons used as control, while ERp29 silence got the opposite results. In vivo, Lentivirus was inject into the cerebral cortex following SCT at thoracic level 10, which resulted in an increase number of neuronal nuclei(NeuN)-positive cells and less apoptotic cells. Moreover, increased PKC-γ immunoreactivity density was also found in the spinal cord T9 level compared with control rats. This was associated with a great functional improvement, indicated by Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Lastly, we verified that ERp29 acts as a regulator by regulating a group of genes related with cell survival and apoptosis, involving in caspase and Erk, but not PI3K. Our findings showed that ERp29 can improve locomotor function by promoting neuronal survival and axonal regeneration in SCT rats via caspase and Erk signal pathway.

The expression and phylogenetic analysis of four AP3-like paralogs in the stamens, carpels, and single-whorl perianth of the paleoherb Asarum caudigerum.

The paleoherb species Asarum caudigerum (Aristolochiaceae) is important for research into the origin and evolution of angiosperm flowers due to its basal position in the angiosperm phylogeny. In this study, four MADS-box-containing transcripts were isolated from A. caudigerum by rapid amplification of cDNA ends (RACE). Sequence comparisons and phylogenetic analyses indicated that they possess high homology to AP3 subfamily genes, which have been shown previously to be involved in petal and stamen development in eudicots. Reverse-transcription quantitative PCR (RT-qPCR) and in situ hybridization analyses showed AcAP3-A expression mainly in the second whorl (stamens) and AcAP3-B expression in whorls 1 and 3 (perianth and carpels). Compared with eudicot AP3 homologs, premature translation termination codons were caused by an insertion in the K1 domain of AcAP3-C, and by a deletion in the 7th exon of AcAP3-D. Sequence analyses suggested that the A. caudigerum AP3 lineage had undergone gene duplication and subfunctionalization, diverging in expression patterns during perianth, stamen, and carpel development. Based on comparative genomic and phylogenetic analyses, we concluded that subfunctionalization has likely contributed to the persistence of two functional AP3 paralogs, that two other copies may have become pseudogenes, and that these AP3 duplication and subfunctionalization events may have contributed to the evolution of the unusual floral morphology of A. caudigerum.

The Bsister MADS gene FST determines ovule patterning and development of the zygotic embryo and endosperm.

Many homeotic MADS-box genes have been identified as controllers of the floral transition and floral development. However, information regarding Bsister (Bs)-function genes in monocots is still limited. Here, we describe the functional characterization of a Bs-group MADS-box gene FEMALE-STERILE (FST), whose frame-shift mutation (fst) results in abnormal ovules and the complete abortion of zygotic embryos and endosperms in rice. Anatomical analysis showed that the defective development in the fst mutant exclusively occurred in sporophytic tissues including integuments, fertilized proembryos and endosperms. Analyses of the spatio-temporal expression pattern revealed that the prominent FST gene products accumulated in the inner integument, nucellar cell of the micropylar side, apical and base of the proembryos and free endosperm nuclei. Microarray and gene ontology analysis unraveled substantial changes in the expression level of many genes in the fst mutant ovules and seeds, with a subset of genes involved in several developmental and hormonal pathways appearing to be down-regulated. Using both forward and reverse genetics approaches, we demonstrated that rice FST plays indispensable roles and multiple functions during ovule and early seed development. These findings support a novel function for the Bs-group MADS-box genes in plants.

Developmental genetics of the perianthless flowers and bracts of a paleoherb species, Saururus chinensis.

Saururus chinensis is a core member of Saururaceae, a perianthless (lacking petals or sepals) family. Due to its basal phylogenetic position and unusual floral composition, study of this plant family is important for understanding the origin and evolution of perianthless flowers and petaloid bracts among angiosperm species. To isolate genes involved in S. chinensis flower development, subtracted floral cDNA libraries were constructed by using suppression subtractive hybridization (SSH) on transcripts isolated from developing inflorescences and seedling leaves. The subtracted cDNA libraries contained a total of 1,141 ESTs and were used to create cDNA microarrays to analyze transcript profiles of developing inflorescence tissues. Subsequently, qRT-PCR analyses of eight MADS-box transcription factors and in situ hybridizations of two B-class MADS-box transcription factors were performed to verify and extend the cDNA microarray results. Finally, putative phylogenetic relationships within the B-class MADS-box gene family were determined using the discovered S. chinensis B-class genes to compare K-domain sequences with B genes from other basal angiosperms. Two hundred seventy-seven of the 1,141 genes were found to be expressed differentially between S. chinensis inflorescence tissues and seedling leaves, 176 of which were grouped into at least one functional category, including transcription (14.75%), energy (12.59%), metabolism (9.12%), protein-related function (8.99%), and cellular transport (5.76%). qRT-PCR and in situ hybridization of selected MADS-box genes supported our microarray data. Phylogenetic analysis indicated that a total of six B-class MADS-box genes were isolated from S. chinensis. The differential regulation of S. chinensis B-class MADS-box transcription factors likely plays a role during the development of subtending bracts and perianthless flowers. This study contributes to our understanding of inflorescence development in Saururus, and represents an initial step toward understanding the formation of petaloid bracts in this species.