Biofortification of iron content by regulating a NAC transcription factor in maize.

Iron (Fe) deficiency remains widespread among people in developing countries. To help solve this problem, breeders have been attempting to develop maize cultivars with high yields and high Fe concentrations in the kernels. We conducted a genome-wide association study and identified a gene, ZmNAC78 (NAM/ATAF/CUC DOMAIN TRANSCRIPTION FACTOR 78), that regulates Fe concentrations in maize kernels. We cultivated maize varieties with both high yield and high Fe concentrations in their kernels by using a molecular marker developed from a 42-base pair insertion or deletion (indel) in the promoter of ZmNAC78. ZmNAC78 expression is enriched in the basal endosperm transfer layer of kernels, and the ZmNAC78 protein directly regulates messenger RNA abundance of Fe transporters. Our results thus provide an approach to develop maize varieties with Fe-enriched kernels.

MIR164b represses iron uptake by regulating the NAC domain transcription factor5-Nuclear Factor Y, Subunit A8 module in Arabidopsis.

Recent findings have revealed the important roles of microRNAs (miRNAs) in the secondary responses to oxidative damage caused by iron (Fe) excess. However, the functional importance of miRNAs in plant responses to Fe deficiency remains to be explored. Here, we show that the expression level of miR164 in Arabidopsis (Arabidopsis thaliana) roots was repressed by Fe deficiency. Primary root length, lateral root number, ferric reductase activity, and mRNA abundance of IRON-REGULATED TRANSPORTER1 (IRT1) and FERRIC REDUCTION OXIDASE2 (FRO2) were higher in the mir164b mutant than in the wild-type (WT) under Fe-deficient conditions. Analysis of the Fe concentrations and ferric reductase activities in the roots of miR164 knockdown transgenic plants showed that members of the miR164 family had different functions in Fe-deficiency responses. Promoter::GUS analysis showed that NAM/ATAF/CUC (NAC) domain transcription factor5 (NAC5) is regulated at both transcriptional and posttranscriptional levels under Fe-deficient conditions. Transgenic Arabidopsis plants overexpressing NAC5 were more tolerant of Fe deficiency than the WT. NAC5 has transactivation activity and directly transactivates the expression of Nuclear Factor Y, Subunit A8 (NFYA8), as demonstrated by chromatin immunoprecipitation followed by quantitative polymerase chain reaction, electrophoretic mobility shift assay (EMSA), and dual-luciferase reporter assay. Like overexpression of NAC5, overexpression of NFYA8 increases primary root length, lateral root number, ferric reductase activity, and mRNA abundance of IRT1 and FRO2 under Fe-deficient conditions. Thus, MIR164b is important for Fe-deficiency responses by its regulation of the NAC5-NFYA8 module.

The PILNCR1-miR399 Regulatory Module Is Important for Low Phosphate Tolerance in Maize.

The regulation of adaptive responses to phosphorus (P) deficiency by the microRNA399 (miR399)/PHOSPHATE2 (PHO2) pathway has been well studied in Arabidopsis (Arabidopsis thaliana) but not in maize (Zea mays). Here, we show that miR399 transcripts are strongly induced in maize by phosphate (Pi) deficiency. Transgenic maize plants that overexpressed MIR399b accumulated excessive amounts of P in their shoots and displayed typical Pi-toxicity phenotypes. We reannotated ZmPHO2 with an additional 1,165 bp of the 5' untranslated region. miR399-guided posttranscriptional repression of ZmPHO2 was mainly observed in the P-efficient lines. We identified Pi-deficiency-induced long-noncoding RNA1 (PILNCR1) from our strand-specific RNA libraries. Transient expression assays in Nicotiana benthamiana and maize leaf protoplasts demonstrated that PILNCR1 inhibits ZmmiR399-guided cleavage of ZmPHO2 The abundance of PILNCR1 was significantly higher in P-inefficient lines than in P-efficient lines, which is consistent with the abundance of ZmmiR399 transcripts. These results indicate that the interaction between PILNCR1 and miR399 is important for tolerance to low Pi in maize.

ROR2 inhibits the proliferation of gastric carcinoma cells via activation of non-canonical Wnt signaling.

Gastric carcinoma is one of the most common human cancers and has a poor prognosis. Receptor tyrosine kinase-like orphan receptor 2 (ROR2), which is a non-canonical receptor of the Wnt signaling pathway, has been reported to be deregulated in numerous types of human cancers, including gastric carcinoma. However, the exact role of ROR2 in the regulation of the malignant phenotypes of gastric carcinoma, as well as the underlying molecular mechanism, remains largely unclear. The present study demonstrated that ROR2 was recurrently downregulated in gastric carcinoma tissues, as compared with their matched adjacent normal tissues. Furthermore, the expression levels of ROR2 were reduced in several common gastric carcinoma cell lines, as compared with normal gastric epithelial cells. Gastric carcinoma cells were transfected with ROR2 plasmids, and it was demonstrated that restoration of ROR2 expression significantly inhibited the proliferation and induced the apoptosis of gastric carcinoma cells by a Wnt5a-independent mechanism. In addition, it was observed that ROR2-overexpressing cells accumulated in the G0/G1 phase; thus suggesting that overexpression of ROR2 induced cell cycle arrest at the G0/G1 phase. An investigation of the underlying mechanism demonstrated that activation of the non-canonical Wnt signaling pathway inhibited canonical Wnt signal transduction, as demonstrated by the decreased level of ß-catenin in nuclei, as well as the reduced expression levels of c-Myc. The results of the present study indicated a tumor suppressive role for ROR2 in gastric carcinoma growth in vitro, and suggested that ROR2 may be used as a molecular target for the treatment of gastric carcinoma.

SYNJ2 variant rs9365723 is associated with colorectal cancer risk in Chinese Han population.

PURPOSE: Colorectal cancer (CRC) is the third most common cancer and fourth leading cause of cancer mortality, and twin studies have shown that approximately 35% of the variation in susceptibility to CRC involves inherited genetic differences. We sought to investigate potential genetic associations between some single nucleotide polymorphisms (SNPs) and the risk of CRC in the Chinese Han population. METHODS: We conducted a case-control study including 269 cases and 309 controls. Sixteen SNPs associated with CRC risk were selected from previous genome-wide association studies and genotyped using Sequenom MassARRAY technology. Odds ratios and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and gender. RESULTS: Using the chi-squared test we found that rs9365723 was associated with CRC risk (p = 0.012). With genetic model analysis, the genotype A/G-G/G (OR = 1.50; 95% CI 1.02-2.21; p = 0.038) of rs9365723 showed an increased risk of CRC in the dominant model. Furthermore, we found that rs9365723 was associated with an increased risk only for colon cancer but not rectal cancer (p = 0.009 and p = 0.414, respectively). CONCLUSIONS: Our results, combined with previous studies, suggest that rs9365723, located on SYNJ2, is associated with the risk of CRC in a Chinese population. Thus, SYNJ2 may play a role in the development of CRC, especially colon cancer.

[Efficacy comparison of laparoscopic versus open tension-free hernia repair using biologic mesh for inguinal strangulated hernia].

OBJECTIVE: To compare the efficacy of laparoscopic versus open tension-free mesh repair using biologic mesh for inguinal strangulated hernia. METHODS: Clinical data of 27 patients with inguinal strangulated hernia in the Shanxi Provincial People's Hospital between January 2012 and April 2014 were analyzed retrospectively. All the patients underwent one-stage tension-free repair using biological mesh, including laparoscopic(n=13) and open procedures(n=14). RESULTS: As compared with the open group, the laparoscopic group had shorter operative time [(90.8±11.6) min vs. (130.8±32.5) min, P<0.01], lower rates of hematoma/seroma and wound infection[(7.7% vs. 42.9%) and (0 vs. 28.6%) respectively, both P<0.05], faster recovery of bowel function [(2.5±0.3) d vs. (3.8±1.4) d, P<0.01], and shorter hospital stay [(6.3±1.8) d vs. (9.8±3.2) d, P<0.01]. The mean follow-up was 5.7 months (ranged from 2 to 12 months), and no recurrence or serious complications occurred. CONCLUSION: Laparoscopic tension-free hernia repair using biological mesh for inguinal strangulated hernia has significant advantage versus open operation.

DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese population.

Dual-specificity protein phosphatases (DUSP) negatively regulate members of the mitogen-activated protein kinase superfamily, which is associated with cellular proliferation and differentiation. A recent study suggests that DUSP10 is frequently upregulated in colorectal cancer (CRC). Our study aimed to assess whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese by the χ²-test and the SHEsis software. We found that two tSNPs (rs908858, P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using the χ²-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629, rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype 'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ∼53%; the haplotype 'GCCCACCCA' may decrease the risk by ∼46%. Our results, combined with previous studies, suggest that certain mutations in DUSP10 correlate with the incidence of CRC. Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population.

[Early change of pulmonary ventilation in new coal miners].

OBJECTIVE: To study the early effects of coal dust on lung function in new underground coal miners. METHODS: Two hundred and eighty-seven male miners were selected from new employees at the Xuzhou Mining Group Company as study group, and 132 male students at a mining technical school were selected as control. Data collection included: individual demographic parameters, family medical history, occupational history, and smoking history, measurement of dust concentrations in work areas, and lung function tests. This prospective cohort study took place over 3 years during which time total dust and respirable dust concentrations in the new coal miners' work areas were measured twice each month. For both miner and student groups, FVC and FEV(1) were tested initially before dust exposure, and then 15 times over the 3 years. RESULTS: The average total dust and respirable dust concentrations in the miners' work areas were 23.8 mg/m(3) and 8.9 mg/m(3) respectively, which greatly exceeded national health criteria. During the first year of dust exposure, the miners's average FVC was higher than that of the controls (5.19 L vs 4.92 L, P < 0.01). During the 2nd and 3rd year the difference in average FVC between miners and control group was not significant (5.14 L vs 5.12 L, P > 0.05). Before dust exposure, the miners' FEV(1) was significantly higher than that of the control group (4.48 L vs 4.28 L). In the miners group, FEV(1) declined rapidly during the first year following dust exposure (from 4.48 L to 4.25 L), and in the 2nd and the 3rd year the average FEV(1) of the miners was significantly lower than that of controls (4.34 L vs 4.56 L, P < 0.01), although there were some fluctuations during the follow-up period. Overall, the average FEV(1) of miners group showed a significant decline during the study. There were significant correlations between FVC or FEV(1) and age, height, weight, and smoking. The three-year total loss of FVC and FEV(1) in smoking miners (154 ml, 184 ml) were greater than in non-smoking miners (83 ml, 91 ml). CONCLUSION: There are apparent effects of coal dust on lung function in new underground coal miners, with FEV(1) being more impacted than FVC. Smoking may aggravate the effect of dust exposure on reducing lung function.

[Analyses of 1003 death cases of pneumoconiosis from Xuzhou coal mines].

In order to investigate the general rules concerning attack, development and death of pneumoconiosis for providing scientific evidences for preventing, 1003 death cases of pneumoconiosis from Xuzhou coal mine factory were analyzed. Results showed that: (1) The death causes was in the sequence of pneumoconiosis, lung tuberculosis, chronic cor pulmonale, pulmonary carcinoma, etc., and changed into pneumoconiosis, chronic cor pulmonale, pulmonary carcinoma, cerebrovascular accident, etc. since 1990s. Lung tuberculosis would no longer be the main death cause of pneumoconiosis; (2) The accumulative death percentage of the death cases about pneumoconiosis was correlated to the length of dust exposure. The accumulative death percentage increased rapidly in a beeline within 5 to 20 years; (3) The length of service of episode and mean life of digging or mining workers were significantly shorter than that of others (P < 0.01); (4) The mean life and the course of diseases became more and more longer than ever since 1970s. Therefore, it can be concluded that the key for preventing and controlling pneumoconiosis was to decrease the concentration of dust in workplace and to limit the length of service of dust exposure.