Genome-wide association study reveals genetic loci for ten trace elements in foxtail millet (Setaria italica).

KEY MESSAGE: One hundred and fifty-five QTL for trace element concentrations in foxtail millet were identified using a genome-wide association study, and a candidate gene associated with Ni-Co-Cr concentrations was detected. Foxtail millet (Setaria italica) is an important regional crop known for its rich mineral nutrient content, which has beneficial effects on human health. We assessed the concentrations of ten trace elements (Ba, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn) in the grain of 408 foxtail millet accessions. Significant differences in the concentrations of five elements (Ba, Co, Ni, Sr, and Zn) were observed between two subpopulations of spring- and summer-sown foxtail millet varieties. Moreover, 84.4% of the element pairs exhibited significant correlations. To identify the genetic factors influencing trace element accumulation, a comprehensive genome-wide association study was conducted, identifying 155 quantitative trait locus (QTL) for the ten trace elements across three different environments. Among them, ten QTL were consistently detected in multiple environments, including qZn2.1, qZn4.4, qCr4.1, qFe6.3, qFe6.5, qCo6.1, qPb7.3, qPb7.5, qBa9.1, and qNi9.1. Thirteen QTL clusters were detected for multiple elements, which partially explained the correlations between elements. Additionally, the different concentrations of five elements between foxtail millet subpopulations were caused by the different frequencies of high-concentration alleles associated with important marker-trait associations. Haplotype analysis identified a candidate gene SETIT_036676mg associated with Ni accumulation, with the GG haplotype significantly increasing Ni-Co-Cr concentrations in foxtail millet. A cleaved amplified polymorphic sequence marker (cNi6676) based on the two haplotypes of SETIT_036676mg was developed and validated. Results of this study provide valuable reference information for the genetic research and improvement of trace element content in foxtail millet.

Transcriptome Profiling Reveals the Gene Network Responding to Low Nitrogen Stress in Wheat.

As one of the essential nutrients for plants, nitrogen (N) has a major impact on the yield and quality of wheat worldwide. Due to chemical fertilizer pollution, it has become increasingly important to improve crop yield by increasing N use efficiency (NUE). Therefore, understanding the response mechanisms to low N (LN) stress is essential for the regulation of NUE in wheat. In this study, LN stress significantly accelerated wheat root growth, but inhibited shoot growth. Further transcriptome analysis showed that 8468 differentially expressed genes (DEGs) responded to LN stress. The roots and shoots displayed opposite response patterns, of which the majority of DEGs in roots were up-regulated (66.15%; 2955/4467), but the majority of DEGs in shoots were down-regulated (71.62%; 3274/4565). GO and KEGG analyses showed that nitrate reductase activity, nitrate assimilation, and N metabolism were significantly enriched in both the roots and shoots. Transcription factor (TF) and protein kinase analysis showed that genes such as MYB-related (38/38 genes) may function in a tissue-specific manner to respond to LN stress. Moreover, 20 out of 107 N signaling homologous genes were differentially expressed in wheat. A total of 47 transcriptome datasets were used for weighted gene co-expression network analysis (17,840 genes), and five TFs were identified as the potential hub regulatory genes involved in the response to LN stress in wheat. Our findings provide insight into the functional mechanisms in response to LN stress and five candidate regulatory genes in wheat. These results will provide a basis for further research on promoting NUE in wheat.

Gastroenteropancreatic neuroendocrine carcinoma in children and adolescents: a population-based study.

PURPOSE: Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC) in children is an exceptionally rare and aggressive form of cancer. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with GEP-NEC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was employed to identify all pediatric patients with GEP-NEC diagnosed between 2000 and 2019. To create survival curves based on various criteria, Kaplane-Meier estimations were utilized. The log-rank test was used to compare survival curves. The variables associated with OS were determined using Cox proportional-hazards regression. Furthermore, we developed a nomogram to predict overall survival in pediatric GEP-NEC patients. RESULTS: A total of 103 pediatric GEP-NEC patients were identified. The tumors primarily affected females (62.2%). The majority of GEP-NEC was found in the appendix (63.1%), followed by the pancreas (23.3%) and the intestinal tract (13.6%). The highest rates of localized stage (76.9%) and surgery (98.5%) were found in the NEC of appendix origin. However, pancreatic origins had the largest proportion of distant disease (66.7%) but the lowest percentage of surgery (37.5%). Overall 1-year, 3-year, and 5-year survival rates for all patients were 94.4%, 85.4%, and 85.4%, respectively. Tumors of pancreatic origin had the worst survival compared with those of the appendix and intestinal tract. The Cox proportional hazard regression revealed that only site was an important independent predictor of survival. CONCLUSIONS: Our study revealed that only the primary site was found to be the most important predictor of the OS in pediatric GEP-NEC. It's important to work closely with a multidisciplinary team, including oncologists, surgeons, and other specialists, to determine the most appropriate treatment plan for pediatric GEP-NEC.

The development of China's Circular Economy: From the perspective of environmental regulation.

While achieving rapid economic growth, the pressure caused by environmental pollution and resource depletion has increasingly become a bottleneck in China's economic development, making the development of a circular economy particularly important. The extant literature has not focused on the influence of environmental regulation on a circular economy performance. This study uses the metafrontier global direction distance function (Metafrontier-Global-DDF) super-efficiency data envelopment analysis (DEA) model to estimate the circular economy performance and decomposition values of circular economy growth rate in 286 prefecture-level cities in China from 2003 to 2018. It further tests the influences of environmental regulations on circular economy performance and its influencing mechanism. The results show that environmental regulation can play a linear role in promoting the performance of the circular economy, mainly through the "catch-up effect," while "innovation effect" and "demonstration effect" have not yet played an effective role. This study provides evidence for the performance evaluation of the circular economy in China and the relationship between environmental regulations and circular economy performance. The future development of a circular economy still needs the active development of circular economy technology in each city. The role of the "innovation effect" and "demonstration effect" in improving the performance of the circular economy should be further enhanced.

A Visualized Isothermal Amplification Method for Rapid and Specific Detection of Emetic and Non-emetic Bacillus cereus in Dairy Products.

Bacillus cereus is widely distributed in foods, especially dairy products, and can lead to diarrhea (non-emetic B. cereus) and emesis (emetic B. cereus). Although diarrhea due to B. cereus is usually mild, emesis can lead to acute encephalopathy and even death. To develop rapid and sensitive detection methods for B. cereus in foods, specific primers targeting the gyrase B (gyrB) and cereulide synthetase (ces) genes were designed and screened using recombinase polymerase amplification (RPA). Probes and base substitutions were introduced to improve specificity and eliminate primer-dependent artifacts. The 5' ends of the reverse primers and probes were modified with biotin and fluorescein isothiocyanate for detection of RPA products on a lateral flow strip (LFS). The developed RPA-LFS assay allows detection within 20 min at 37°C with no cross-reactivity with other foodborne pathogens. The limit of detection was 104 copies/ml and 102 CFU/ml in pure cultures and milk, respectively. Comparisons with established methods using cream obtained similar results. A specific, rapid, and sensitive RPA-LFS assay was successfully developed for on-site detection of B. cereus in dairy products to distinguish emetic from non-emetic strains.

Transcriptome Profile of Fusarium graminearum Treated by Putrescine.

Fusarium graminearum (F. graminearum) is the main pathogen of Fusarium head blight (FHB) in wheat, barley, and corn. Deoxynivalenol (DON), produced by F. graminearum, is the most prevalent toxin associated with FHB. The wheat defense compound putrescine can promote DON production during F. graminearum infection. However, the underlying mechanisms of putrescine-induced DON synthesis are not well-studied. To investigate the effect of putrescine on the global transcriptional regulation of F. graminearum, we treated F. graminearum with putrescine and performed RNA deep sequencing. We found that putrescine can largely affect the transcriptome of F. graminearum. Gene ontology (GO) and KEGG enrichment analysis revealed that having a large amount of DEGs was associated with ribosome biogenesis, carboxylic acid metabolism, glycolysis/gluconeogenesis, and amino acid metabolism pathways. Co-expression analysis showed that 327 genes had similar expression patterns to FgTRI genes and were assigned to the same module. In addition, three transcription factor genes were identified as hub genes in this module, indicating that they may play important roles in DON synthesis. These results provide important clues for further analysis of the molecular mechanisms of putrescine-induced DON synthesis and will facilitate the study of the pathogenic mechanisms of FHB.

The impact of green credit policy on energy efficient utilization in China.

Green credit policy is an innovative measure in the financial industry and can help enterprises reduce energy consumption, reverse the situation of environmental pollution and resource waste, and promote sustainable development of the economy and society based on guiding fund flows into the green environmental protection industry. This research thus uses panel data of 30 provinces and cities in China from 2000 to 2017 to examine the impact of a green credit policy on the level of energy efficient utilization. We establish the EBM (epsilon-based measure) super-efficiency model to measure the level of energy efficient utilization in China, apply the regression discontinuity design (RDD) model to empirically study the net effect of the green credit policy on the level of energy efficient utilization, and assess the policy's regional heterogeneity. Finds present that the level of energy efficient utilization in China exhibits a fluctuating upward trend, and there are certain spatial heterogeneities across its regions. The overall level of the eastern region's energy efficient utilization is the best, followed by the central and western regions in that order. The results of RDD based on the national perspective indicate that the green credit policy has a significantly positive effect on the level of energy efficient utilization, while subregional regression results reveal that improvement caused by implementation of the green credit policy varies across regions in China. The performance of improving energy efficiency in the eastern region is excellent, but the improvement effect in the central and western regions is so far not desirable.

Low-dose apatinib and tegafur-gimeracil-oteracil as palliative treatment in recurrent cervical cancer patients with poor performance status: A case series.

WHAT IS KNOWN AND OBJECTIVE: A large proportion of recurrent cervical cancer (RCC) patients present with poor performance status (PS) after comprehensive treatments, which usually prevents them from opting for clinical trials. We retrospectively analysed the effect and safety of low-dose apatinib and tegafur-gimeracil-oteracil (TGO) in the treatment of these patients. CASE SUMMARY: Six patients treated with low-dose apatinib and TGO showed a disease control rate of 83.3% and grade 1-2 adverse events (AEs). WHAT IS NEW AND CONCLUSION: This case series indicates that low-dose apatinib and TGO could be considered as palliative therapy for RCC patients with poor PS.

Anti­restriction protein KlcAHS enhances carbapenem resistance.

The KlcAHS gene was previously identified as coexisting with the blaKPC­2 gene in the backbone region of a series of blaKPC­2­harboring plasmids. The purpose of the present study was to determine the association between the KlcAHS and blaKPC­2 genes. KlcAHS deletion and complementation experiments were used to evaluate the association between KlcAHS and carbapenem minimal inhibition concentrations (MICs). Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was used to detect changes in the expression levels of blaKPC­2 upon knocking out the KlcAHS gene in a blaKPC­2­harboring plasmid. The imipenem MIC of the transformants harboring ΔKlcAHSpHS10842 was lower (16 µg/ml) than that of the transformants harboring wild­type pHS10842 (32 µg/ml), whereas the kanamycin MIC of the transformants harboring pET24a was lower (1,024 µg/ml) than that of the transformants harboring pET24a­KlcAHS (2,048 µg/ml). The imipenem MICs of the two NM1049 Escherichia coli strains carrying plasmids pHS092839 or ΔKlcAHSpHS092839 exceeded 16 µg/ml, whereas the ertapenem MIC of the host strains harboring ΔKlcAHSpHS092839 was 4 µg/ml compared with ≥8 µg/ml observed in the host strains carrying pHS092839. The RT­qPCR results demonstrated that the messenger RNA expression levels of blaKPC­2 in the transformants carrying ΔKlcAHSpHS092839 were significantly downregulated (P=0.007) compared with those in the transformants carrying pHS092839. These findings revealed that KlcAHS elevated the MIC values of various antibiotics by upregulating the expression levels of blaKPC­2. Therefore, KlcAHS can confer increased resistance to carbapenems in host strains. The survival probability of clinical pathogens may be enhanced by the presence of the KlcAHS gene in antibiotics used on a large scale.

Realization of green transition based on the anti-driving mechanism: An analysis of environmental regulation from the perspective of resource dependence in China.

Environmental regulations and ecological efficiency are the driving force and objective function of China's economic growth, respectively. Whether they can achieve a win-win effect is key to the green transformation and high-quality development of resource-based cities. Based on the normative explanation of the implications of the resource curse, this paper uses panel data to calculate the ecological efficiency level and comprehensive index of environmental regulation by respectively using the global reference of undesirable output super-efficiency SBM model and the entropy method. The spatial panel Durbin model is used to test the Porter and resource curse hypotheses, and whether resource dependence can become the mediating variable of environmental regulation affecting ecological efficiency is further verified by using the mediating effect model. The results show that environmental regulation has a significant U-shaped curve relationship with ecological efficiency and a significant inverted U-shaped curve relationship with resource dependence. The relationship between resource dependence and ecological efficiency is different between resource-based and non-resource-based cities. Resource dependence can be used as a mediating variable of environmental regulation that affects ecological efficiency. Environmental regulation can directly affect the level of ecological efficiency through the mechanisms of "cost of compliance" and "cost-saving innovation," and indirectly the level of ecological efficiency through that of resource dependence. Therefore, there exists an effective "anti-driving mechanism" in China's environmental regulation policy, which can not only promote urban ecological efficiency, but also solve the resource curse of cities.

Evaluating the optimal re-irradiation dose for locally recurrent esophageal squamous cell carcinoma after definitive radiotherapy.

BACKGROUND: Re-irradiation (re-RT) has the active effect of relieving clinical symptoms and prolonging the survival of patients with recurrent esophageal squamous cell carcinoma (ESCC). However, the optimal re-RT dose is still uncertain. Here, we analyzed the prognostic factors associated with survival and explored the optimal re-RT dose for patients with recurrent ESCC following definitive radiotherapy. PATIENTS AND METHODS: The data of 47 patients with recurrent ESCC who were retreated between 2010 and 2014 were retrospectively analyzed. All patients received a radiation dose > 50 Gy during the primary treatment. The median time to recurrence after primary radiotherapy was 26 months (range 6-120 months). All patients had in-field recurrence in the esophagus. Recurrence within the local site was observed in 37 patients (78.7%), and recurrence in both the local site and regional nodes were observed in 10 patients (21.3%). All patients received 3D conformal re-RT with a median dose of 58 Gy (range 26-64 Gy). Chemotherapy was sequentially used in 27.7% of the patients. Survival curves were constructed according to the Kaplan-Meier method and were compared by log-rank tests. The factors predictive of survival were identified with univariate and multivariate analyses. RESULTS: Dysphagia relief after re-RT was achieved in 20 of the 35 symptomatic patients (57.1%). The median survival time (MST) of all patients was 17 months, and the 1-, 2-, 3- and 5-year overall survival (OS) rates were 72.3, 25.5, 17.0 and 2.1%, respectively. In the univariate analysis, an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0-1 (P = 0.014), recurrence at the local site (P = 0.048), time to recurrence ≥24 months (P = 0.006) and re-RT dose ≥50 Gy (P < 0.001) were associated with favorable OS. In the multivariate analysis, only re-RT dose was an independent factor for OS (P = 0.007). Severe complications were observed in 7 patients, two of whom received a re-RT dose > 60 Gy. CONCLUSION: Our results demonstrated that patients with recurrent ESCC following definitive radiotherapy had unfavorable OS. Re-RT could be considered a feasible and effective treatment modality. A re-RT dose > 50 Gy could improve the survival outcomes, and a dose > 60 Gy should be administered with caution due to the risk of severe complications.

Relevance function of microRNA-708 in the pathogenesis of cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally responsible for regulating >70% of human genes. MicroRNA-708 (miR-708) is encoded in the intron 1 of the Odd Oz/ten-m homolog 4 (ODZ4) gene. Numerous researches have confirmed that the abnormal expressed miR-708 is involved in the regulation of multiple types of cancer. Notably, the expression level of miR-708 was higher in lung cancer, bladder cancer (BC) and colorectal cancer (CRC) cell lines while lower in hepatocellular carcinoma (HCC), prostate cancer (PC), gastric cancer (GC) and so on. This review provides a current view on the association between miR-708 and several cancers and focuses on the recent studies of miR-708 regulation, discussing its potential as an epigenetic biomarker and therapeutic target for these cancers. In particular, the regulated mechanisms and clinical application of miR-708 in these cancers are also discussed.

Histone deacetylases function as novel potential therapeutic targets for cancer.

Diverse cellular functions, including tumor suppressor gene expression, DNA repair, cell proliferation and apoptosis, are regulated by histone acetylation and deacetylation. Histone deacetylases (HDACs) are enzymes involved in remodeling of chromatin by deacetylating the lysine residues. They play a pivotal role in epigenetic regulation of gene expression. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation have been implicated in the pathogenesis of various diseases, including cancer. Histone deacetylases have become a target for the development of drugs for treating cancer because of their major contribution to oncogenic cell transformation. Overexpression of HDACs correlates with tumorigenesis. Previous work showed that inhibition of HDACs results in apoptosis and the inhibition of cell proliferation in multiple cells. A significant number of HDAC inhibitors have been developed in the past decade. These inhibitors have strong anticancer effects in vitro and in vivo, inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. In addition, HDAC-mediated deacetylation alters the transcriptional activity of nuclear transcription factors, including p53, E2F, c-Myc, and nuclear factor-κB, as well as the extracellular signal-regulated kinase1/2, phosphatidylinositol 3-kinase, Notch, and Wnt signaling pathways. This review highlights the role of HDACs in cancer pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.

The peroxisome proliferators activated receptor-gamma agonists as therapeutics for the treatment of Alzheimer's disease and mild-to-moderate Alzheimer's disease: a meta-analysis.

Alzheimer's disease (AD) is a devastating neurodegenerative disease and there is no effective therapy for it. Peroxisome proliferators activated receptor-gamma (PPAR-γ) agonists is a promising therapeutic approach for AD and has been widely studied recently, but no consensus was available up to now. To clarify this point, a meta-analysis was performed. We searched MEDLINE, EMBASE, Cochrane Central database, PUBMED, Springer Link database, SDOS database, CBM, CNKI and Wan fang database by December 2014. Standardized mean difference (SMD), relative risk (RR) and 95% confidence interval (CI) were calculated to assess the strength of the novel therapeutics for AD and mild-to-moderate AD. A total of nine studies comprising 1314 patients and 1311 controls were included in the final meta-analysis. We found the effect of PPAR-γ agonists on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) scores by using STATA software. There was no evidence for obvious publication bias in the overall meta-analysis. There is insufficient evidence of statistically incognition of AD and mild-to-moderate AD patients have been improved who were treated with PPAR-γ agonists in our research. However, PPAR-γ agonists may be a promising therapeutic approach in future, especially pioglitazone, with large-scale randomized controlled trials to confirm.

Association of insulin degrading enzyme gene polymorphisms with Alzheimer's disease: a meta-analysis.

Alzheimer's disease (AD) is a chronic degenerative disorder. It is caused by both genetic and environmental factors. The association of Insulin Degrading Enzyme (IDE) genotypes rs4646953, rs2251101 and rs1544210 with AD has been detected, but the findings were conflicted, however, Apolipoprotein-E (APOE)-ε4 allele has been observed as a genetic risk factor for AD. To investigate the issue, a meta-analysis was performed. We searched PubMed, Springer Link, AlzGene and CNKI for relevant literatures published by June 2013. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to explore the significant association. A total of 11 studies comprising 5771 cases and 5474 controls were considered in final meta-analysis. We found that weak connections existed between rs4646953 (TT vs. CC: z = 2.24, p = 0.025, OR = 1.536) and AD, but no significant associations have been found between other IDE gene single nucleotide polymorphisms of rs4646953, rs2251101 and rs1544210 with AD. We certified that APOE-ε4 allele was still be a suspected factor to AD. There was no evidence for obvious publication bias in overall meta-analysis. Furthermore, larger-scale randomized controlled trials are necessary to validate the association between IDE gene polymorphisms with AD.