Transcription factors MhDREB2A/MhZAT10 play a role in drought and cold stress response crosstalk in apple.

Drought and cold stresses seriously affect tree growth and fruit yield during apple (Malus domestica) production, with combined stress causing injury such as shoot shriveling. However, the molecular mechanism underlying crosstalk between responses to drought and cold stress remains to be clarified. In this study, we characterized the zinc finger transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) through comparative analysis of shoot-shriveling tolerance between tolerant and sensitive apple rootstocks. MhZAT10 responded to both drought and cold stresses. Heterologous expression of MhZAT10 in the sensitive rootstock 'G935' from domesticated apple (Malus domestica) promoted shoot-shriveling tolerance, while silencing of MhZAT10 expression in the tolerant rootstock 'SH6' of Malus honanensis reduced stress tolerance. We determined that the apple transcription factor DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 2A (DREB2A) is a direct regulator activating the expression of MhZAT10 in response to drought stress. Apple plants overexpressing both MhDREB2A and MhZAT10 genes exhibited enhanced tolerance to drought and cold stress, while plants overexpressing MhDREB2A but with silenced expression of MhZAT10 showed reduced tolerance, suggesting a critical role of MhDREB2A-MhZAT10 in the crosstalk between drought and cold stress responses. We further identified drought-tolerant MhWRKY31 and cold-tolerant MhMYB88 and MhMYB124 as downstream regulatory target genes of MhZAT10. Our findings reveal a MhDREB2A-MhZAT10 module involved in crosstalk between drought and cold stress responses, which may have applications in apple rootstock breeding programs aimed at developing shoot-shriveling tolerance.

The lncRNA XIST/miR-150-5p/c-Fos axis regulates sepsis-induced myocardial injury via TXNIP-modulated pyroptosis.

Myocardial injury is a severe complication of sepsis and contributes substantially to the death of critically ill patients. Long non-coding RNAs (lncRNAs) participate in the pathogenesis of sepsis-induced myocardial injury. In this study, we investigated the role of lncRNA X-inactive specific transcript (XIST) in septic myocardial injury and explored its mechanism. Lipopolysaccharide (LPS)-stimulated H9C2 cells and rats subjected to cecal ligation and puncture (CLP) were used as the in vitro and in vivo models. After exposure to LPS, XIST and c-Fos levels were upregulated, but miR-150-5p was downregulated in H9C2 cardiomyocytes and myocardial tissues. XIST affected viability, apoptosis, and pyroptosis in LPS-challenged H9C2 cells. Moreover, XIST knockdown attenuated LPS-induced injury in H9C2 cells by targeting the miR-150-5p/c-Fos axis. c-Fos could bound to the promoter of the TXNIP/XIST gene and enhanced TXNIP/XIST expression. Silencing of XIST improved cardiac function and survival rate and reduced apoptosis and pyroptosis by regulating the miR-150-5p/c-Fos axis in septic rats in vivo. Taken together, our data show that XIST/miR-150-5p/c-Fos axis affected septic myocardial injury, which may indicate a novel therapeutic strategy for sepsis-induced myocardial injury.

In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China-Myanmar border of Yunnan Province, China from 2007 to 2013.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the recommended first-line treatment of falciparum malaria in all endemic countries. Artemisinin resistance in Plasmodium falciparum has been confirmed in the Greater Mekong subregion (GMS). Dihydroartemisinin-piperaquine (DAPQ) is the most commonly used ACT in China. To understand the DAPQ sensitivity of P. falciparum, DAPQ resistance was monitored in vivo along the China-Myanmar border from 2007 to 2013. METHODS: Eligible patients with mono-infections of P. falciparum were recruited to this study after obtaining full informed consent. DAPQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 42 days. Polymerase chain reaction (PCR) was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome was assessed according to the WHO recommended standards. RESULTS: 243 patients were completed valid follow-up. The fever clearance time (FCT) and asexual parasite clearance times (APCT) were, respectively, 36.5 ± 10.9 and 43.5 ± 11.8 hours, and there was an increasing trend of both FCT (F = 268.41, P < 0.0001) and APCT (F = 88.6, P < 0.0001) from 2007 to 2013. Eight (3.3%, 95% confidence interval, 1.4-6.4%) patients present parasitaemia on day three after medication; however they were spontaneous cure on day four. 241 (99.2%; 95% CI, 97.1-99.9%) of the patients were adequate clinical and parasitological response (ACPR) and the proportions of ACPR had not changed significantly from 2007 to 2013 (X(2) = 2.81, P = 0.7288). CONCLUSION: In terms of efficacy, DAPQ is still an effective treatment for falciparum malaria. DAPQ sensitivity in P. falciparum had not significantly changed along the China-Myanmar border of Yunnan Province, China. However more attentions should be given to becoming slower fever and parasite clearance.

[Preparation and optical properties of tantalum tungsten bronze].

Tantalum tungsten bronze(TaxWO3)nanowires were successfully synthesized via hydrothermal method using TaCl5 and Na2WO4 . 2H20 as raw materials. The morphology, crystal structure and optical properties of synthesized products were characterized by means of XRD, TEM, SEM, UV-Vis and Raman technologies. The XRD results showed that TaxWO3 nanowire exhibited hexagonal structure. By increasing the doping content, the cell parameter was kept increasing gradually till Ta/W= 0. 04, then it remained almost constant. The UV-Vis diffraction spectrum analysis showed that the absorption peaks redshifted, the band gap energy decreased with increasing the doping content. The Raman peaks moved with a downshift, and the peak gradually became broader, which further proved the influence of the tantalum doping for tungsten oxide. The reactions of decomposing liquid rhodamine B solution showed that the nanosized TaxWO3 had a high photo-catalytic activity.

Monitoring Plasmodium vivax chloroquine sensitivity along China-Myanmar border of Yunnan Province, China during 2008-2013.

BACKGROUND: Plasmodium vivax is the most widespread of the malaria parasites infecting human hosts. In malaria-eliminating settings, both imported and local malaria predominantly occurs in border areas, and most of them are P. vivax. Chloroquine (CQ) is the first-line drug for P. vivax treatment in China. To understand CQ sensitivity in P. vivax, in vivo monitoring of CQ resistance was conducted along the China-Myanmar border from 2008 to 2013. METHODS: Eligible patients with mono-infections of P. vivax were recruited to this study after obtaining full informed consent. CQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 28 days. PCR was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome and sensitivity were classified according to the WHO recommended standards. RESULTS: 603 patients were completed valid follow-up. The fever clearance time and asexual parasite clearance times were, respectively, 22.2 ± 10.2 and 38.1 ± 12.6 hours. 594 (98.5%) patients were adequate clinical and parasitological response (ACPR), and nine (1.5%) patients, who were late clinical failure (LCF) or resistant response level I (RI), were imported from the neighbouring districts of Myanmar. CONCLUSION: In terms of efficacy, CQ is still effective for vivax malaria treatment. Plasmodium vivax CQ sensitivity had not significantly changed along the China-Myanmar border of Yunnan Province, China.

The transcription factor MhZAT10 enhances antioxidant capacity by directly activating the antioxidant genes MhMSD1, MhAPX3a, and MhCAT1 in apple rootstock SH6 (Malus honanensis × M. domestica).

Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species (ROS) are eliminated upon activation of ZAT10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a), and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a, and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a, or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase, and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower ROS levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots, and antioxidant enzyme activity, as well as less ROS accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates ROS detoxification.

[Field evaluation of SD(BIOLINE) malaria antigen Plasmodium falciparum/Plasmodium vivax rapid test kit].

Four hundred and seventy-five patients with fever within 48 h were detected for Plasmodium using double blind field trials in China-Myanmar border from June to December 2011. The result showed that 202 of 475 were positive by SD(BIOLINE) kits, with 98 positive of Plasmodium falciparum and 104 positive of Plasmodium vivax. By microscope examination, 206 were positive. Taking the result of microscope examination as the reference standard, the general sensitivity and specificity were 98.1% (202/206) and 97.8% (263/269) respectively, and the general coincidence rate of SD(BIOLINE) kits with microscopy was 97.9% (465/475). The sensitivity and specificity of P. falciparum were 99.0% (98/99) and 97.8% (263/269) respectively, and the coincidence rate of SD(BIOLINE) with microscopy was 98.1% (361/368). The sensitivity and specificity of P. vivax were 97.2% (104/107) and 100% (269/269), and the coincidence rate of SD(BIOLINE) with microscopy was 99.2% (373/376). Therefore, the test results of SD(BIOLINE) are stable with a high specificity and sensitivity.

Nano-Sized Antioxidative Trimetallic Complex Based on Maillard Reaction Improves the Mineral Nutrients of Apple (Malus domestica Borkh.).

The metallic complex is widely used in agricultural applications. Due to the oxidation of the metal and environmental unfriendliness of ligand, maintaining an efficient mineral supply for plants without causing environmental damage is difficult. Herein, an antioxidative trimetallic complex with high stability was synthesized by interacting Ca2+, Fe2+, and Zn2+ with the biocompatible ligands from the Maillard reaction. The composite structure elucidation was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR). Thermal stability was measured by thermogravimetric (TG). Antioxidative activities were evaluated by ferric reducing antioxidant power and radical scavenging activity assays. The three metals were successfully fabricated on the Maillard reaction products (MRPs) with contents of Ca (9.01%), Fe (8.25%), and Zn (9.67%). Microscopy images revealed that the three metals were uniformly distributed on the MRPs with partial aggregation of <30 nm. FTIR and XPS results revealed that the metals were interacted with MRPs by metal-O and metal-N bonds. TG and antioxidative activity assays showed that the trimetallic complex meets the requirements of thermodynamics and oxidation resistance of horticultural applications. Additionally, the results of the exogenous spraying experiment showed that the trimetallic complex significantly increased the mineral contents of the "Fuji" apple. By treatment with the complex, the concentrations of Ca, Fe, and Zn were increased by 85.4, 532.5, and 931.1% in the leaf; 16.0, 225.2, and 468.6% in the peel; and 117.6, 217.9, and 19.5% in the flesh, respectively. The MRP-based complexes offered a higher growth rate of the mineral content in apples than ones based on sugars or amino acids. The results of the spraying experiment carried out in 2 years show that the method has high reproducibility. This study thus promotes the development of green metallic complexes and expands the scope of agrochemical strategy.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning.

BACKGROUND: The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning (AOPP). METHODS: In this retrospective cohort study, we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals. Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension. We also evaluated the association between clinical parameters (including hypotension) and in-hospital mortality. RESULTS: The incidence of hypotension in AOPP patients was 16.4%. Hypotensive patients showed significantly higher in-hospital mortality (1.1% vs. 39.9%, P<0.001). Advanced age (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.08-1.44), history of diabetes (OR 2.65, 95% CI 1.14-5.96), and increased white blood cell count (OR 1.06, 95% CI 1.03-1.09), plasma cholinesterase (OR 0.91, 95% CI 0.84-0.94), plasma albumin (OR 0.88, 95% CI 0.85-0.92), serum amylase (OR 1.01, 95% CI 1.01-1.02), and blood pH (OR 0.64, 95% CI 0.54-0.75) were significantly associated with hypotension. After adjusting for potential confounders, hypotension was associated with increased in-hospital mortality (hazard ratio 8.77-37.06, depending on the controlled variables). CONCLUSIONS: Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality. Advanced age, history of diabetes, and changes in laboratory parameters were associated with hypotension in AOPP patients.

A Novel Oncogenic Driver in a Lung Adenocarcinoma Patient Harboring an EGFR-KDD and Response to Afatinib.

Introduction: Oncogenic mutations in the epidermal growth factor receptor (EGFR) occur frequently in patients with lung cancer. These mutations may serve as critical predictive biomarkers in patients with non-small cell lung cancer (NSCLC). Among them, EGFR exon 18-25 kinase domain duplication (EGFR-KDD) mutations have been identified as a novel EGFR gene subtype in NSCLC. Case Presentation: We reported a rare case of a 59-year-old male diagnosed with adenocarcinoma. A biopsy revealed an EGFR-KDD identified by the next generation sequencing (NGS). Effective treatment outcome has been observed after administration with afatinib. Conclusion: This case highlights that comprehensive NGS technique is valuable in detecting novel genetic mutations in tumors.

Dual drive coexistence of ALK rearrangement and KRAS mutation advanced lung adenocarcinoma and response to crizotinib.

Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with epidermal growth factor receptor (EGFR) or KRAS mutations. Herein, we reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by an next-generation sequencing (NGS) assay. The patient had a favorable tumor response to crizotinib, a tyrosine kinase inhibitor (TKI). A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.

[Multivariate analysis of relationship between soil nutrient factors and fruit quality characte-ristic of 'Fuji' apple in two dominant production regions of China]. / 两大优势产区'富士'è‹¹æžœå›­åœŸå£¤å »åˆ†ä¸Žæžœå®žå“è´¨å ³ç³»çš„å¤šå˜é‡åˆ†æž.

The objective of this experiment is to probe into the influence of soil nutrient contents on fruit quality features of 'Fuji' apple, screen major soil nutrient factors affecting fruit quality features, clarify the suitable soil nutrient content for good fruit quality indicators, and to provide theoretical basis in reasonable orchard soil fertilizer application for improving fruit qua-lity in the Circum-Bohai and Loess Plateau apple production regions in China. The soil nutrient contents and 'Fuji' fruit qualities were respectively analyzed at 66 commercial 'Fuji' apple orchards standard rootstock in the Circum-Bohai and Loess Plateau apple production regions of 22 counties in China from 2010 to 2011. The partial least squares regression (PLS) was used to screen major soil nutrient elements affecting fruit quality, and to establish regression equation of relationship between fruit quality and major soil nutrition factors. Linear programming was used to obtain optimum proposals of soil nutrient elements for good apple quality. The results showed that alkaline hydrolytic N, available P, Ca, Fe, and Zn of soil were significantly higher while pH and available K were significantly lower in Circum-Bohai region than in Loess Plateau apple production region. Soluble solid content in Loess Plateau was higher than in Circum-Bohai; moreover, ratio of soluble solids content and titratable acidity was lower. The soil available B in the Circum-Bohai and Loess Plateau apple production regions had positive effect on fruit mass, and total N had negative effect on fruit firmness. The soluble solid contents in the Circum-Bohai were mainly negatively affected by total N and positively by available B, while positively affected by available Ca and negatively by alkaline hydrolytic N in the Loess Plateau region. The desired soil nutrients for good fruit qualities were high avai-lable B, pH and suitable available K in the Circum-Bohai, and low total N, high alkaline hydrolytic N, available K, Fe and suitable available Zn and B in the Loess Plateau region. It was the key technical measures in soil nutrient management for good fruit quality to increase available B and pH, adjust available K in the Circum-Bohai, and to enhance alkaline hydrolytic N, available K, Fe, and to decrease pH, and adjust available Zn and B in the Loess Plateau region.

Elevated serum ubiquitin C-terminal hydrolase-L1 levels in patients with carbon monoxide poisoning.

OBJECTIVE: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been established as a reliable and potential biomarker of neuronal damage after acute neurologic insults, such as ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. However, the effect of serum UCH-L1 levels has not been investigated in carbon monoxide (CO)-poisoned patients. The aim of the present study was to evaluate whether serum UCH-L1 levels are a reliable marker of brain damage and the association of UCH-L1 with outcome. DESIGN AND METHODS: This case-control study enrolled 46 CO-poisoned subjects and 30 controls. Using an enzyme-linked immunosorbent assay (ELISA) kit, we studied the temporal profile of serum UCH-L1 levels at 6, 12, 24 and 48 h after acute CO poisoning. Poisoning severity was assessed using the Glasgow Coma Scale (GCS) score. Long-term outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months after poisoning. RESULTS: Compared with controls, CO-poisoned patients had significantly elevated serum levels of UCH-L1 at each time point after poisoning. There were significantly higher levels of UCH-L1 in CO-poisoned patients with a lower GCS score as well as in those with a poor 6-month outcome dichotomized GOS. CONCLUSIONS: Serum levels of UCH-L1 appear to have potential clinical utility in providing valuable information about poisoning severity and outcome after CO poisoning.

TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion.

Histone deacetylases (HDACs) are important in chromatin remodeling and epigenetic regulation of gene expression. Histone deacetylase inhibitors (HDACi) have highly effective anti-metastatic and anti-angiogenic activity in various types of cancer, while the molecular mechanisms involved in this process are not fully understood. In the present study, trichostatin A (TSA), a HDACi, was found to suppress MCF-7 breast carcinoma cell invasion and upregulate TET1 expression in a dose-dependent manner. TET1, a dioxygenase involved in cytosine demethylation, is downregulated during breast cancer progression. TET1 knockdown in MCF-7 cells facilitates cell invasion, inhibits the expression of tissue inhibitors of metalloproteinase 2/3 (TIMP2/3) and promotes matrix metalloproteinases (MMP) 2/9 transcriptional activity. Importantly, TET1 depletion impaired the inhibitory effect of TSA on breast cancer cell invasion. Together, these results illustrated a mechanism by which TET1 partially mediates HDACi elicited suppression of breast cancer invasion.

Characterization of sck1, a novel Castanea mollissima mutant with the extreme short catkins and decreased gibberellin.

A novel Chinese chestnut (Castanea mollissima Bl.) mutant with extreme short catkins, here was named sck1 and has been characterized in the present study. This sck1 caused 6-fold shorter than wild-type catkins. Endogenous gibberellic acids markedly decreased in the mutant, and application of exogenous GA(3) could partially restore the sck1 phenotype to the wild-type phenotype. Paclobutrazol (PP(333)), an antagonist of GAs biosynthesis, could significantly inhibit the wild-type catkins growth, and lead to a short catkins phenotype similar to the sck1. In addition, compared to the wild-type catkins, the mRNA expression level of ent-kaurenoic acid oxidase (KAO), a gibberellin biosynthesis key gene, was significantly down-regulated (P<0.01) in the sck1. Importantly, transient over-expression of a normal CmKAO gene in short catkins also could partially restore the wild-type phenotype. Real-time PCR and semi-quantitative analysis showed that the mRNA expression level of KAO was significantly up-regulated. In addition, transient RNA interference of CmKAO in wild-type catkins led the mRNA expression level of KAO decrease significantly and inhibited the wild-type catkins elongation strongly. Taken together, our results suggest that the lower gibberellic acids content that is due to decreased CmKAO expression level may contribute to the generation of the extreme short male catkins, sck1.