Phosphatases maintain low catalytic activity of SGK1: DNA damage resets the balance in favor of phosphorylation.

The serum- and glucocorticoid-induced kinase 1 (SGK1) promotes cell survival under stress conditions and facilitates the emergence of drug resistance in cancer. The underlying mechanisms of these observations are not fully understood. In this study, we found that SGK1 activity is suppressed by the action of the S/T phosphatases PP5 and PP2A, which constantly dephosphorylate SGK1. Using newly developed anti-phospho SGK1 antibodies and inhibitors of phosphatases, we determined that the high degree of dephosphorylation is caused by two factors: the tendency of SGK1 to unfold, which makes it dependent on Hsp90 chaperone complexes composed of four proteins, Hsp90/CDC37/PP5/SGK1, and where the phosphatase PP5 persistently dephosphorylates SGK1 within the complex. SGK1 binding to PP2A regulatory subunits B55γ and B55δ brings PP2A catalytic subunit close to exposed SGK1 phosphoresidues. A further association of phosphorylated pS37-FAM122A-an endogenous inhibitor of PP2A-to the holoenzyme diminishes dephosphorylation of SGK1 mediated by PP2A. Our study also reveals that genotoxic stress can reverse the dominant impact of phosphatases over kinases by activating the DNA-dependent protein kinase, which enhances mTORC2 activity directed to SGK1. Thus, our results provide insight into a molecular pathway that enables SGK1 to gain phosphorylation and catalytic activity and promote cell survival, potentially diminishing the efficacy of cancer treatments. As the DNA damage response operates in many cancer cells and is further induced by chemotherapies, the findings of this study could have significant implications for the development of novel cancer therapies targeting SGK1.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.

MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis.

BACKGROUND: Endothelial cell disturbance underpins a role in pathogenesis of atherosclerosis. Notably, accumulating studies indicate the substantial role of microRNAs (miRs) in atherosclerosis, and miR-199a-5p dysregulation has been associated with atherosclerosis and other cardiovascular disorders. However, the effect of miR-199a-5p on the phenotypes of endothelial cells and atherosclerosis remains largely unknown. METHODS: ApoE-/- male mice were fed with high-fat diet for detection of inflammation and aorta plaque area. Extracellular vesicles (EVs) were separated from THP-1-derived macrophage (THP-1-DM) that was treated by oxidized low-density lipoprotein, followed by co-culture with human aortic endothelial cells (HAECs). Ectopic expression and downregulation of miR-199a-5p were done in THP-1-DM-derived EVs to assess pyroptosis and lactate dehydrogenase (LDH) of HAECs. Binding relationship between miR-199a-5p and SMARCA4 was evaluated by luciferase activity assay. RESULTS: EVs derived from ox-LDL-induced THP-1-DM expedited inflammation and aorta plaque area in atherosclerotic mice. Besides, miR-199a-5p expression was reduced in EVs from ox-LDL-induced THP-1-DM, and miR-199a-5p inhibition facilitated HAEC pyroptosis and LDH activity. Moreover, miR-199a-5p targeted and restricted SMARCA4, and then SMARCA4 activated the NF-κB pathway by increasing PODXL expression in HAECs. CONCLUSION: EV-packaged inhibited miR-199a-5p from macrophages expedites endothelial cell pyroptosis and further accelerates atherosclerosis through the SMARCA4/PODXL/NF-κB axis, providing promising targets and strategies for the prevention and treatment of atherosclerosis.

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides.

Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.

miR169o and ZmNF-YA13 act in concert to coordinate the expression of ZmYUC1 that determines seed size and weight in maize kernels.

MicroRNAs (miRNAs) play key regulatory roles in seed development and emerge as new key targets for engineering grain size and yield. The Zma-miRNA169 family is highly expressed during maize seed development, but its functional roles in seed development remain elusive. Here, we generated zma-miR169o and ZmNF-YA13 transgenic plants. Phenotypic and genetic analyses were performed on these lines. Seed development and auxins contents were investigated. Overexpression of maize miRNA zma-miR169o increases seed size and weight, whereas the opposite is true when its expression is suppressed. Further studies revealed that zma-miR169 acts by negatively regulating its target gene, a transcription factor ZmNF-YA13 that also plays a key role in determining seed size. We demonstrate that ZmNF-YA13 regulates the expression of the auxin biosynthetic gene ZmYUC1, which modulates auxin levels in the early developing seeds and determines the number of endosperm cells, thereby governing maize seed size and ultimately yield. Overall, our present study has identified zma-miR169o and ZmNF-YA13 that form a functional module regulating auxin accumulation in maize seeds and playing an important role in determining maize seed size and yield, providing a set of novel molecular tools for yield improvement in molecular breeding and genetic engineering.

The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states.

BACKGROUND: Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous. METHODS: A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan-Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states. RESULTS: MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan-Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07-1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17-1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13-1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14-1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05). CONCLUSIONS: Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.

ONOO- -mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells.

Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low-grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO- )-mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC-ECM), which was obtained by deoxycholate (DOC)-based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO- -mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO- was found in the serum of AS mice, and ONOO- could stimulate the development of AS. SMC-ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO- -mediated oxidization destroyed the three-dimensional structure of SMC-ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation- and oxidative stress-related genes was significantly increased in ECM subjected to ONOO- -mediated oxidization, thereby contributing to AS progression. ONOO- -mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs.

Association between serum pyrethroid insecticide levels and incident type 2 diabetes risk: a nested case-control study in Dongfeng-Tongji cohort.

Pyrethroid insecticides have been extensively used worldwide, but few studies explored the prospective association between pyrethroid exposure and incident type 2 diabetes (T2D). We conducted a nested case-control study of 2012 paired cases and controls, and measured eight pyrethroid insecticides in the baseline sera. We used conditional logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals, and constructed multiple-pollutant models to investigate the association of pyrethroid mixture with incident T2D risk. The median concentrations (detection rates) were 3.53 µg/L (92.45%), 0.52 µg/L (99.80%), 1.16 µg/L (90.61%) and 1.43 µg/L (99.95%) for permethrin, cypermethrin, fenvalerate, and deltamethrin, respectively. Compared to participants with serum fenvalerate levels in the first quartile, the multivariable-adjusted ORs of incident T2D were 1.20 (95% CI 0.86-1.67), 1.41 (0.97-2.05), and 2.29 (1.27-4.11) for the second, third and fourth quartile (P trend = 0.01). Spline analysis further confirmed the positive association between serum fenvalerate levels and incident T2D risk (P for overall association = 0.006). Furthermore, mixture models revealed a positive association of pyrethroid mixture with incident T2D risk, with serum fenvalerate ranked as the top contributor (proportion of relative contribution: > 70%). We found that high concentrations of serum pyrethroid insecticides were significantly associated with an increased risk of incident T2D. The elevated risk was largely explained by fenvalerate. Further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms, given the widespread use of pyrethroids and the global pandemic of diabetes.

The effects of extracellular vesicles derived from Krüppel-Like Factor 2 overexpressing endothelial cells on the regulation of cardiac inflammation in the dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear. METHODS AND RESULTS: EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6high Mo/Mø in the myocardium. We used flow cytometry to detect Ly6high monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6Chigh monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C-C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow. CONCLUSIONS: EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6Chigh monocyte mobilization from the bone marrow.

Short-term and long-term outcomes of bailout versus planned coronary rotational atherectomy.

The goal of this study was to compare in-hospital and long-term events between bailout rotational atherectomy (RA) and planned RA. In this retrospective study, All patients who underwent percutaneous coronary intervention (PCI) using RA at Nanjing Drum Tower Hospital from November 2011 to December 2018 were enrolled in this study. Planned RA was defined as RA performed immediately before balloon pre-dilation, while bailout RA was defined as RA after failure to expand the balloon or perform any other procedure. In-hospital and long-term major adverse cardiac events (MACE, defined as cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR) and stroke) were compared between the two groups. After statistical analysis, a total of 211 patients underwent PCI with RA during the study period: 153 in the planned RA group, and 58 in the bailout group. The incidence of coronary dissection was significantly higher in the bailout RA group than in the planned RA group (22.4% vs. 6.5%, P = 0.001). However, no significant difference in in-hospital MACE was found between the two groups (12.1% vs. 13.7%, P = 0.752). There was no difference in all-cause mortality (9.1% vs. 12.5%, P = 0.504) or long-term MACE (13.8% vs. 17.1%, P = 0.560) between the groups. Bailout RA was associated with a significantly longer procedural time (139.86 ± 56.24 min vs. 105.56 ± 36.71 min, P < 0.001) than planned RA. Therefore, compared with bailout RA, planned RA is associated with shorter procedural time and reduced incidence of coronary dissection, with no difference in MACE or mortality.

Comparison of the prognosis for different onset stage of cardiogenic shock secondary to ST-segment elevation myocardial infarction.

OBJECTIVES: The study was conducted to evaluate the outcomes of different onset stage of cardiogenic shock (CS) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Total 675 STEMI patients who had undergone primary percutaneous coronary intervention (pPCI) from November 2010 to December 2017 in Nanjing Drum Tower Hospital were enrolled. According to the onset time of CS, the cohort was divided into three groups: Non-CS group, CS on admission group and Developed CS group. The short-term (30 days), middle-term (12 months) and long-term (80 months) outcomes were analyzed. COX proportional hazard models were established for identification of the predictors. RESULTS: The all cause death, cardiac death and major adverse cardiac events (MACE) at 30 days were similar among the three groups. The incidence of MACE in the CS on admission group was significantly higher than the other two groups at 12 months. As to the long-term outcomes, the CS on admission group had lower survival rate than the other two groups. The Develop CS group had lower survival rate than Non-CS group numerically with a trend towards statistical significance. The incidence of cardiac death in the Non-CS group was the lowest. The incidence of MACE in the CS on admission group was much higher compared with the other two groups. After multivariate analysis, the independent predictors of all cause death included age, male sex, prior stroke and LVEF. The independent predictors of cardiac death included age, male sex, prior stroke, LVEF, CS on admission and developed CS. The independent predictors of MACE included age, prior stroke, LVEF, multivessel lesions, post-PCI TIMI grade 1 and CS on admission. CONCLUSIONS: The long-term outcomes of CS on admission group were the worst of all. The outcomes of Developed CS group laid between the other two groups. The consequences highlighted the importance of prevention for CS developing in the STEMI patients during hospitalization.

MCR Approach Revealing Protein, Water, and Lipid Depth Profile in Atopic Dermatitis Patients' Stratum Corneum via in Vivo Confocal Raman Spectroscopy.

Confocal Raman has been widely used for measuring the water concentration profile inside skin to calculate clinical end points, such as stratum corneum thickness. In this article, multivariate curve resolution was applied to resolve the pure components contained in high frequency (2500-4000 cm-1) in vivo confocal Raman data. Three components were identified by comparing with reference spectra of materials in skin. These three components are water, protein, and lipid. The score values associated with these three components were transformed to mass ratio by leveraging the response factors for protein and lipid in a calibration model utilizing the pure material spectra. The concentration profiles for protein and lipid as a function of depth across the stratum corneum are utilized as new clinical end points. Results from an in vivo study with individuals who experience atopic dermatitis symptoms successfully demonstrated a statistical difference between Raman spectra from nonlesion and lesion skin sites. Trends in the depth profiles of the skin components are consistent with previous literature reports.

Circular RNA circ-FOXM1 facilitates cell progression as ceRNA to target PPDPF and MACC1 by sponging miR-1304-5p in non-small cell lung cancer.

Circular RNAs (circRNAs) have recently been considered as key regulators in carcinogenesis. Nevertheless, the study of circRNAs involved in non-small cell lung cancer (NSCLC) remains largely unclear. In this study, we aim to explore the clinical significance, regulatory effect and mechanism of circ-FOXM1 in NSCLC. The results indicated that circ-FOXM1 overexpression was observed in NSCLC tissues and closely associated with lymph node invasion, higher TNM stage, and unfavorable prognosis. Furthermore, knockdown and ectopic expression of circ-FOXM1 significantly inhibited and promoted the growth, migration and invasion of NSCLC cells, respectively. Mechanistically, miR-1304-5p was discovered as a direct target of circ-FOXM1. Circ-FOXM1 upregulated the level of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and metastasis-associated in colon cancer 1 (MACC1) by sponging miR-1304-5p, thereby increasing the proliferation and invasion of NSCLC cells. Taken together, this work revealed that circ-FOXM1/miR-1304-5p/PPDPF/MACC1 signaling was essential for the development and progression of NSCLC.

Accessory gene regulator (agr) dysfunction was unusual in Staphylococcus aureus isolated from Chinese children.

BACKGROUND: Staphylococcus aureus (S. aureus) with accessory gene regulator (agr) dysfunction occurs in health care settings. This study evaluated the prevalence and the molecular and drug resistance characteristics of S. aureus with dysfunctional agr in a pediatric population in Beijing, China. RESULTS: A total of 269 nonduplicate S. aureus clinical isolates were isolated from Beijing Children's Hospital, including 211 methicillin-resistant S. aureus (MRSA) from September 2010-2017 and 58 methicillin-sensitive S. aureus (MSSA) from February 2016-2017. Only 8 MRSA and 2 MSSA isolates were identified as agr dysfunction, and the overall prevalence rate was 3.7%. For MRSA isolates, ST59-SCCmec IV and ST239-SCCmec III were the most common clones, and the prevalence rate of agr dysfunction in ST239-SCCmec III isolates (17.39%) was significantly higher than in ST59-SCCmec IV (1.69%) and other genotype strains (P = 0.006). Among the agr dysfunctional isolates, only one MRSA ST59 isolate and one MSSA ST22 isolate harbored pvl. No significant difference was detected between agr dysfunction and agr functional isolates regarding the biofilm formation ability (P = 0.4972); however, 9/10 agr dysfunctional isolates could effectuate strong biofilm formation and multidrug resistance. Among MRSA, the non-susceptibility rates to ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole were significantly higher in agr dysfunctional isolates than in isolates with functional agr (P < 0.05). Two isolates belonging to ST239 had no mutations in agr locus, but a synonymous mutation was found in agrA in another ST239 isolate. The inactivating mutations were detected in other seven agr dysfunctional isolates. The variants were characterized by non-synonymous changes (n = 5) and frameshift mutations (insertions, n = 2), which mainly occurred in agrC and agrA. CONCLUSIONS: The results showed that agr dysfunctional S. aureus was not common in Chinese children, and ST59-SCCmec IV was associated with lower prevalence of agr dysfunction as compared to ST239-SCCmec III isolates. The agr dysfunctional isolates were healthcare-associated, multidrug resistant and form strong biofilm, which suggested that agr dysfunction might offer potential advantages for S. aureus to survive in a medical environment.

Seasonal variations of tris (2-chloroethyl) phosphate and cytotoxicity of organic extracts in water samples from Wuhan, China.

Tris (2-chloroethyl) phosphate (TCEP) is a typical phosphate flame retardant. Its potential adverse health effects have recently aroused concern. We investigated the seasonal variations of TCEP concentrations in the raw, finished and tap water samples from two drinking water treatment plants (DWTPs) in China, and evaluated the cytotoxicity and apoptosis/necrosis of organic extracts (OEs) in water samples. We enriched TCEP and OEs in water samples by solid-phase extraction method. The TCEP concentrations in water samples were determined by gas chromatography-mass spectrometry. Normal human liver cell line L02 was treated with OEs in the water samples, and then the cytotoxicity and apoptosis/necrosis were measured by 3-(4, 5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and flow cytometry, respectively. The results showed that cytotoxicities of OEs in raw water samples from both DWTPs in summer and winter were stronger than those in spring and autumn, cytotoxicity of OEs in finished and tap water samples from both DWTPs in summer and autumn were stronger than those in spring and winter. In all seasons, the maximal concentrations (100 mL water/mL cell culture) of OEs in the raw water samples from both DWTPs induced late apoptosis/necrosis. The reasons for seasonal variations of TCEP in water samples and potential toxic effects of other pollutants in the water samples need to be further investigated.

Aberrant Meiotic Modulation Partially Contributes to the Lower Germination Rate of Pollen Grains in Maize (Zea mays L.) Under Low Nitrogen Supply.

Pollen germination is an essential step towards successful pollination during maize reproduction. How low niutrogen (N) affects pollen germination remains an interesting biological question to be addressed. We found that only low N resulted in a significantly lower germination rate of pollen grains after 4 weeks of low N, phosphorus or potassium treatment in maize production. Importantly, cytological analysis showed 7-fold more micronuclei in male meiocytes under the low N treatment than in the control, indicating that the lower germination rate of pollen grains was partially due to numerous chromosome loss events resulting from preceding meiosis. The appearance of 10 bivalents in the control and low N cells at diakinesis suggested that chromosome pairing and recombination in meiosis I was not affected by low N. Further gene expression analysis revealed dramatic down-regulation of Nuclear Division Cycle 80 (Ndc80) and Regulator of Chromosome Condensation 1 (Rcc1-1) expression and up-regulation of Cell Division Cycle 20 (Cdc20-1) expression, although no significant difference in the expression level of kinetochore foundation proteins Centromeric Histone H3 (Cenh3) and Centromere Protein C (Cenpc) and cohesion regulators Recombination 8 (Rec8) and Shugoshin (Sgo1) was observed. Aberrant modulation of three key meiotic regulators presumably resulted in a high likelihood of erroneous chromosome segregation, as testified by pronounced lagging chromosomes at anaphase I or cell cycle disruption at meiosis II. Thus, we proposed a cytogenetic mechanism whereby low N affects male meiosis and causes a higher chromosome loss frequency and eventually a lower germination rate of pollen grains in a staple crop plant.

Multiresistant ST59-SCCmec IV-t437 clone with strong biofilm-forming capacity was identified predominantly in MRSA isolated from Chinese children.

BACKGROUND: This study aimed to investigate the clinical and molecular epidemiology and biofilm formation of Staphylococcus aureus (SA) isolated from pediatricians in China. METHODS: SA strains were isolated from Beijing Children's hospital from February 2016 to January 2017. Isolates were typed by multilocus sequence typing (MLST), spa and SCCmec typing (for Methicillin-resistant SA [MRSA] only). Antimicrobial susceptibility testing was performed by agar dilution method except sulphamethoxazole/trimethoprim (E-test method). Biofilm formation and biofilm associated genes were detected. RESULTS: Totally 104 children (41 females and 63 males; median age, 5.2 months) were enrolled in this study, in which 60 patients suffered from MRSA infection. Among the 104 cases, 54.8% were categorized as community associated SA (CA-SA) infections. The children under 3 years were more likely to occur CA-SA infections compared with older ones (P = 0.0131). ST59-SCCmec IV-t437 (61.7%) was the most prevalent genotype of MRSA, and ST22-t309 (18.2%), ST5-t002 (9.1%), ST6-t701 (9.1%), ST188-t189 (9.1%) were the top four genotypes of methicillin-sensitive SA (MSSA). All the present isolates were susceptible to linezolid, vancomycin, trimethoprim-sulfamethoxazole, mupirocin, tigecyclin, fusidic acid. No erythromycin-susceptible isolate was determined, and only a few isolates (3.8%) were identified as susceptible to penicillin. Multi-drug resistant isolates were reponsible for 83.8% of the ST59-SCCmec IV-t437 isolates. The isolates with strong biofilm formation were found in 85% of MRSA and 53.2% of MSSA, and in 88.7% of ST59-SCCmec IV-t437 isolates. Biofilm formation ability varied not only between MRSA and MSSA (P = 0.0053), but also greatly among different genotypes (P < 0.0001). The prevalence of the biofilm associated genes among ST59-SCCmec IV-t437 clone was: icaA (100.0%), icaD (97.3%), fnbpA (100.0%), fnbpB (0), clfA (100%), clfB (100%), cna (2.7%), bbp (0), ebpS (88.5%), sdrC (78.4%), sdrD (5.4%), and sdrE (94.5%). CONCLUSIONS: These results indicated strong homology of the MRSA stains isolated from Chinese children, which was caused by spread of multiresistant ST59-SCCmec IV-t437 clone with strong biofilm formation ability. The MSSA strains, in contrast, were very heterogeneity, half of which could produce biofilm strongly.

ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase mediating shoot branching.

MAIN CONCLUSION: ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase that may mediate strigolactone biosynthesis highly responsive to phosphorus deficiency and undergoes negative selection over domestication from Zea ssp. parviglumis to Zea mays. Carotenoid cleavage dioxygenase 7 (CCD7) functions to suppress shoot branching by controlling strigolactone biosynthesis. However, little is known about CCD7 and its functions in maize and its ancestor (Zea ssp. parviglumis) with numerous shoot branches. We found that ZmCCD7 and ZpCCD7 had the same coding sequence, indicating negative selection of the CCD7 gene over domestication from Zea ssp. parviglumis to Zea mays. CCD7 expression was highly responsive to phosphorus deficiency in both species, especially in the meristematic zone and the pericycle of the elongation zone of maize roots. Notably, the crown root had the strongest ZmCCD7 expression in the meristematic zone under phosphorus limitation. Transient expression of GFP tagged ZmCCD7/ZpCCD7 in maize protoplasts indicated their localization in the plastid. Further, ZmCCD7/ZpCCD7 efficiently catalyzed metabolism of six different linear and cyclic carotenoids in E. coli, and generated ß-ionone by cleaving ß-carotene at the 9,10 (9',10') position. Together with suppression of shoot branching in the max3 mutant by transformation of ZmCCD7/ZpCCD7, our work suggested that ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase mediating strigolactone biosynthesis in maize and its ancestor.

Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway.

Tris(2-chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP-induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP-induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd.

ZD958 is a low-nitrogen-efficient maize hybrid at the seedling stage among five maize and two teosinte lines.

MAIN CONCLUSION: ZD958 was the most low-N-efficient line among five maize and two teosinte lines. Zea parviglumis and Zea diploperennis were insensitive to N limitation. Maize and teosinte genetically and evolutionarily diverged in gene regulation. GDH2, ASN2, and T4 were consistently down-regulated across seven lines. Maternal asymmetric inheritance and heterosis vigor made ZD958 low-N-efficient. Nitrogen (N) deficiency remains a serious limiting factor for maize production in many developing countries. It is particularly important to better understand how hybrid maize responds to N limitation. ZD958, a dominant high-yield hybrid in North China, was comparatively analyzed with four other maize and two teosinte lines at physiological and transcriptional levels. ZD958 was the most low-N-efficient line among five maize and two teosinte lines due to its largest biomass accumulation at a lowest N concentration under N limitation; while Zea parviglumis and Zea diploperennis had large root systems and were insensitive to N limitation. In anti-parallel with down-regulation of N metabolic genes in the ZD958 root, carbon allocation towards the root was enhanced for the significant increase in the root length. Variations in expression patterns of ten genes mediating N uptake, transport, and metabolism indicated large genetic and evolutionary divergence among seven lines under N limitation. Notably, GDH2, ASN2, and VAAT5 were consistently down-regulated under N limitation across these maize and teosinte lines, suggesting essential evolutionary conservation of gene regulation in response to N limitation and providing molecular markers for N nutritional diagnosis. Asymmetric inheritance, mostly from its maternal donor Z58, and heterosis vigor made ZD958 low-N-efficient at the seedling stage. The superior traits in crown roots in ZD958 may be derived from its paternal donor Chang7-2. Thus, Z58, Chang7-2, and two wild maize lines (Z. parviglumis and Z. diploperennis) provide valuable germplasms for N-efficient and large-root maize breeding.