Unraveling wheat's response to salt stress during early growth stages through transcriptomic analysis and co-expression network profiling.

BACKGROUND: Soil salinization is one of the vital factors threatening the world's food security. To reveal the biological mechanism of response to salt stress in wheat, this study was conducted to resolve the transcription level difference to salt stress between CM6005 (salt-tolerant) and KN9204 (salt-sensitive) at the germination and seedling stage. RESULTS: To investigate the molecular mechanism underlying salt tolerance in wheat, we conducted comprehensive transcriptome analyses at the seedling and germination stages. Two wheat cultivars, CM6005 (salt-tolerant) and KN9204 (salt-sensitive) were subjected to salt treatment, resulting in a total of 24 transcriptomes. Through expression-network analysis, we identified 17 modules, 16 and 13 of which highly correlate with salt tolerance-related phenotypes in the germination and seedling stages, respectively. Moreover, we identified candidate Hub genes associated with specific modules and explored their regulatory relationships using co-expression data. Enrichment analysis revealed specific enrichment of gibberellin-related terms and pathways in CM6005, highlighting the potential importance of gibberellin regulation in enhancing salt tolerance. In contrast, KN9204 exhibited specific enrichment in glutathione-related terms and activities, suggesting the involvement of glutathione-mediated antioxidant mechanisms in conferring resistance to salt stress. Additionally, glucose transport was found to be a fundamental mechanism for salt tolerance during wheat seedling and germination stages, indicating its potential universality in wheat. Wheat plants improve their resilience and productivity by utilizing adaptive mechanisms like adjusting osmotic balance, bolstering antioxidant defenses, accumulating compatible solutes, altering root morphology, and regulating hormones, enabling them to better withstand extended periods of salt stress. CONCLUSION: Through utilizing transcriptome-level analysis employing WGCNA, we have revealed a potential regulatory mechanism that governs the response to salt stress and recovery in wheat cultivars. Furthermore, we have identified key candidate central genes that play a crucial role in this mechanism. These central genes are likely to be vital components within the gene expression network associated with salt tolerance. The findings of this study strongly support the molecular breeding of salt-tolerant wheat, particularly by utilizing the genetic advancements based on CM6005 and KN9204.

Subgenome-biased expression and functional diversification of a Na+/H+ antiporter homoeologs in salt tolerance of polyploid wheat.

Common wheat (Triticum aestivum, BBAADD) is an allohexaploid species combines the D genome from Ae. tauschii and with the AB genomes from tetraploid wheat (Triticum turgidum). Compared with tetraploid wheat, hexaploid wheat has wide-ranging adaptability to environmental adversity such as salt stress. However, little is known about the molecular basis underlying this trait. The plasma membrane Na+/H+ transporter Salt Overly Sensitive 1 (SOS1) is a key determinant of salt tolerance in plants. Here we show that the upregulation of TaSOS1 expression is positively correlated with salt tolerance variation in polyploid wheat. Furthermore, both transcriptional analysis and GUS staining on transgenic plants indicated TaSOS1-A and TaSOS1-B exhibited higher basal expression in roots and leaves in normal conditions and further up-regulated under salt stress; while TaSOS1-D showed markedly lower expression in roots and leaves under normal conditions, but significant up-regulated in roots but not leaves under salt stress. Moreover, transgenic studies in Arabidopsis demonstrate that three TaSOS1 homoeologs display different contribution to salt tolerance and TaSOS1-D plays the prominent role in salt stress. Our findings provide insights into the subgenomic homoeologs variation potential to broad adaptability of natural polyploidy wheat, which might effective for genetic improvement of salinity tolerance in wheat and other crops.

Comparison of the prevalence and nature of potentially inappropriate medication use in geriatric outpatients between tertiary and community healthcare settings: a multicenter cross-sectional study.

Background Geriatric outpatients with polypharmacy have a high risk of potentially inappropriate medication (PIM) use. Aim To identify differences in both prevalence and patterns of PIMs and drug-related problems (DRPs) in older outpatients who visited the tertiary hospitals (THs) and community health centers (CHCs) and analyze associated factors. Method A prospective cross-sectional study was conducted in five THs and five CHCs from September 2018 to November 2019 in Beijing, China. Data were collected from outpatients aged ≥ 65 years with chronic diseases and polypharmacy. PIMs were evaluated using the 2015 and 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) criteria. DRPs were classified using the Helper-Strand DRP Classification. The prevalence and types of PIMs and DRPs were compared, and relevant factors were analyzed. Results The prevalence of PIMs based on the 2015 Beers Criteria was higher in patients from the THs, while PIMs based on the 2019 Beers Criteria did not show a significant difference. PIM prevalence based on STOPP Criteria and DRPs was higher in patients from CHCs. Visiting CHCs was an independent factor of PIMs based on the 2015 Beers Criteria (OR 0.774, 95% CI 0.604-0.992) and the STOPP Criteria (OR 2.427, 95% CI 1.883-3.128), and DRPs (OR 3.612, 95% CI 2.682-4.865). Conclusion Differences in PIM and DRP might be due to the patients and settings. Specific measures to improve the appropriateness of medications in both settings should be used.

Function analysis of proteins encoded by ORFs 1 to 8 of porcine circovirus-like virus P1 by microarray assay.

Porcine circovirus-like agent P1 is a newly discovered virus containing a single-strand circular genome. The genome of P1 is a DNA molecule of 648 nucleotides which contains eight open reading frames (ORFs) that probably encode potential proteins or polypeptides. Thus it is very important to clarify these proteins' function. Here we provide the methods and analysis of microarray data in detail to characterize the transcriptome profile of P1 with and without the ORF. The relevant microarray data sets have been deposited in Gene Expression Omnibus (GEO) database under accession number GSE71945.

Association of serum levels of intercellular adhesion molecule-1 and interleukin-6 with migraine.

To investigate the associations of serum levels of intercellular adhesion molecule-1 (ICAM1) and the pro-inflammatory cytokine interleukin-6 (IL-6) with migraine and migraine subtypes, and to study their correlation with each other in this condition. We used enzyme-linked immunosorbent assay to measure serum levels of ICAM1 and IL-6 in 103 migraine patients with and without aura, in both attack and pain-free periods, and in 100 healthy control subjects. Serum levels of ICAM1 and IL-6 were significantly higher in migraine patients during attacks than in controls (p < 0.05). Serum ICAM1 levels were significantly higher in migraine with aura (MA) than in migraine without aura (MO), (p < 0.05). Correlation analysis indicated a significant positive correlation between serum levels of ICAM1 and IL-6 (p < 0.05) in migraine patients during attacks. Our results indicate that ICAM1 and IL-6 are involved in the pathogenesis of migraine attacks, possibly via an interactive mechanism.

Prenatal exposure to organophosphate pesticides and neurobehavioral development of neonates: a birth cohort study in Shenyang, China.

BACKGROUND: A large amount of organophosphate pesticides (OPs) are used in agriculture in China every year, contributing to exposure of OPs through dietary consumption among the general population. However, the level of exposure to OPs in China is still uncertain. OBJECTIVE: To investigate the effect of the exposure to OPs on the neonatal neurodevelopment during pregnancy in Shenyang, China. METHODS: 249 pregnant women enrolled in the Central Hospital Affiliated to Shenyang Medical College from February 2011 to August 2012. A cohort of the mothers and their neonates participated in the study and information on each subject was obtained by questionnaire. Dialkyl phosphate (DAP) metabolites were detected in the urine of mothers during pregnancy to evaluate the exposure level to OPs. Neonate neurobehavioral developmental levels were assessed according to the standards of the Neonatal Behavioral Neurological Assessment (NBNA). Multiple linear regressions were utilized to analyze the association between pregnancy exposure to OPs and neonatal neurobehavioral development. RESULTS: The geometric means (GM) of urinary metabolites for dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP), diethyl phosphate (DEP), and diethyl thiophosphate (DETP) in pregnant women were 18.03, 8.53, 7.14, and 5.64 µg/L, respectively. Results from multiple linear regressions showed that prenatal OP exposure was one of the most important factors affecting NBNA scores. Prenatal total DAP concentrations were inversely associated with scores on the NBNA scales.?Additionally, a 10-fold increase in DAP concentrations was associated with a decrease of 1.78 regarding the Summary NBNA (95% CI, -2.12 to -1.45). And there was an estimated 2.11-point difference in summary NBNA scores between neonates in the highest quintile of prenatal OP exposure and the lowest quintile group. CONCLUSION: The high exposure of pregnant women to OPs in Shenyang, China was the predominant risk factor for neonatal neurobehavioral development.

[Epidemiological study on developmental delay of 18-month-old children from four districts/counties in Beijing].

OBJECTIVE: To investigate epidemiological characteristics of prevalence, impact factors and etiology on developmental delay of 18-month-old children from four districts/counties in Beijing. METHODS: An epidemiological study on developmental delay was designed to investigate all the 18-month-old children enrolled from Shunyi,Daxing,Miyun and Yanqing districts/counties in Beijing from May to September, 2011. Combining the tertiary network of child health with hospital clinical study was used. Child developmental questionnaires were completed by doctors in communities of the first network of child health. Gesell Developmental Schedules for children with Denver developmental screening test (DDST) screening positive results were assessed by doctors in districts/counties hospitals of the second network of child health. The children diagnosed as developmental delay were transferred to the tertiary hospitals of the third network of child health for further etiological diagnosis, follow-up and developmental evaluation. The case-control study compared between children with/without developmental delay were performed in accordance with the 1:4 ratios by gender and residence community matched. SPSS 16.0 was adopted for data analysis of the case-control study. RESULTS: A total of 3 182 children were screened among the 4 037 children fitting the criteria,and the coverage rate was 78.8% (3 182/4 037). Of the 3 182 screened children, 22 children were diagnosed as developmental delay. The prevalence rate was 6.91 ‰ (22/3 182). Out of the 22 children with developmental delay, 15 were boys and 7 were girls. The sex ratio was 2.1:1. The prevalence rates of the children with developmental delay in Shunyi, Daxing, Miyun and Yanqing were 3.45 ‰ (4/1 160), 4.50 ‰(5/1 111), 15.87 ‰(7/441) and 12.77 ‰ (6/479), respectively. The results from one-way ANOVA analysis showed the main risk factors in children with developmental delay included low-income families, mothers' low educational level, small size for gestational age infant, multiple fetuses, serious diseases after birth, congenital malformations and physical retardation (P<0.05). CONCLUSION: The screening coverage rate of this study is 78.8%. The prevalence rate of children with developmental delay is 6.91 ‰, which is significantly different in sex ratio and districts of the subjects. The etiology of developmental delay might be associated with social-economic and biological factors.

Recombinant human growth hormone secreted from tissue-engineered bioartificial muscle improves left ventricular function in rat with acute myocardial infarction.

BACKGROUND: Experimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF. METHODS: Primary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n = 6) and CHF treatment group (n = 6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n = 6) and sham treatment group (n = 6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed. hGH, insulin-like growth factor-1 (IGF-1) and TNF-alpha levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry. RESULTS: Primary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 microg of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction (EF) and fractional shortening (FS) were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs ((65.0 +/- 6.5)% vs (48.1 +/- 6.8)%, P < 0.05), ((41.3 +/- 7.4)% vs (26.5 +/- 7.1)%, P < 0.05). LV end-diastolic dimension (LVEDD) was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM (P < 0.05). The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-alpha decreased more significantly in the CHF treatment group than in the CHF control group. CONCLUSIONS: rhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.

[Recombinant human growth hormone promotes in vitro mesenchymal stem cell growth].

OBJECTIVE: To detect the effect of recombinant human growth hormone (rhGH) to mesenchymal stem cells (MSCs) in vitro. METHODS: Various concentrations of rhGH (terminal concentrations 1, 10, 50, 100, 200 and 500 microg/L) were added to medium containing the second generation of MSCs, A value was measured by MTT method at various concentrations and at 24, 48 and 72 h. The expression of insulin-like growth factor 1(IGF-1) mRNA in the presence (24, 48 and 72 h) or absence (the 4(th) day, the 9(th) day, the 10(th) day, the 2(nd) week, the 3(rd) week and the 4(th) week post removal of rhGH) of various rhGH concentrations was determined by RT-PCR. RESULTS: rhGH could promote the MSCs growth at concentration > 10 microg/L in a time-dependent manner. The optimal concentration was 200 microg/L with a growth rate 144.74%. The expression of IGF-1 mRNA increased in a time-dependent manner gradually (0.6749 +/- 0.0084, 0.7781 +/- 0.0068, 0.8230 +/- 0.0060 at 24, 48 and 72 h, respectively at 200 microg/L rhGH). After rhGH withdraw, the expression of IGF-1 mRNA decreased in a time-dependent manner till 2 weeks (0.5287 +/- 0.0077, 0.5747 +/- 0.0050, 0.6068 +/- 0.0056, 0.7071 +/- 0.0089, 0.5791 +/- 0.0057, 0.5781 +/- 0.0081 at the 4(th) day, the 9(th) day, the 10(th) day, the 2(nd) week, the 3(rd) week and the 4(th) week post removal of rhGH). CONCLUSION: rhGH could promote the growth of MSCs in vitro.

[Therapeutic effects of recombinant human growth hormone and mesenchymal stem cells transplantation alone or in combination in adriamycin induced cardiomyopathy rat model].

OBJECTIVE: To investigate the therapeutic effects of recombinant human growth hormone (rhGH) and mesenchymal stem cells (MSCs) transplantation alone or in combination in adriamycin-induced cardiomyopathy (CM) rat model. METHODS: Wistar rats were divided into normal (n = 6), CM (n = 9), rhGH (2 mg/kg, subcutaneous injection, qod for 1 month, n = 6), MSCs transplantation (MSCs group, 5 x 10(6)/100 microl, n = 7) and rhGH + MSCs (G + M group, n = 7) groups. After 1 month, hemodynamic data, the ratio of heart weight/body weight (HW/BW) and left ventricular weight/body weight (LW/BW) were obtained. The myocardial MSCs marked by BrdU were detected by immunohistochemistry. Cardiac myosin heavy-chain (MHC) and its isozymes were detected by SDS-PAGE technique. Serum growth hormone (GH) and B-type natriuretic peptide (BNP) levels were measured. RESULTS: Compared to CM group, cardiac function remained unchanged in MSC group while significantly improved in rhGH group and further improved in G + M group. HW/BW and LW/BW were similar among groups (all P > 0.05). The MSCs number in the myocardium of G + M group was significantly higher than those of MSCs group. Compared to CM group, V3-MHC was significantly increased in MSCs group (10.33 +/- 0.33 vs 7.43 +/- 2.08, P < 0.05), V1 and V3-MHC were significantly increased in G + M group (86.22 +/- 1.73 vs 77.47 +/- 2.02, 12.44 +/- 0.31 vs 7.43 +/- 2.08, all P < 0.05). GH levels were significantly higher in rhGH and G + M treated animals than that in CM animals [(2.50 +/- 0.68) vs (1.37 +/- 0.09) microg/L, (2.48 +/- 0.90) vs (1.25 +/- 0.42) microg/L, all P < 0.05], BNP levels were significantly lower in rhGH, MSCs and G + M treated groups than that in CM group [(1270.72 +/- 203.72) vs (1462.44 +/- 242.87) ng/L, (1385.00 +/- 250.13) vs ( 1475.29 +/- 281.33) ng/L, (1219.31 +/- 126.71) vs (1451.78 +/- 180.93) ng/L, all P < 0.05]. CONCLUSIONS: rhGH but not MSC could improve the cardiac function in adriamycin-induced CM rats. Combined rhGH and MSCs transplantation therapy could further improve cardiac function possibly due to enhanced MSCs growth and transformation into cardiomyocytes.