Genetic dissection of grain morphology and yield components in a wheat line with defective grain filling.

KEY MESSAGE: We identified stable QTL for grain morphology and yield component traits in a wheat defective grain filling line and validated genetic effects in a panel of cultivars using breeding-relevant markers. Grain filling capacity is essential for grain yield and appearance quality in cereal crops. Identification of genetic loci for grain filling is important for wheat improvement. However, there are few genetic studies on grain filling in wheat. Here, a defective grain filling (DGF) line wdgf1 characterized by shrunken grains was identified in a population derived from multi-round crosses involving nine parents and a recombinant inbreed line (RIL) population was generated from the cross between wdgf1 and a sister line with normal grains. We constructed a genetic map of the RIL population using the wheat 15K single nucleotide polymorphism chip and detected 25 stable quantitative trait loci (QTL) for grain morphology and yield components, including three for DGF, eleven for grain size, six for thousand grain weight, three for grain number per spike and two for spike number per m2. Among them, QDGF.caas-7A is co-located with QTGW.caas-7A and can explain 39.4-64.6% of the phenotypic variances, indicating that this QTL is a major locus controlling DGF. Sequencing and linkage mapping showed that TaSus2-2B and Rht-B1 were candidate genes for QTGW.caas-2B and the QTL cluster (QTGW.caas-4B, QGNS.caas-4B, and QSN.caas-4B), respectively. We developed kompetitive allele-specific PCR markers tightly linked to the stable QTL without corresponding to known yield-related genes, and validated their genetic effects in a diverse panel of wheat cultivars. These findings not only lay a solid foundation for genetic dissection underlying grain filling and yield formation, but also provide useful tools for marker-assisted breeding.

Fine mapping and characterization of a major QTL for plant height on chromosome 5A in wheat.

KEY MESSAGE: We precisely mapped QPH.caas-5AL for plant height in wheat, predicted candidate genes and confirmed genetic effects in a panel of wheat cultivars. Plant height is an important agronomic trait, and appropriately reduced height can improve yield potential and stability in wheat, usually combined with sufficient water and fertilizer. We previously detected a stable major-effect quantitative trait locus QPH.caas-5AL for plant height on chromosome 5A in a recombinant inbred line population of the cross 'Doumai × Shi 4185' using the wheat 90 K SNP assay. Here , QPH.caas-5AL was confirmed using new phenotypic data in additional environment and new-developed markers. We identified nine heterozygous recombinant plants for fine mapping of QPH.caas-5AL and developed 14 breeder-friendly kompetitive allele-specific PCR markers in the region of QPH.caas-5AL based on the genome re-sequencing data of parents. Phenotyping and genotyping analyses of secondary populations derived from the self-pollinated heterozygous recombinant plants delimited QPH.caas-5AL into an approximate 3.0 Mb physical region (521.0-524.0 Mb) according to the Chinese Spring reference genome. This region contains 45 annotated genes, and six of them were predicted as the candidates of QPH.caas-5AL based on genome and transcriptome sequencing analyses. We further validated that QPH.caas-5AL has significant effects on plant height but not yield component traits in a diverse panel of wheat cultivars; its dwarfing allele is frequently used in modern wheat cultivars. These findings lay a solid foundation for the map-based cloning of QPH.caas-5AL and also provide a breeding-applicable tool for its marker-assisted selection. Keymessage We precisely mapped QPH.caas-5AL for plant height in wheat, predicted candidate genes and confirmed genetic effects in a panel of wheat cultivars.

Risk factors of elevated blood ammonia level in epilepsy patients treated with lamotrigine.

AbstractThe aim of this study was to explore the effect of lamotrigine (LTG) on blood ammonia level in patients with epilepsy and identify risk factors affecting blood ammonia level. This study included 91 epilepsy patients who were treated with LTG at Department of Neurology, Zhongshan Hospital, Xiamen University from January 2011 to April 2016, and were followed up for 3 years. Blood samples were taken during the interictal state and analyzed for blood LTG and ammonia levels. Total of 46.1% of the samples exceeded the median blood ammonia level, and 2.1% of patients had hyperammonemia. Blood ammonia level was positively correlated with LTG blood concentration. LTG combined with valproic acid therapy, seizure within 1 year, and elevated neutrophils affected blood ammonia level. Blood ammonia level was significantly correlated with plasma concentration of LTG. LTG combined with valproic acid therapy, seizure within 1 year, and elevated neutrophils may be risk factors for elevated blood ammonia level in epilepsy patients treated with LTG.

Preliminary Study on the Effect of Impaired Glucose Tolerance on Blood-Brain Barrier Permeability in Non-Neurosyphilis Patients.

Background: Blood-brain barrier (BBB) is frequently disrupted in patients with diabetes mellitus (DM) and/or neurosyphilis (NS). Clinical cases reflect a trend that non-neurosyphilis (non-NS) patients with impaired glucose tolerance (IGT) are likely to develop NS and/or DM. Objective: To investigate whether IGT promotes BBB disruption in patients with non-NS. Methods and Material: A total of 21 subjects were enrolled, including six with IGT, nine with non-NS, and six with both IGT and non-NS. BBB permeability was evaluated by dynamic contrast-enhanced (DCE) MRI and the secretion of biomarkers from cerebrospinal fluid (CSF) were measured by colorimetric method, immune turbidimetric method, and enzyme-linked immunosorbent assay (ELISA) method. Results: The non-NS patients with IGT have higher BBB permeability at cortex superior frontal gyrus, white matter, and thalamus than non-NS patients without IGT or IGT patients without non-NS. The CSF-serum albumin-quotient (Qalb) levels and CSF secretion are highest in non-NS patients with IGT, including matrix metalloproteinase 9 (MMP9), soluble intercellular cell adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1). Conclusions: Significant correlations between CSF biomarkers and BBB permeability were found.

Predictors of hemorrhagic complications after intravenous thrombolysis in acute cerebral infarction patients: A single-center study of 391 cases.

ABSTRACT: For patients with ischemic stroke, intravenous (IV) thrombolysis with Urokinase within 6 hours has been accepted as beneficial, but its application is limited by high risk of hemorrhagic complications after thrombolysis. This study aimed to analyze the risk factors of hemorrhagic complications after intravenous thrombolysis using Urokinase in acute cerebral infarction (ACI) patients.Total 391 consecutive ACI patients were enrolled and divided into 2 groups: the hemorrhagic complications group and the non-hemorrhagic complications group. The related data were collected and analyzed.Univariate analysis showed significant differences in prothrombin time, atrial fibrillation (AF), Mean platelet volume, large platelet ratio (L-PLR), triglyceride (TG), Lactate dehydrogenase, alanine aminotransferase (ALT), high-density lipoprotein, and baseline National Institute of Health Stroke Scale score between the hemorrhagic complications and the non-hemorrhagic complications group (P < .1). Multivariate logistic regression analysis indicated that AF (odds ratio [OR] = 2.91, 95% confidence interval [CI] = 1.06-7.99 P = .039) was the risk factor of hemorrhagic complications, while ALT (OR = 0.27, 95% CI = 0.10-0.72 P = .009) and TG (OR = 0.16, 95% CI = 0.06-0.45 P = .000) were protective factors of hemorrhagic complications.For patients with AF and lower levels of ALT or TG, the risk of hemorrhagic complications might increase after ACI.

Fine mapping and validation of a major QTL for grain weight on chromosome 5B in bread wheat.

KEY MESSAGE: A major QTL QTgw.caas-5B for thousand grain weight in wheat was fine mapped on chromosome 5B, and TraesCS5B02G044800 was predicted to be the candidate gene. Thousand grain weight (TGW), determined by grain length and width, and is an important yield component in wheat; understanding of the underlying genes and molecular mechanisms remains limited. A stable QTL QTgw.caas-5B for TGW was identified previously in a RIL population developed from a cross between Zhongmai 871 (ZM871) and a sister line Zhongmai 895 (ZM895), and the aim of this study was to perform fine mapping and validate the genetic effect of the QTL. It was delimited to an interval of approximately 2.0 Mb flanked by markers Kasp_5B29 and Kasp_5B31 (49.6-51.6 Mb) using 12 heterozygous recombinant plants obtained by selfing a residual BC1F6 line selected from the ZM871/ZM895//ZM871 population. A candidate gene was predicted following sequencing and differential expression analyses. Marker Kasp_5B_Tgw based on a SNP in TraesCS5B02G044800, the QTgw.caas-5B candidate, was developed and validated in a diversity panel of 166 cultivars. The precise mapping of QTgw.caas-5B laid a foundation for cloning of a predicted causal gene and provides a molecular marker for improving grain yield in wheat.

Predictors of Outcome in Juvenile Myoclonic Epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome, accounting for 10% of all epilepsy. However, there is limited information regarding the predictors of seizure outcome. The aim of this study was to determine the predictors of seizure outcome in JME patients. METHODS: A population-based retrospective study of JME patients who were treated at the Department of Neurology of affiliated Zhongshan Hospital, Xiamen University from 2008 to 2013. RESULTS: Sixty-three patients (30 women and 33 men) were enrolled in this study. The median age at seizure onset was 14 years old, and the average duration of epilepsy was 5 years. The onset of JME at age <16 years was found in 63.5% of patients. The epileptiform runs ≥3 s were observed in 35.8% patients. Febrile seizure was noted in 28.9% of patients. Among 63 patients, 40 patients (63.5%) had remission. Multivariate analysis identified the following factors as significant predictors of seizure outcome: the onset of JME at age <16 years, epileptiform runs ≥3 s runs, and febrile seizure. CONCLUSION: The onset of JME at age <16 years, febrile seizures and epileptiform runs ≥3 s might be associated with poor long-term seizure outcome in patients with JME.

Influencing Factors of Recanalization after Intravenous Thrombolysis with Urokinase in Acute Cerebral Infarction Patients.

BACKGROUND: Intravenous thrombolysis (IVT) with urokinase is the standard reperfusion therapy for acute cerebral infarction (ACI) in China. Only about 30% patients who use urokinase for IVT can recanalize. Therefore, this study aimed to analyze the influencing factors of recanalization after IVT using urokinase in ACI patients. METHODS: A total of 391 consecutive patients with a diagnosis of ACI from January 2013 to October 2019 were enrolled and divided into 2 groups: patients without recanalization and patients with recanalization. Related data were collected and analyzed. RESULTS: Univariate analysis showed that there were significant differences in gender, atrial fibrillation, erythrocyte mean corpuscular volume, platelet large cell ratio (P-LCR), glucose (GLU), and severity of ICAS between patients without recanalization and patients with recanalization (p < 0.05). Multivariate logistic regression analysis indicated that P-LCR (odds ratio [OR] = 0.17, 95% confidence interval [CI] = 0.03-0.89, p = 0.04), GLU (OR = 0.28, 95% CI = 0.11-0.67, p = 0.004), and ICAS severity (OR = 0.48, 95% CI = 0.32-0.76, p = 0.001) were the influencing factors of recanalization. CONCLUSION: For patients with higher levels of P-LCR, GLU, or ICAS severity, the recanalization rate might decrease after ACI.

High HbA1c level is correlated with blood-brain barrier disruption in syphilis patients.

Diabetes mellitus (DM) and neurosyphilis (NS) may both damage the blood-brain barrier (BBB). It seems that non-neurosyphilis (non-NS) patients with high HbA1c levels are likely to develop into NS. However, the correlation of HbA1c level with BBB disruption in syphilis (non-NS) patients is unclear. In this study, we used dynamic contrast-enhanced (DCE) MRI to quantify regional BBB permeability in syphilis (non-NS) patients and detected several molecular biomarkers of cerebrospinal fluid (CSF). We found that BBB permeability values in the hippocampus, white matter, and cortex inferior temporal gyrus were correlated with albumin quotient (Qalb), CSF concentrations of interleukin IL-6 and IL-10. Moreover, BBB breakdown in white matter was correlated with CSF concentrations of sICAM-1 and sVCAM-1. In conclusion, our data suggest that BBB integrity may be liable to be disrupted in syphilis (non-NS) patients, patients with high HbA1c levels, as well as syphilis (non-NS) patients with high HbA1c levels, and it is particularly important to control blood glucose in these patients.

Pleiotrophin regulates functional heterogeneity of microglia cells in EAE animal models of multiple sclerosis by activating CCr-7/CD206 molecules and functional cytokines.

Multiple sclerosis (MS) is a neurodegenerative and immune-mediated disorder that characterizes by demyelination and neuro-inflammation. This study aimed to investigate the effects of pleiotrophin (PTN) on treatment of early injuries of white matter of MS patients. Experimental autoimmune encephalomyelitis (EAE) animal models were established by injecting 200 µg myelinoligodendrocyte glyeoprotein 33-35 (MOG35-55) and were divided into PTN+MOG group and PBS+MOG group. Meanwhile, normal mice group was assigned as control group (NC group). Immunofluorescence double label was used to examined co-expression of molecules. LV5-PTN and LV3-siPTN were established and transfected into microglia cells. All brain imaging data was acquired with MRI scanner. Quantitative real-time RT-PCR (qRT-PCR) and western blot were used to evaluate mRNA and protein expression, respectively. Lesion sites mainly appeared in NAWM of bilateral occipital lobes in EAE models. PTN treatment significantly enhanced CCr7 and reduced CD206 expression compared to PBS+MOG group (P<0.05). PTN participated in mitogen-activated protein kinase (MAPK) signaling pathway in EAE models. PTN treatment significantly regulated levels of functional cytokines in both M1 and M2 type microglia cells compared to PBS+MOG group (P<0.05). LV5-PTN and LV3-siPTN transfection modulated levels of PTN and MAPK molecule in microglia cells undergoing treatment of M1 or M2 inducer. PTN strengthened M1/M2 transformation by regulating functional cytokines. In conclusion, PTN regulated functional heterogeneity of microglia cells in EAE animal models of MS by activating CCr-7/CD206 molecules and functional cytokines. PTN could be considered as a promising candidate molecule for treating early injuries of white matter of patients with MS.