Phospholipidase Dδ Negatively Regulates the Function of Resistance to Pseudomonas syringae pv. Maculicola 1 (RPM1)

RPM1 is a plant immune receptor that specially recognizes pathogen-released effectors to activate effector-triggered immunity (ETI) in Arabidopsis thaliana. RPM1 triggers ETI and hypersensitive response (HR) for disease resistance. Previous reports indicated that Phospholipase D (PLD) positively regulated RPM1-mediated HR. However, single, double, and triple pld knock-out mutants of 12 members of the PLD family in A. thaliana did not show suppressed RPM1-mediated HR, indicating the functional redundancy among PLD members. In this study, we revealed that PLD could negatively regulate the function of RPM1. We found that RPM1 interacted with PLDδ, but did not interact with PLDβ1, PLDβ2, and PLDγ3. Overexpression of PLDδ conducted to a reduction of protein level and corresponding activity of RPM1. We found that abscisic acid (ABA) reduced the protein level of RPM1, and the ABA-induced RPM1 reduction required PLD activity and PLD-derived phosphatidic acid (PA). Our study shows that PLD plays both negative and positive roles regulating the protein level and activity of RPM1 during stress responses in plants. PLD proteins are regulating points to integrate the abiotic and biotic responses of plants

The IRE1α/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease

Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. ER stress is linked to inflammatory bowel disease (IBD). Here, we used cell culture, mouse models, and human specimens to determine whether ER stress in ILC3s affects IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24-hour rhythmic expression pattern of the master ER stress response regulator inositol-requiring kinase 1α/X-box-binding protein 1 (IRE1α/XBP1). Proinflammatory cytokine IL-23 selectively stimulated IRE1α/XBP1 in mouse ILC3s through mitochondrial ROS (mtROS). IRE1α/XBP1 was activated in ILC3s from mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1α deletion in ILC3s (Ire1αΔRorc) showed reduced expression of the ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal XBP1s+ ILC3s in patients with Crohn\u27s disease before administration of ustekinumab, an anti-IL-12/IL-23 antibody, positively correlated with the response to treatment. We demonstrate that a noncanonical mtROS-IRE1α/XBP1 pathway augmented cytokine production by ILC3s and identify XBP1s+ ILC3s as a potential biomarker for predicting the response to anti-IL-23 therapies in IBD

Characterization of a major quantitative trait locus on chromosome five for hundred-kernel weight of maize (Zea mays L)

Kernel weight is one of the most important components of grain yield and is controlled by quantitative trait loci (QTLs) derived from natural variations in maize. However, the molecular roles of QTLs in the regulation of kernel weight have not been fully elucidated. In this study, by using homozygous chromosome single segment substitu- tion lines Z22(SSSL-Z22) as base material, two F populations derived from a cross between elite maize inbred line Zheng58 and SSSL-Z22, were employed to map QTLs of kernel weight traits in two years at the same location. Out of four traits, 3 QTLs were detected in one of the two environments whereas 2 detected in both environments. Two major QTLs, qhkw5-3 for hundred-kernel weight and qkw5-3 for kernel width, were consistently detected in similar chromosome segment in different years. qhkw5-3 was mapped to Bin 5.06 flanked by the SSR markers SYM033 and SYM108 with a genetic interval of 8.8 cM, which made kernel size smaller. qkw5-3 was identified between SYM024 and SYM129 with a genetic interval of 13.9 cM. These results will help to promote the fine map- ping and cloning of the target gene and further develop linked markers to be used in marker-assisted breeding

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery

Purpose: The aim of this study was to build a population pharmacokinetics (PopPK) model of nalbuphine and to estimate the suitability of bodyweight or fixed dosage regimen.Method: Adult patients who were undergoing general anesthetic surgery using nalbuphine for induction of anesthesia were included. Plasma concentrations and covariates information were analyzed by non-linear mixed-effects modeling approach. Goodness-of-fit (GOF), non-parametric bootstrap, visual predictive check (VPC) and external evaluation were applied for the final PopPK model evaluation. Monte Carlo simulation was conducted to assess impact of covariates and dosage regimens on the plasma concentration to nalbuphine.Results: 47 patients aged 21–78 years with a body weight of 48–86 kg were included in the study. Among them, liver resection accounted for 14.8%, cholecystectomy for 12.8%, pancreatic resection for 36.2% and other surgeries for 36.2%. 353 samples from 27 patients were enrolled in model building group; 100 samples from 20 patients were enrolled in external validation group. The results of model evaluation showed that the pharmacokinetics of nalbuphine was adequately described by a two-compartment model. The hourly net fluid volume infused (HNF) was identified as a significant covariate about the intercompartmental clearance (Q) of nalbuphine with objective function value (OFV) decreasing by 9.643 (p < 0.005, df = 1). Simulation results demonstrated no need to adjust dosage based on HNF, and the biases of two dosage methods were less than 6%. The fixed dosage regimen had lower PK variability than the bodyweight regimen.Conclusion: A two-compartment PopPK model adequately described the concentration profile of nalbuphine intravenous injection for anesthesia induction. While HNF can affect the Q of nalbuphine, the magnitude of the effect was limited. Dosage adjustment based on HNF was not recommended. Furthermore, fixed dosage regimen might be better than body weight dosage regimen

Elevated homocysteine levels, white matter abnormalities and cognitive impairment in patients with late-life depression

BackgroundCognitive impairment in late−life depression (LLD) is considered to be caused by neurodegenerative changes. Elevated homocysteine (Hcy) levels may be linked to cognitive abnormalities associated with LLD. The important role of white matter (WM) damage in cognitive impairment and pathogenesis in patients with LLD has been widely reported. However, no research has explored the interrelationships of these features in patients with LLD.ObjectiveThe goal of the study was to examine the interrelationship between Hcy levels, cognition, and variations in WM microstructure detected by diffusion tensor imaging (DTI) in patients with LLD.MethodsWe recruited 89 healthy controls (HCs) and 113 patients with LLD; then, we measured the plasma Hcy levels of participants in both groups. All individuals performed a battery of neuropsychological tests to measure cognitive ability. Seventy-four patients with LLD and 68 HCs experienced a DTI magnetic resonance imaging (MRI) scan.ResultsPatients with LLD showed significantly lower fractional anisotropy (FA) values in the bilateral inferior longitudinal fasciculus than those of healthy participants. Only in LLD patients was Hcy concentration inversely associated to FA values in the forceps minor. Finally, multiple regression analyses showed that an interaction between Hcy levels and FA values in the right cingulum of the cingulate cortex and right inferior longitudinal fasciculus were independent contributors to the executive function of patients with LLD.ConclusionOur results highlight the complex interplay between elevated homocysteine levels and WM abnormalities in the pathophysiology of LLD-related cognitive impairment, consistent with the neurodegeneration hypothesis

Total Phenolics and Anthocyanins Contents and Antioxidant Activity in Four Different Aerial Parts of Leafy Sweet Potato (Ipomoea batatas L.)

Leafy sweet potato (Ipomoea batatas L.) is an excellent source of nutritious greens and natural antioxidants, but reports on antioxidants content and activity at buds, leaves, petioles, and stems are scarce. Therefore, the total phenolics content (TPC), total anthocyanins content (TAC), and antioxidant activity (assessed by DPPH and ABTS radical scavenging activities and ferric reducing antioxidant power (FRAP)) were investigated in four aerial parts of 11 leafy sweet potato varieties. The results showed that varieties with pure green aerial parts, independently of the part analyzed, had higher TPC, FRAP, and ABTS radical scavenging activities. The green-purple varieties had a significantly higher TAC, while variety GS-17-22 had the highest TAC in apical buds and leaves, and variety Ziyang in petioles and stems. Among all parts, apical buds presented the highest TPC and antioxidant capacity, followed by leaves, petioles, and stems, while the highest TAC level was detected in leaves. The TPC was positively correlated with ABTS radical scavenging activity and FRAP in all parts studied, whereas the TAC was negatively correlated with DPPH radical scavenging activity. Collectively, the apical buds and leaves of sweet potato had the higher levels of nutritional values. These results would provide reference values for further breeding of leafy sweet potatoes