Osa-miR1873 fine-tunes rice immunity against Magnaporthe oryzae and yield traits.

MicroRNAs (miRNAs) are known to fine-tune growth, development, and stress-induced responses. Osa-miR1873 is a rice-specific miRNA targeting LOC_Os05g01790. Here, we show that Osa-miR1873 fine-tunes rice immunity against Magnaporthe oryzae and yield traits via LOC_Os05g01790. Osa-miR1873 was significantly upregulated in a susceptible accession but downregulated in a resistance accession at 24 h post-inoculation (hpi) of M. oryzae. Overexpressing Osa-miR1873 enhanced susceptibility to M. oryzae and compromised induction of defense responses. In contrast, blocking Osa-miR1873 through target mimicry compromised susceptibility to M. oryzae and enhanced induction of defense responses. Altered expression of Osa-miR1873 also resulted in some defects in yield traits, including grain numbers and seed setting rate. Moreover, overexpression of the target gene LOC_Os05g01790 increased rice blast disease resistance but severely penalized growth and yield. Taken together, we demonstrate that Osa-miR1873 fine-tunes the rice immunity-growth trade-off via LOC_Os05g01790, and blocking Osa-miR1873 could improve blast disease resistance without significant yield penalty. Thus, the Osa-miR1873-LOC_Os05g01790 regulatory module is valuable in balancing yield traits and blast resistance.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review.

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Clinical and MRI features about two types of silent cerebral small-vessel disease in type-2 diabetes mellitus: a retrospective cross-sectional study in a tertiary hospital.

Background: The present study aimed to evaluate the frequency of silent cerebral small-vessel disease, especially lacunes and white matter hyperintensities, in patients with or without the impaired glucose tolerance (IGT) and type-2 diabetes mellitus, and to characterize the diabetes-correlated factors related to silent cerebral small-vessel disease. Methods: This is a retrospective cross-sectional study. Totally 698 patients were included in this study, from January 2014 to December 2019, among which 270 patients were included in the diabetes mellitus group, 106 patients were included in the IGT group, and 322 patients were included in the Control group. All patients underwent magnetic resonance imaging to investigate the silent cerebral small-vessel disease: the lacunes and the white matter hyperintensities. All the baseline information and diabetes-related factors, such as glycated hemoglobin level, insulin usage, etc., were collected. Then correlation analysis and regression analysis were used to explore the correlation between diabetes with related risk factors and silent cerebral small-vessel disease. Results: Lacunes and white matter hyperintensities were more common in the diabetes mellitus group than in the IGT group and the Control group, with an occurrence of lacunes of 83.3% vs. 70.8% vs. 70.4% (P=0.003), respectively, and an occurrence of white matter hyperintensities of 41.1% vs. 24.5% vs. 31.1% (P=0.003), respectively. The occurrence of lacunes was correlated with the duration of diabetes mellitus [odds ratio (OR) =1.483, 95% confidence interval (CI): 1.082-2.031, P=0.009] and the age (OR =1.141, 95% CI: 1.102-1.180, P<0.001), while white matter hyperintensities were independently correlated only with the age (OR =1.124, 95% CI: 1.094-1.155, P<0.001). Conclusions: Lacunes and white matter hyperintensities, are more common in the diabetes mellitus patients than in the IGT patients or in the other patients. The occurrence of lacunes was correlated with the duration of diabetes mellitus and the age, while the occurrence of white matter hyperintensities was independently correlated with the age.

Blocking miR530 Improves Rice Resistance, Yield, and Maturity.

MicroRNAs fine-tune plant growth and resistance against multiple biotic and abiotic stresses. The trade-off between biomass and resistance can penalize crop yield. In this study, we have shown that rice miR530 regulates blast disease resistance, yield, and growth period. While the overexpression of miR530 results in compromised blast disease resistance, reduced grain yield, and late maturity, blocking miR530 using a target mimic (MIM530) leads to enhanced resistance, increased grain yield, and early maturity. Further study revealed that the accumulation of miR530 was decreased in both leaves and panicles along with the increase of age. Such expression patterns were accordant with the enhanced resistance from seedlings to adult plants, and the grain development from panicle formation to fully-filled seeds. Divergence analysis of miR530 precursor with upstream 1,000-bp promoter sequence in 11 rice species revealed that miR530 was diverse in Oryza sativa japonica and O. sativa indica group, which was consistent with the different accumulation of miR530 in japonica accessions and indica accessions. Altogether, our results indicate that miR530 coordinates rice resistance, yield, and maturity, thus providing a potential regulatory module for breeding programs aiming to improve yield and disease resistance.

Expressing a Target Mimic of miR156fhl-3p Enhances Rice Blast Disease Resistance Without Yield Penalty by Improving SPL14 Expression.

MicroRNAs (miRNAs) play essential roles in the regulation of plant growth and defense responses. More and more, miRNA-3ps are reported to act in plant development and immunity. miR156 is a conserved miRNA, and most previous studies focus on its roles in plant growth, development, and yield determinacy. Here, we show that expressing a target mimic of miR156fhl-3p led to enhanced rice blast disease resistance without a yield penalty. miR156fhl-3p was differentially responsive to Magnaporthe oryzae in susceptible and resistant accessions. Transgenic lines expressing a target mimic of miR156fhl-3p (MIM156-3p) exhibited enhanced rice blast disease resistance and increased expression of defense-related genes. MIM156-3p also enhanced the mRNA abundance of SPL14 and WRKY45 by down-regulating miR156-5p and pre-miR156. Moreover, MIM156-3p lines displayed a decreased number of second rachis branches per panicle but enlarged grains, leading to unchanged yield per plant. Consistently, overexpressing miR156h (OX156) led to enhanced susceptibility to M. oryzae and decreased the expression of SPL14 and WRKY45. Our results indicate that miR156fhl-3p mounts a regulatory role on miR156-5p, which subsequently regulates the expression of SPL14 and WRKY45 to improve rice blast disease resistance.

Total flavones of Rhododendron simsii Planch flower protect isolated rat heart from ischaemia-reperfusion injury and its mechanism of UTR-RhoA-ROCK pathway inhibition.

OBJECTIVES: Total flavones of Rhododendron simsii Planch flower (TFR) are an effective part extracted from the flower. The present study was designed to investigate the protective effect of TFR in isolated rat heart following global ischaemia-reperfusion and the possible underlying mechanisms. METHODS: Langendorff perfusion apparatus was used to perfuse isolated rat heart which was subjected to global ischaemia-reperfusion. The hemodynamic parameters were continuously monitored. Coronary flow as well as lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB) and cardiac troponin I (cTnI) in coronary effluents was measured. RhoA activity and urotensin receptor (UTR) and Rho-related coiled-coil-forming protein kinase (ROCK) protein expressions in rat myocardium were examined, respectively. Cardiac dysfunction was indicated by the alterations of hemodynamic parameters and the reduced coronary flow. KEY FINDINGS: Total flavones of Rhododendron simsii Planch flower significantly improved ischaemia-reperfusion-induced cardiac dysfunction and leakages of LDH, CK-MB and cTnI, and inhibited myocardial ischaemia-reperfusion-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. The improvement of TFR in the cardiac dysfunction and the leakage of LDH, CK-MB and cTnI were markedly attenuated under the UTR blockade and ROCK inhibition. TFR-inhibited RhoA activity was decreased under the UTR blockade. CONCLUSIONS: Total flavones of Rhododendron simsii Planch flower had a protective effect on ischaemia-reperfusion injury in isolated rat heart, which may be attributed to the blocking of UTR and subsequent inhibition of the RhoA-ROCK pathway.