A novel dual-activatable fluorescence/MRI bimodal platform is designed for tumor cell imaging by using a redoxable manganese dioxide (MnO2) nanosheet-aptamer nanoprobe. The redoxable MnO2 nanosheet acts as a DNA nanocarrier, fluorescence quencher, and intracellular glutathione (GSH)-activated MRI contrast agent. In the absence of target cells, neither fluorescence signaling nor MRI contrast of the nanoprobe is activated. In the presence of target cells, the binding of aptamers to their targets weakens the adsorption of aptamers on the MnO2 nanosheets, causing partial fluorescence recovery, illuminating the target cells, and also facilitating the endocytosis of nanoprobes into target cells. After endocytosis, the reduction of MnO2 nanosheets by GSH further activates the fluorescence signals and generates large amounts of Mn(2+) ions suitable for MRI. This platform should facilitate the development of various dual-activatable fluorescence/MRI bimodalities for use in cells or in vivo.
The mating system transition in polyploid Brassica napus (AACC) from out-crossing to selfing is a typical trait to differentiate it from their diploid progenitors. Elucidating the mechanism of mating system transition has profound consequences for understanding the speciation and evolution in B. napus. Functional complementation experiment has shown that the insertion of 3.6 kb into the promoter of self-incompatibility male determining gene, BnSP11-1 leads to its loss of function in B. napus. The inserted fragment was found to be a non-autonomous Helitron transposon. Further analysis showed that the inserted 3.6 kb non-autonomous Helitron transposon was widely distributed in B. napus accessions which contain the S haplotype BnS-1. Through promoter deletion analysis, an enhancer and a putative cis-regulatory element (TTCTA) that were required for spatio-temporal specific expression of BnSP11-1 were identified, and both might be disrupted by the insertion of Helitron transposon. We suggested that the insertion of Helitron transposons in the promoter of BnSP11-1 gene had altered the mating system and might facilitated the speciation of B. napus. Our findings have profound consequences for understanding the self-compatibility in B. napus as well as for the trait variations during evolutionary process of plant polyploidization.
Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre-and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain-perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain-related GM and WM Youming Zhang and Minli Qu contributed equally to this work.
Self-incompatibility (SI) is a widespread mechanism in angiosperms that prevents inbreeding by rejecting self-pollen. However, the regulation of the SI response in Brassica napus is not well understood. Here, we report that the M-locus protein kinase (MLPK) BnaMLPKs, the functional homolog of BrMLPKs in Brassica rapa, controls SI in B. napus. We identified four paralogue MLPK genes in B. napus, including BnaA3.MLPK, BnaC3.MLPK, BnaA4.MLPK, and BnaC4.MLPK. Two transcripts of BnaA3.MLPK, BnaA3.MLPKf1 and BnaA3.MLPKf2, were generated by alternative splicing. Tissue expression pattern analysis demonstrated that BnaA3.MLPK, especially BnaA3.MLPKf2, is highly expressed in reproductive organs, particularly in stigmas. We subsequently created RNA-silencing lines and CRISPR/Cas9-induced quadruple mutants of BnaMLPKs in B. napus SI line S-70. Phenotypic analysis revealed that SI response is partially suppressed in RNA-silencing lines and is completely blocked in quadruple mutants. These results indicate the importance of BnaMLPKs in regulating the SI response of B. napus. We found that the expression of SI positive regulators S-locus receptor kinase (SRK) and Arm-Repeat Containing 1 (ARC1) are suppressed in bnmlpk mutant, whereas the self-compatibility (SC) element Glyoxalase I (GLO1) maintained a high expression level. Overall, our findings reveal a new regulatory mechanism of MLPK in the SI of B. napus.
Previous studies have suggested that resting-state functional connectivity plays a central role in the physiopathology of major depressive disorder (MDD). However, the individualized diagnosis of MDD based on resting-state functional connectivity is still unclear, especially in first episode drug-naive patients with MDD. Resting state functional magnetic resonance imaging was enrolled from 30 first episode drug-naive patients with MDD and age- and gender-matched 31 healthy controls. Whole brain functional connectivity was computed and viewed as classification features. Multivariate pattern analysis (MVPA) was performed to discriminate patients with MDD from controls. The experimental results exhibited a correct classification rate of 82.25% (p < 0.001) with sensitivity of 83.87% and specificity of 80.64%. Almost all of the consensus connections (125/128) were cross-network interaction among default mode network (DMN), salience network (SN), central executive network (CEN), visual cortex network (VN), Cerebellum and Other. Moreover, the supramarginal gyrus exhibited high discriminative power in classification. Our findings suggested cross-network interaction can be used as an effective biomarker for MDD clinical diagnosis, which may reveal the potential pathological mechanism for major depression. The current study further confirmed reliable application of MVPA in discriminating MDD patients from healthy controls.
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