The role of non-coding RNAs in neuropathic pain.

Neuropathic pain (NPP) is a refractory pain syndrome, caused by damage or disease of the somatosensory nervous system and characterized by spontaneous pain, hyperalgesia, abnormal pain and sensory abnormality. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and Piwi interacting RNA (piRNA), play a notable role in initiation and maintenance of NPP. In this review, we summarize the role of ncRNAs in NPP and their underlaying mechanism. Generally, ncRNAs are interacted with mRNA, protein or DNA to regulate the molecules and signals assciated with neuroinflammation, ion channels, neurotrophic factors and others, and then involved in the occurrence and development of NPP. Therefore, this review not only contributes to deepen our understanding of the pathophysiological mechanism of NPP, but also provides theoretical basis for the development of new therapy strategies for this disorder.

The Pathological Mechanism of Neuronal Autophagy-Lysosome Dysfunction After Ischemic Stroke.

The abnormal initiation of autophagy flux in neurons after ischemic stroke caused dysfunction of autophagy-lysosome, which not only led to autophagy flux blockage, but also resulted in autophagic death of neurons. However, the pathological mechanism of neuronal autophagy-lysosome dysfunction did not form a unified viewpoint until now. In this review, taking the autophagy lysosomal dysfunction of neurons as a starting point, we summarized the molecular mechanisms that led to neuronal autophagy lysosomal dysfunction after ischemic stroke, which would provide theoretical basis for the clinical treatment of ischemic stroke.

Achieving High Expression of Cry in Green Tissues and Negligible Expression in Endosperm Simultaneously via rbcS Gene Fusion Strategy in Rice.

To allay excessive public concern about the safety of transgenic foods, and to optimize insect-resistant genes expression to delay the evolution of resistance in pests, we developed a promising strategy to fuse the GOI (gene of interest) with OsrbcS (rice small subunit of ribulose bisphosphate carboxylase/oxygenase) in transgenic rice, which acted as a carrier, driven by the OsrbcS native promoter to sequester its expression in green tissues. Using eYFP as a trial, we reported a high-level accumulation of eYFP in green tissue and almost none in the seed and root of the fused construct compared to the non-fused construct. After applying this fusion strategy in insect-resistant rice breeding, recombinant OsrbcS-Cry1Ab/Cry1Ac expressed rice plants conferred high resistance to leaffolders and striped stem borers, among which two single-copy lines possessed normal agronomic performance in the field. Specifically, Cry1Ab/Cry1Ac protein levels in single-copy construct transgenic lines ranged from 1.8 to 11.5 µg g-1 in the leaf, higher than the Actin I promoter-driven control, T51-1, about 1.78 µg g-1 in the leaf, but negligible (only 0.00012-0.00117 µg g-1) in endosperm by ELISA analysis. Our study provided a novel approach to creating Cry1Ab/Cry1Ac-free endosperm rice with a high level of insect-resistant protein in green tissues through the simultaneous usage of the OsrbcS promoter and OsrbcS as a fusion partner.

Combining Ability Analysis of Yield-Related Traits of Two Elite Rice Restorer Lines in Chinese Hybrid Rice.

Hybrid rice breeding is an important strategy for enhancing grain yield. Breeding high-performance parental lines and identifying combining abilities is a top priority for hybrid breeding. Yuenongsimiao (YNSM) and its derivative variety Yuehesimiao (YHSM) are elite restorer lines with a high ability of fertility restoration, from which 67 derived hybrid combinations have been authorized to different degrees in more than 110 instances in China. In this study, we found that YNSM and YHSM contained three candidate restorer-of-fertility (Rf) genes, Rf3, Rf4, and Rf5/Rf1a, that might confer their restoration ability. Subsequently, we investigated heterosis and combining ability of YNSM and YHSM using 50 F1 hybrids from a 5 × 10 incomplete diallelic mating design. Our results indicated that hybrid combinations exhibited significant genetic differences, and the additive effects of the parental genes played a preponderant role in the inheritance of observed traits. The metrics of plant height (PH), 1000-grain weight (TGW), panicle length (PL), and the number of spikelets per panicle (NSP) were mainly affected by genetic inheritance with higher heritability. Notably, the general combining ability (GCA) of YHSM exhibited the largest positive effect on the number of grains per panicle (NGP), NSP, PL, and TGW. Thus, YHSM had the largest GCA effect on yield per plant (YPP). In addition, the GCA of YNSM exhibited a positive impact on YPP, mainly due to the critical contribution of seed setting percentage (SSP). Moreover, YNSM and YHSM exhibited negative GCA effects on PH, implying that YNSM and YHSM could effectively enhance plant lodging resistance by reducing the plant height of the derived hybrids. Remarkably, among the hybrids, Yuanxiang A/YNSM (YXA/YNSM), Shen 08S/Yuemeizhan (S08S/YMZ), and Quan 9311A/YHSM (Q9311A/YHSM) represent promising new combinations with a higher specific combining ability (SCA) effect value on YPP with a value more than 3.50. Our research thus highlights the promising application for the rational utilization of YNSM and YHSM in hybrid rice breeding.

Complexin I knockout rats exhibit a complex neurobehavioral phenotype including profound ataxia and marked deficits in lifespan.

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1-/-). Then, we characterized the survival rate and behavioral phenotype of CPLX1-/- rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1-/- rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1-/- rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1-/- rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1-/- rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1.

Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway.

UNLABELLED: Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown. METHODS: Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively. RESULTS: AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes. CONCLUSION: This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE.

The positive role of transforming growth factor-ß1 in ischemic stroke.

Ischemic stroke is one of the most disabling and fatal diseases around the world. The damaged brain tissues will undergo excessive autophagy, vascular endothelial cells injury, blood-brain barrier (BBB) impairment and neuroinflammation after ischemic stroke. However, there is no unified viewpoint on the underlying mechanism of brain damage. Transforming growth factor-ß1 (TGF-ß1), as a multi-functional cytokine, plays a crucial role in the intricate pathological processes and helps maintain the physiological homeostasis of brain tissues through various signaling pathways after ischemic stroke. In this review, we summarize the protective role of TGF-ß1 in autophagic flux, BBB, vascular remodeling, neuroinflammation and other aspects after ischemic stroke. Based on the review, we believe that TGF-ß1 could serve as a key target for treating ischemic stroke.

Translation and validation study of the Chinese version of the service user technology acceptability questionnaire.

Objective: This study aimed to assess the reliability and validity of the translated Chinese version of the Service User Technology Acceptability Questionnaire (C-SUTAQ). Methods: Patients with cancer (n â€‹= â€‹554) from a tertiary hospital in China completed the C-SUTAQ. Item analysis, content and construct validity test, internal consistency test, and test-retest reliability analysis were conducted on the instrument to test its applicability. Results: The critical ratio of each item of the C-SUTAQ ranged from 11.869 to 29.656; the correlation of each item and subscale ranged from 0.736 to 0.929. The Cronbach's α value for each subscale ranged from 0.659 to 0.941, and the test-retest reliability ranged from 0.859 to 0.966. The content validity index of the scale level and the item level content validity index of the instrument were both 1. Exploratory factor analysis indicated it was reasonable that the C-SUTAQ consists of six subscales after rotation. Confirmatory factor analysis demonstrated good construct validity (χ2/df â€‹= â€‹2.459, comparative fit index â€‹= â€‹0.922, incremental fit index â€‹= â€‹0.907, standardized root mean square residual â€‹= â€‹0.060, root-mean-square error of approximation â€‹= â€‹0.073, goodness of fit index â€‹= â€‹0.875, normed fit index â€‹= â€‹0.876. Conclusions: The C-SUTAQ had good reliability and validity and may be useful to assess Chinese patients' acceptability of telecare. However, the small sample size limited generalization and there is a need to expand the sample to include persons with other diseases. Further studies are required using the translated questionnaire.

Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVES: Numerous studies have indicated that chronic cerebrospinal venous insufficiency is a potential factor in causing multiple sclerosis in recent years, but this conclusion remains unconfirmed. This meta-analysis examined the correlation between multiple sclerosis and chronic cerebrospinal venous insufficiency. METHODS: We searched Embase and Medline (Ovid) for publications published from 1 January 2006 to 1 May 2022. The meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eligible studies (n=20) included 3069 participants from seven countries. Pooled analysis indicated that chronic cerebrospinal venous insufficiency was more frequent in patients with multiple sclerosis than in healthy controls (OR 3.36; 95% CI 1.92 to 5.85; p<0.001) with remarkable heterogeneity among studies (I2=79%). Results were more strongly correlated in subsequent sensitivity analyses, but heterogeneity was also more substantial. We removed studies that initially proposed a chronic cerebrospinal venous insufficiency team as well as studies by authors involved in or advocating endovascular therapies. CONCLUSIONS: Chronic cerebrospinal venous insufficiency is significantly associated with multiple sclerosis and it is more prevalent in patients with multiple sclerosis than in healthy individuals, but considerable heterogeneity of results is still observed.

Grain quality characteristics analysis and application on breeding of Yuenongsimiao, a high-yielding and disease-resistant rice variety.

Rice quality is one of the main targets of rice breeding and is a complex trait that involves grain appearance, milling, cooking, eating and nutritional quality. For many years, rice breeding has contended with imbalances in rice yield, quality, and disease and lodging resistance. Here, the milling and appearance quality, cooking quality, starch rapid viscosity analyzer (RVA) profile, and nutritional quality of grains of Yuenongsimiao (YNSM), an indica rice variety with high yield, high quality and disease resistance, were determined. YNSM had excellent appearance and quality, with low amylose contents and high gel consistency, and these characteristics exhibited significant correlations with the RVA profile such as hot paste viscosity, cool paste viscosity, setback viscosity, and consistency. Moreover, 5 genes related to length-to-width ratio (LWR) as well as the Wx gene were used to detect the main quality genotype of YNSM. The results showed that YNSM is a semilong-grain rice with a relatively high brown rice rate, milled rice rate and head rice yield and low chalkiness. The results indicated that the LWR and food quality of YNSM might be related to gs3, gw7 and Wxb. This study also reports the quality characteristics of hybrid rice developed using YNSM as a restorer line. The quality characteristics and the genotype for grain quality determined through gene analysis in YNSM may facilitate the breeding of new rice varieties that achieve a balance of grain yield, resistance and quality.

The isolation of Pi1, an allele at the Pik locus which confers broad spectrum resistance to rice blast.

We report the isolation of Pi1, a gene conferring broad-spectrum resistance to rice blast (Magnaporthe oryzae). Using loss- and gain-of-function approaches, we demonstrate that Pi1 is an allele at the Pik locus. Like other alleles at this locus, Pi1 consists of two genes. A functional nucleotide polymorphism (FNP) was identified that allows differentiation of Pi1 from other Pik alleles and other non-Pik genes. A extensive germplasm survey using this FNP reveals that Pi1 is a rare allele in germplasm collections and one that has conferred durable resistance to a broad spectrum of pathogen isolates.

5-Fluorouracil reduces the fibrotic scar via inhibiting matrix metalloproteinase 9 and stabilizing microtubules after spinal cord injury.

AIMS: Fibrotic scars composed of a dense extracellular matrix are the major obstacles for axonal regeneration. Previous studies have reported that antitumor drugs promote neurofunctional recovery. METHODS: We investigated the effects of 5-fluorouracil (5-FU), a classical antitumor drug with a high therapeutic index, on fibrotic scar formation, axonal regeneration, and functional recovery after spinal cord injury (SCI). RESULTS: 5-FU administration after hemisection SCI improved hind limb sensorimotor function of the ipsilateral hind paws. 5-FU application also significantly reduced the fibrotic scar formation labeled with aggrecan and fibronectin-positive components, Iba1+ /CD11b+ macrophages/microglia, vimentin, chondroitin sulfate proteoglycan 4 (NG2/CSPG4), and platelet-derived growth factor receptor beta (PDGFRß)+ pericytes. Moreover, 5-FU treatment promoted stromal cells apoptosis and inhibited fibroblast proliferation and migration by abrogating the polarity of these cells and reducing matrix metalloproteinase 9 expression and promoted axonal growth of spinal neurons via the neuron-specific protein doublecortin-like kinase 1 (DCLK1). Therefore, 5-FU administration impedes the formation of fibrotic scars and promotes axonal regeneration to further restore sensorimotor function after SCI.

Corrigendum: Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

[This corrects the article DOI: 10.3389/fonc.2021.663262.].

The isolation and characterization of Pik, a rice blast resistance gene which emerged after rice domestication.

• The rice-rice blast pathosystem is of great interest, not only because of the damaging potential of rice blast to the rice crop, but also because both the pathogen and its host are experimentally amenable. The rice blast resistance gene Pik, which is one of the five classical alleles located at the Pik locus on the long arm of chromosome 11, confers high and stable resistance to many Chinese rice blast isolates. • The isolation and functional characterization of Pik were performed in the present study through genetic and genomic approaches. • A combination of Pik-1 and Pik-2 is required for the expression of Pik resistance. Both Pik-1 and Pik-2 encode coiled-coil nucleotide binding site leucine-rich repeat (NBS-LRR) proteins, and each shares a very high level of protein identity with corresponding proteins encoded by the Pik-m and Pik-p alleles. Pik could be distinguished from other Pik alleles, including Pik-m and Pik-p, by the allele-specific, single-nucleotide polymorphism T1-2944G. • The coupled genes probably did not evolve as a result of a duplication event, and are far from any NBS-LRR R gene characterized. Pik is a younger allele at the locus that probably emerged after rice domestication.

The role of immune cells in the course of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the central nervous system. The pathological manifestations mainly consist of α-synuclein accumulation, degeneration and death of dopaminergic neurons, and insufficient dopamine secretion. There are many pathophysiological mechanisms leading to these pathological changes. The role of autoimmunity in Parkinson's disease is one of the academic hotspots in recent years. Many types of immune cells actively participate in the pathogenesis of Parkinson's disease, such as dendritic cells, microglia, T lymphocytes, B lymphocytes and natural killer (NK) cells, which lead to abnormal immune response in Parkinson's disease patients. Therefore, this paper focuses on reviewing the research progress of immune cells in Parkinson's disease.

The genetic arms race between plant and Xanthomonas: lessons learned from TALE biology.

The pathogenic bacterial genus Xanthomonas infects a wide variety of host plants and causes devastating diseases in many crops. Transcription activator-like effectors (TALEs) are important virulence factors secreted by Xanthomonas with the ability to directly bind to the promoters of target genes in plant hosts and activate their expression, which often facilitates the proliferation of pathogens. Understanding how plants cope with TALEs will provide mechanistic insights into crop breeding for Xanthomonas defense. Over the past 30 years, numerous studies have revealed the modes of action of TALEs in plant cells and plant defense strategies to overcome TALE attack. Based on these findings, new technologies were adopted for disease management to optimize crop production. In this article, we will review the most recent advances in the evolutionary arms race between plant resistance and TALEs from Xanthomonas, with a specific focus on TALE applications in the development of novel breeding strategies for durable and broad-spectrum resistance.

Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

Glioma, the most common intracranial tumor, harbors great harm. Since the treatment for it has reached the bottleneck stage, the development of new drugs becomes a trend. Therefore, we focus on the effect of scutellarin (SCU) and its combination with C18H17NO6 (abbreviated as combination) on glioma and its possible mechanism in this study. Firstly, SCU and C18H17NO6 both suppressed the proliferation of U251 and LN229 cells in a dose-dependent manner, and C18H17NO6 augmented the inhibition effect of SCU on U251 and LN229 cells in vitro. Moreover, there was an interactive effect between them. Secondly, SCU and C18H17NO6 decreased U251 cells in G2 phase and LN229 cells in G2 and S phases but increased U251 cells in S phase, respectively. Meanwhile, the combination could further reduce U251 cells in G2 phase and LN229 cells in G2 and S phases. Thirdly, SCU and C18H17NO6 both induced the apoptosis of U251 and LN229. The combination further increased the apoptosis rate of both cells compared with the two drugs alone. Furthermore, SCU and C18H17NO6 both inhibited the lateral and vertical migration of both cells, which was further repressed by the combination. More importantly, the effect of SCU and the combination was better than positive control-temozolomide, and the toxicity was low. Additionally, SCU and C18H17NO6 could suppress the growth of glioma in vivo, and the effect of the combination was better. Finally, SCU and the combination upregulated the presenilin 1 (PSEN1) level but inactivated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling in vitro and in vivo. Accordingly, we concluded that scutellarin and its combination with C18H17NO6 suppressed the proliferation/growth and migration and induced the apoptosis of glioma, in which the mechanism might be associated with the repression of PSEN1/PI3K-AKT signaling axis.

Integrated transcriptomic and metabolomic analysis provides insight into the regulation of leaf senescence in rice.

Leaf senescence is one of the most precisely modulated developmental process and affects various agronomic traits of rice. Anti-senescence rice varieties are important for breeding application. However, little is known about the mechanisms underlying the metabolic regulatory process of leaf senescence in rice. In this study, we performed transcriptomic and metabolomic analyses of the flag leaves in Yuenong Simiao (YN) and YB, two indica rice cultivars that differ in terms of their leaf senescence. We found 8524 genes/204 metabolites were differentially expressed/accumulated in YN at 30 days after flowering (DAF) compared to 0 DAF, and 8799 genes/205 metabolites were differentially expressed in YB at 30 DAF compared to 0 DAF. Integrative analyses showed that a set of genes and metabolites involved in flavonoid pathway were significantly enriched. We identified that relative accumulation of PHENYLALANINE AMMONIA-LYASE (PAL), CINNAMATE 4-HYDROXYLASE (C4H), 4-COUMAROYL-COA LIGASE (4CL), CHALCONE SYNTHASE (CHS) and CHALCONE ISOMERASE (CHI) in YN30/0 was higher than that in YB30/0. Three flavonoid derivatives, including phloretin, luteolin and eriodictyol, showed lower abundances in YB than in YN at 30 DAF. We further revealed a MYB transcription factor, which is encoded by OsR498G0101613100 gene, could suppress the expression of CHI and CHS. Our results suggested a comprehensive analysis of leaf senescence in a view of transcriptome and metabolome and would contribute to exploring the molecular mechanism of leaf senescence in rice.

The Naturally Evolved EPSPS From Goosegrass Confers High Glyphosate Resistance to Rice.

Glyphosate-resistant crops developed by the CP4-EPSPS gene from Agrobacterium have been planted on a massive scale globally, which benefits from the high efficiency and broad spectrum of glyphosate in weed control. Some glyphosate-resistant (GR) genes from microbes have been reported, which might raise biosafety concerns. Most of them were obtained through a hygromycin-HPT transformation system. Here we reported the plant source with 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from goosegrass endowed rice with high resistance to glyphosate. The integrations and inheritability of the transgenes in the rice genome were investigated within two generations. The EiEPSPS transgenic plants displayed similar growth and development to wild type under no glyphosate selection pressure but better reproductive performance under lower glyphosate selection pressure. Furthermore, we reconstructed a binary vector pCEiEPSPS and established the whole stage glyphosate selection using the vector. The Glyphosate-pCEiEPSPS selection system showed a significantly higher transformation efficiency compared with the hygromycin-HPT transformation system. Our results provided a promising alternative gene resource to the development of GR plants and also extended the plant transformation toolbox.

Distribution of Bacterial Blight Resistance Genes in the Main Cultivars and Application of Xa23 in Rice Breeding.

Bacterial blight (BB) is an important constraint on achieving a high and stable rice grain yield. An increasing number of BB resistance (R) genes have been identified and cloned to increase the available options for rice disease resistance breeding. However, it is necessary to understand the distribution of R genes in rice varieties for rational distribution and breeding. Here, we genotyped five R genes, i.e. Xa4, Xa7, Xa21, Xa23, and Xa27, in seventy main cultivars from Guangdong Province, South China using the corresponding specific markers. Our results showed that 61 varieties carried Xa4, only three varieties carried Xa27, and Xa7, Xa21, or Xa23 was not detected in all tested varieties. Notably, only 33 varieties exhibited resistance to pathotype IV Xoo strains. These results indicate that Xa4 is no longer suitable for widespread use in rice breeding, although Xa4 is widely present in tested varieties. Remarkably, the strongly virulent BB strains of pathotype IX evolved quickly in southern China, and Xa23 was found to effectively confer resistance against the pathotype IX strains. Subsequently, we successfully bred two novel inbred rice varieties as also being restorer lines and two photoperiod- and thermo-sensitive genic male sterility (P/TGMS) lines using the broad-spectrum resistance gene Xa23 through marker-assisted selection (MAS) combined with phenotypic selection. All of the developed lines and derived hybrids exhibited enhanced resistance to BB with excellent yield performance. Our research may potentially facilitate both of the inbred and hybrid rice disease resistance breeding.