Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms.

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.

P2Y1R and P2Y2R: potential molecular triggers in muscle regeneration.

Muscle regeneration is indispensable for skeletal muscle health and daily life when injury, muscular disease, and aging occur. Among the muscle regeneration, muscle stem cells' (MuSCs) activation, proliferation, and differentiation play a key role in muscle regeneration. Purines bind to its specific receptors during muscle development, which transmit environmental stimuli and play a crucial role of modulator of muscle regeneration. Evidences proved P2R expression during development and regeneration of skeletal muscle, both in human and mouse. In contrast to P2XR, which have been extensively investigated in skeletal muscles, the knowledge of P2YR in this tissue is less comprehensive. This review summarized muscle regeneration via P2Y1R and P2Y2R and speculated that P2Y1R and P2Y2R might be potential molecular triggers for MuSCs' activation and proliferation via the p-ERK1/2 and PLC pathways, explored their cascade effects on skeletal muscle, and proposed P2Y1/2 receptors as potential pharmacological targets in muscle regeneration, to advance the purinergic signaling within muscle and provide promising strategies for alleviating muscular disease.

OsATX1 Interacts with Heavy Metal P1B-Type ATPases and Affects Copper Transport and Distribution.

Copper (Cu) is an essential micronutrient for plant growth. However, the molecular mechanisms underlying Cu trafficking and distribution to different organs in rice (Oryza sativa) are poorly understood. Here, we report the function and role of Antioxidant Protein1 (OsATX1), a Cu chaperone in rice. Knocking out OsATX1 resulted in increased Cu concentrations in roots, whereas OsATX1 overexpression reduced root Cu concentrations but increased Cu accumulation in the shoots. At the reproductive stage, the concentrations of Cu in developing tissues, including panicles, upper nodes and internodes, younger leaf blades, and leaf sheaths of the main tiller, were increased significantly in OsATX1-overexpressing plants and decreased in osatx1 mutants compared with the wild type. The osatx1 mutants also showed a higher Cu concentration in older leaves. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that OsATX1 interacts with the rice heavy metal P1B-ATPases HMA4, HMA5, HMA6, and HMA9. These results suggest that OsATX1 may function to deliver Cu to heavy metal P1B-ATPases for Cu trafficking and distribution in order to maintain Cu homeostasis in different rice tissues. In addition, heterologous expression of OsATX1 in the yeast (Saccharomyces cerevisiae) cadmium-sensitive mutant Δycf1 increased the tolerance to Cu and cadmium by decreasing their respective concentrations in the transformed yeast cells. Taken together, our results indicate that OsATX1 plays an important role in facilitating root-to-shoot Cu translocation and the redistribution of Cu from old leaves to developing tissues and seeds in rice.

Fabrication, characterization, and emulsifying properties of complex based on pea protein isolate/pectin for the encapsulation of pterostilbene.

In this study, pectin (PEC) and pea protein isolate(PPI) was successfully used to create complexes as a novel delivery system for pterostilbene (PT). When the mass ratio of PEC to PPI was 0.5, the particle size and ζ-potential of PPI-PEC-PT were 119.41 ± 5.68 nm and -23.26 ± 0.61 mV, respectively, and the encapsulation efficiency (EE) of PT was 90.92 ± 2.08%. The photochemical stability of PT was enhanced after encapsulation. The results of the molecular docking and multispectral analysis demonstrated that the PPI and PT binding was spontaneous and mostly fueled by hydrophobic interactions. The hydrophobicity of PPI was significantly decreased and the emulsification activity and emulsion stability were significantly improved after production with PEC and PT. The best emulsification impact was demonstrated by the PPI-PEC-PT complex. PPI-PEC is an effective PT delivery material, and the PPI-PEC-PT complex is a new functional emulsification material with significant potential in liquid and semi-liquid food and health products.

An Oryza-specific hydroxycinnamoyl tyramine gene cluster contributes to enhanced disease resistance.

Genomic clustering of non-homologous genes for the biosynthesis of plant defensive compounds is an emerging theme, but insights into their formation and physiological function remain limited. Here we report the identification of a newly discovered hydroxycinnamoyl tyramine (HT) gene cluster in rice. This cluster contains a pyridoxamine 5'-phosphate oxidase (OsPDX3) producing the cofactor pyridoxal 5'-phosphate (PLP), a PLP-dependent tyrosine decarboxylase (OsTyDC1), and two duplicated hydroxycinnamoyl transferases (OsTHT1 and OsTHT2). These members were combined to represent an enzymological innovation gene cluster. Natural variation analysis showed that the abundance of the toxic tyramine intermediate of the gene cluster among different rice accessions is mainly determined by the coordinated transcription of OsTyDC1 and OsTHT1. Further pathogen incubation assays demonstrated that the end products of the HT gene cluster displayed enhanced resistance to the bacterial pathogen Xanthomonas oryzae pv. Oryzae (Xoo) and fungal pathogen Magnaporthe oryzae (M. oryzae), and the enhanced resistance is associated with the boost of phytoalexins and the activation of defense response. The unique presence of the HT gene cluster in Oryza AA genome, together with the enrichment of transposon elements within this gene cluster region, provides an evolutionary background to accelerate cluster member combinations. Our study not only discovered a gene cluster involved in the phenylpropanoid metabolism but also addressed the key aspects of gene cluster formation. In addition, our results provide a new metabolic pool for plant defense against pathogens.

A monocot-specific hydroxycinnamoylputrescine gene cluster contributes to immunity and cell death in rice.

Phenolamides (PAs), a diverse group of specialized metabolites, including hydroxycinnamoylputrescine (HP), hydroxycinnamoylagmatine, and hydroxycinnamoyltryptamine, are important in plant resistance to biotic stress. However, the genes involved in the biosynthesis and modulation of PAs have not been fully elucidated. This study identified an HP biosynthetic gene cluster in rice (Oryza sativa) comprising one gene (OsODC) encoding a decarboxylase and two tandem-duplicated genes (OsPHT3 and OsPHT4) encoding putrescine hydroxycinnamoyl acyltransferases coexpressed in different tissues. OsODC catalyzes the conversion of ornithine to putrescine, which is used in HP biosynthesis involving OsPHT3 and OsPHT4. OsPHT3 or OsPHT4 overexpression causes HP accumulation and cell death and putrescine hydroxycinnamoyl acyltransferases (PHT) activity-dependent resistance against the fungal pathogen Magnaporthe oryzae. OsODC overexpression plants also confer enhanced resistance to M. oryzae. Notably, the basic leucine zipper transcription factor APIP5, a negative regulator of cell death, directly binds to the OsPHT4 promoter, repressing its transcription. Moreover, APIP5 suppression induces OsPHT4 expression and HP accumulation. Comparative genomic analysis revealed that the HP biosynthetic gene cluster is conserved in monocots. These results characterized a previously unidentified monocot-specific gene cluster that is involved in HP biosynthesis and contributes to defense and cell death in rice.

Genome-wide Dissection of Co-selected UV-B Responsive Pathways in the UV-B Adaptation of Qingke.

Qingke (Tibetan hulless barley) has long been cultivated and exposed to long-term and strong UV-B radiation on the Tibetan Plateau, which renders it an ideal species for elucidating novel UV-B responsive mechanisms in plants. Here we report a comprehensive metabolite profiling and metabolite-based genome-wide association study (mGWAS) using 196 diverse qingke and barley accessions. Our results demonstrated both constitutive and induced accumulation, and common genetic regulation, of metabolites from different branches of the phenylpropanoid pathway that are involved in UV-B protection. A total of 90 significant mGWAS loci for these metabolites were identified in barley-qingke differentiation regions, and a number of high-level metabolite trait alleles were found to be significantly enriched in qingke, suggesting co-selection of various phenylpropanoids. Upon dissecting the entire phenylpropanoid pathway, we identified some key determinants controlling natural variation of phenylpropanoid content, including three novel proteins, a flavone C-pentosyltransferase, a tyramine hydroxycinnamoyl acyltransferase, and a MYB transcription factor. Our study, furthermore, demonstrated co-selection of both constitutive and induced phenylpropanoids for UV-B protection in qingke.

Selection of a subspecies-specific diterpene gene cluster implicated in rice disease resistance.

Diterpenoids are the major group of antimicrobial phytoalexins in rice1,2. Here, we report the discovery of a rice diterpenoid gene cluster on chromosome 7 (DGC7) encoding the entire biosynthetic pathway to 5,10-diketo-casbene, a member of the monocyclic casbene-derived diterpenoids. We revealed that DGC7 is regulated directly by JMJ705 through methyl jasmonate-mediated epigenetic control3. Functional characterization of pathway genes revealed OsCYP71Z21 to encode a casbene C10 oxidase, sought after for the biosynthesis of an array of medicinally important diterpenoids. We further show that DGC7 arose relatively recently in the Oryza genus, and that it was partly formed in Oryza rufipogon and positively selected for in japonica during domestication. Casbene-synthesizing enzymes that are functionally equivalent to OsTPS28 are present in several species of Euphorbiaceae but gene tree analysis shows that these and other casbene-modifying enzymes have evolved independently. As such, combining casbene-modifying enzymes from these different families of plants may prove effective in producing a diverse array of bioactive diterpenoid natural products.

Role of surface functionalities of nanoplastics on their transport in seawater-saturated sea sand.

The transport and retention of nanoplastics (NP, 200 nm nanopolystyrene) functionalized with surface carboxyl (NPC), sulfonic (NPS), low-density amino (negatively charged, NPA-), and high-density amino (positively charged, NPA+) groups in seawater-saturated sand with/without humic acid were examined to explore the role of NP surface functionalities. The mass percentages of NP recovered from the effluent (Meff) with a salinity of 35 practical salinity units (PSU) were ranked as follows: NPC (19.69%) > NPS (16.37%) > NPA+ (13.33%) > NPA- (9.78%). The homoaggregation of NPS and NPA- was observed in seawater. The transport of NPA- exhibited a ripening phenomenon (i.e., a decrease in the transport rate with time) due to the high attraction of NP with previously deposited NP, whereas monodispersed NPA+ presented a low Meff value because of the electrostatic attraction between NPA+ and negatively charged sand. Retention experiments showed that the majority of NPC, NPS and NPA+ accumulated in a monolayer on the sand surface, whereas NPA- accumulated in multiple layers. Suwannee River humic acid (SRHA) could remarkably improve the transportability of NPC, NPS, and NPA- by increasing steric repulsion. The strong attraction between NPA+ and the deposited NPA+ in the presence of SRHA triggered the weak ripening phenomenon. As seawater salinity decreased from 35 PSU to 3.5 PSU, the increase in electrostatic repulsion of NP-NP and NP-sand enhanced the transport of NPC, NPS, and NPA-, and the ripening of NPA- breakthrough curves disappeared. In deionized water, NPC, NPS, and NPA- achieved complete column breakthrough because the electrostatic repulsion between NP and sand intensified. However, the Meff values of NPA+ in 3.5 PSU seawater and deionized water presented limited increments of 15.49% and 23.67%, respectively. These results indicated that the fate of NP in sandy marine environments were strongly affected by NP surface functionalities, seawater salinity, and coexisting SRHA.

Influences of Alkyl and Aryl Substituents on Iminopyridine Fe(II)- and Co(II)-Catalyzed Isoprene Polymerization.

A series of alkyl- and aryl-substituted iminopyridine Fe(II) complexes 1a⁻7a and Co(II) complexes 2b, 3b, 5b, and 6b were synthesized. The activator effect, influence of temperature, and, particularly, the alkyl and aryl substituents' effect on catalytic activity, polymer molecular weight, and regio-/stereoselectivity were investigated when these complexes were applied in isoprene polymerization. All of the Fe(II) complexes afforded polyisoprene with high molecular weight and moderate cis-1,4 selectivity. In contrast, the Co(II) complexes produced polymers with low molecular weight and relatively high cis-1,4 selectivity. In the iminopyridine Fe(II) system, the alkyl and aryl substituents' effect exhibits significant variation on the isoprene polymerization. In the iminopyridine Co(II) system, there is little influence observed on isoprene polymerization by alkyl and aryl substituents.