Deficiency in flavonoid biosynthesis genes CHS, CHI, and CHIL alters rice flavonoid and lignin profiles.

Lignin is a complex phenylpropanoid polymer deposited in the secondary cell walls of vascular plants. Unlike most gymnosperm and eudicot lignins that are generated via the polymerization of monolignols, grass lignins additionally incorporate the flavonoid tricin as a natural lignin monomer. The biosynthesis and functions of tricin-integrated lignin (tricin-lignin) in grass cell walls and its effects on the utility of grass biomass remain largely unknown. We herein report a comparative analysis of rice (Oryza sativa) mutants deficient in the early flavonoid biosynthetic genes encoding CHALCONE SYNTHASE (CHS), CHALCONE ISOMERASE (CHI), and CHI-LIKE (CHIL), with an emphasis on the analyses of disrupted tricin-lignin formation and the concurrent changes in lignin profiles and cell wall digestibility. All examined CHS-, CHI-, and CHIL-deficient rice mutants were largely depleted of extractable flavones, including tricin, and nearly devoid of tricin-lignin in the cell walls, supporting the crucial roles of CHS and CHI as committed enzymes and CHIL as a noncatalytic enhancer in the conserved biosynthetic pathway leading to flavone and tricin-lignin formation. In-depth cell wall structural analyses further indicated that lignin content and composition, including the monolignol-derived units, were differentially altered in the mutants. However, regardless of the extent of the lignin alterations, cell wall saccharification efficiencies of all tested rice mutants were similar to that of the wild-type controls. Together with earlier studies on other tricin-depleted grass mutant and transgenic plants, our results reflect the complexity in the metabolic consequences of tricin pathway perturbations and the relationships between lignin profiles and cell wall properties.

Alternative Splicing and Its Roles in Plant Metabolism.

Plant metabolism, including primary metabolism such as tricarboxylic acid cycle, glycolysis, shikimate and amino acid pathways as well as specialized metabolism such as biosynthesis of phenolics, alkaloids and saponins, contributes to plant survival, growth, development and interactions with the environment. To this end, these metabolic processes are tightly and finely regulated transcriptionally, post-transcriptionally, translationally and post-translationally in response to different growth and developmental stages as well as the constantly changing environment. In this review, we summarize and describe the current knowledge of the regulation of plant metabolism by alternative splicing, a post-transcriptional regulatory mechanism that generates multiple protein isoforms from a single gene by using alternative splice sites during splicing. Numerous genes in plant metabolism have been shown to be alternatively spliced under different developmental stages and stress conditions. In particular, alternative splicing serves as a regulatory mechanism to fine-tune plant metabolism by altering biochemical activities, interaction and subcellular localization of proteins encoded by splice isoforms of various genes.

Phylogeny and conservation of plant U2A/U2A', a core splicing component in U2 spliceosomal complex.

MAIN CONCLUSION: This study systematically identifies 112 U2A genes from 80 plant species by combinatory bioinformatics analysis, which is important for understanding their phylogenetic history, expression profiles and for predicting specific functions. In eukaryotes, a pre-mRNA can generate multiple transcripts by removing certain introns and joining corresponding exons, thus greatly expanding the transcriptome and proteome diversity. The spliceosome is a mega-Dalton ribonucleoprotein (RNP) complex that is essential for the process of splicing. In spliceosome components, the U2 small nuclear ribonucleoprotein (U2 snRNP) forms the pre-spliceosome by association with the branch site. An essential component that promotes U2 snRNP assembly, named U2A, has been extensively identified in humans, yeast and nematodes. However, studies examining U2A genes in plants are scarce. In this study, we performed a comprehensive analysis and identified a total of 112 U2A genes from 80 plant species representing dicots, monocots, mosses and algae. Comparisons of the gene structures, protein domains, and expression patterns of 112 U2A genes indicated that the conserved functions were likely retained by plant U2A genes and important for responses to internal and external stimuli. In addition, analysis of alternative transcripts and splice sites of U2A genes indicated that the fifth intron contained a conserved alternative splicing event that might be important for its molecular function. Our work provides a general understanding of this splicing factor family in terms of genes and proteins, and it will serve as a fundamental resource that will contribute to further mechanistic characterization in plants.

Microplastics in a Remote Lake Basin of the Tibetan Plateau: Impacts of Atmospheric Transport and Glacial Melting.

Plastic pollution is fast becoming one of the most pressing global issues that we currently face. Remote areas, such as the polar regions and the Tibetan Plateau, are now also exposed to microplastic contamination. However, with the impact of global warming, the transport of microplastics within the glacier-lake basins in such regions remains unclear. In this work, the Nam Co Basin in the Tibetan Plateau was selected to study the characteristics of microplastics in the rain fallout, lake water, glacial runoff, and non-glacial runoff. Fiber and films were the most common microplastic morphologies in all water samples; a higher proportion (37%) of light-weighing polypropylene and small-size (50-300 µm, ∼30%) microplastics were found in the glacial runoff. Air mass trajectory analysis showed that microplastics could be transported through the atmosphere over a distance of up to 800 km. For microplastic loading in lakes, the atmospheric fallout was estimated to be 3.3 tons during the monsoon season, whereas the contributions of glacial runoff (∼41 kg) and non-glacial runoff (∼522 kg) were relatively low. For the microplastic loading in glaciers, the atmospheric deposition was ∼500 kg/yr, and the output caused by glacial melting only accounted 8% of the total atmospheric input. All these results suggested that the dominant pathway through which microplastics enter remote mountainous lake basins is atmospheric deposition, and once deposited on glaciers, microplastics will be stored for a long time. This work provides quantitative evidence elucidating the fate of microplastics in alpine lake environments.

Convergent recruitment of 5'-hydroxylase activities by CYP75B flavonoid B-ring hydroxylases for tricin biosynthesis in Medicago legumes.

Tricin (3',5'-dimethoxylated flavone) is a predominant flavonoid amongst monocots but occurs only in isolated and unrelated dicot lineages. Although tricin biosynthesis has been intensively studied in monocots, it has remained largely elusive in tricin-accumulating dicots. We investigated a subgroup of cytochrome P450 (CYP) 75B subfamily flavonoid B-ring hydroxylases (FBHs) from two tricin-accumulating legumes, Medicago truncatula and alfalfa (Medicago sativa), by phylogenetic, molecular, biochemical and mutant analyses. Five Medicago cytochrome P450 CYP75B FBHs are phylogenetically distant from other legume CYP75B members. Among them, MtFBH-4, MsFBH-4 and MsFBH-10 were expressed in tricin-accumulating vegetative tissues. In vitro and in planta analyses demonstrated that these proteins catalyze 3'- and 5'-hydroxylations critical to tricin biosynthesis. A key amino acid polymorphism, T492G, at their substrate recognition site 6 domain is required for the novel 5'-hydroxylation activities. Medicago truncatula mtfbh-4 mutants were tricin-deficient, indicating that MtFBH-4 is indispensable for tricin biosynthesis. Our results revealed that these Medicago legumes had acquired the tricin pathway through molecular evolution of CYP75B FBHs subsequent to speciation from other nontricin-accumulating legumes. Moreover, their evolution is independent of that of grass-specific CYP75B apigenin 3'-hydroxylases/chrysoeriol 5'-hydroxylases dedicated to tricin production and Asteraceae CYP75B flavonoid 3',5'-hydroxylases catalyzing the production of delphinidin-based pigments.

The Wheat Lr67 Gene from the Sugar Transport Protein 13 Family Confers Multipathogen Resistance in Barley.

Fungal pathogens are a major constraint to global crop production; hence, plant genes encoding pathogen resistance are important tools for combating disease. A few resistance genes identified to date provide partial, durable resistance to multiple pathogens and the wheat (Triticum aestivum) Lr67 hexose transporter variant (Lr67res) fits into this category. Two amino acids differ between the wild-type and resistant alleles - G144R and V387L. Exome sequence data from 267 barley (Hordeum vulgare) landraces and wild accessions was screened and neither of the Lr67res mutations was detected. The barley ortholog of Lr67, HvSTP13, was functionally characterized in yeast as a high affinity hexose transporter. The G144R mutation was introduced into HvSTP13 and abolished Glc uptake, whereas the V387L mutation reduced Glc uptake by ∼ 50%. Glc transport by HvSTP13 heterologously expressed in yeast was reduced when coexpressed with Lr67res Stable transgenic Lr67res barley lines exhibited seedling resistance to the barley-specific pathogens Puccinia hordei and Blumeria graminis f. sp. hordei, which cause leaf rust and powdery mildew, respectively. Barley plants expressing Lr67res exhibited early senescence and higher pathogenesis-related (PR) gene expression. Unlike previous observations implicating flavonoids in the resistance of transgenic sorghum (Sorghum bicolor) expressing Lr34res, another wheat multipathogen resistance gene, barley flavonoids are unlikely to have a role in Lr67res-mediated resistance. Similar to observations made in yeast, Lr67res reduced Glc uptake in planta These results confirm that the pathway by which Lr67res confers resistance to fungal pathogens is conserved between wheat and barley.

Flavonoids are indispensable for complete male fertility in rice.

Flavonoids are essential for male fertility in some but not all plant species. In rice (Oryza sativa), the chalcone synthase mutant oschs1 produces flavonoid-depleted pollen and is male sterile. The mutant pollen grains are viable with normal structure, but they display reduced germination rate and pollen-tube length. Analysis of oschs1/+ heterozygous lines shows that pollen flavonoid deposition is a paternal effect and fertility is independent of the haploid genotypes (OsCHS1 or oschs1). To understand which classes of flavonoids are involved in male fertility, we conducted detailed analysis of rice mutants for branch-point enzymes of the downstream flavonoid pathways, including flavanone 3-hydroxylase (OsF3H; flavonol pathway entry enzyme), flavone synthase II (CYP93G1; flavone pathway entry enzyme), and flavanone 2-hydroxylase (CYP93G2; flavone C-glycoside pathway entry enzyme). Rice osf3h and cyp93g1 cyp93g2 CRISPR/Cas9 mutants, and cyp93g1 and cyp93g2 T-DNA insertion mutants showed altered flavonoid profiles in anthers, but only the osf3h and cyp93g1 cyp93g2 mutants displayed reduction in seed yield. Our findings indicate that flavonoids are essential for complete male fertility in rice and a combination of different classes (flavanones, flavonols, flavones, and flavone C-glycosides) appears to be important, as opposed to the essential role played primarily by flavonols that has been previously reported in several plant species.

Alternative splicing is a Sorghum bicolor defense response to fungal infection.

MAIN CONCLUSION: This study provides new insights that alternative splicing participates with transcriptional control in defense responses to Colletotrichum sublineola in sorghum In eukaryotic organisms, alternative splicing (AS) is an important post-transcriptional mechanism to generate multiple transcript isoforms from a single gene. Protein variants translated from splicing isoforms may have altered molecular characteristics in signal transduction and metabolic activities. However, which transcript isoforms will be translated into proteins and the biological functions of the resulting proteoforms are yet to be identified. Sorghum is one of the five major cereal crops, but its production is severely affected by fungal diseases. For example, sorghum anthracnose caused by Colletotrichum sublineola greatly reduces grain yield and biomass production. In this study, next-generation sequencing technology was used to analyze C. sublineola-inoculated sorghum seedlings compared with mock-inoculated control. It was identified that AS regulation may be as important as traditional transcriptional control during defense responses to fungal infection. Moreover, several genes involved in flavonoid and phenylpropanoid biosynthetic pathways were found to undergo multiple AS modifications. Further analysis demonstrated that non-conventional targets of both 5'- and 3'-splice sites were alternatively used in response to C. sublineola infection. Splicing factors were also affected at both transcriptional and post-transcriptional levels. As the first transcriptome report on C. sublineola infected sorghum, our work also suggested that AS plays crucial functions in defense responses to fungal invasion.

Recruitment of specific flavonoid B-ring hydroxylases for two independent biosynthesis pathways of flavone-derived metabolites in grasses.

In rice (Oryza sativa), OsF2H and OsFNSII direct flavanones to independent pathways that form soluble flavone C-glycosides and tricin-type metabolites (both soluble and lignin-bound), respectively. Production of soluble tricin metabolites requires CYP75B4 as a chrysoeriol 5'-hydroxylase. Meanwhile, the close homologue CYP75B3 is a canonical flavonoid 3'-hydroxylase (F3'H). However, their precise roles in the biosynthesis of soluble flavone C-glycosides and tricin-lignins in cell walls remain unknown. We examined CYP75B3 and CYP75B4 expression in vegetative tissues, analyzed extractable flavonoid profiles, cell wall structure and digestibility of their mutants, and investigated catalytic activities of CYP75B4 orthologues in grasses. CYP75B3 and CYP75B4 showed co-expression patterns with OsF2H and OsFNSII, respectively. CYP75B3 is the sole F3'H in flavone C-glycosides biosynthesis, whereas CYP75B4 alone provides sufficient 3',5'-hydroxylation for tricin-lignin deposition. CYP75B4 mutation results in production of apigenin-incorporated lignin and enhancement of cell wall digestibility. Moreover, tricin pathway-specific 3',5'-hydroxylation activities are conserved in sorghum CYP75B97 and switchgrass CYP75B11. CYP75B3 and CYP75B4 represent two different pathway-specific enzymes recruited together with OsF2H and OsFNSII, respectively. Interestingly, the OsF2H-CYP75B3 and OsFNSII-CYP75B4 pairs appear to be conserved in grasses. Finally, manipulation of tricin biosynthesis through CYP75B4 orthologues can be a promising strategy to improve digestibility of grass biomass for biofuel and biomaterial production.

Nonlinear relationship between platelet count and 30-day in-hospital mortality in intensive care unit stroke patients: a multicenter retrospective cohort study.

Background: Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients. Methods: We conducted a multicenter retrospective cohort study using data from 8,029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality. Results: The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223 × 109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163 × 109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant. Conclusion: This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163 × 109/L can reduce 30-day in-hospital mortality in these patients.

Hydrogen sulfide regulates ethylene-induced stomatal closure in Arabidopsis thaliana.

Hydrogen sulfide (H2 S) is a newly-discovered signaling molecule in plants and has caused increasing attention in recent years, but its function in stomatal movement is unclear. In plants, H2 S is synthesized via cysteine degradation catalyzed by D-/L-cysteine desulfhydrase (D-/L-CDes). AtD-/L-CDes::GUS transgenic Arabidopsis thaliana (L.) Heynh. plants were generated and used to investigate gene expression patterns, and results showed that AtD-/L-CDes can be expressed in guard cells. We also determined the subcellular localization of AtD-/L-CDes using transgenic plants of AtD-/L-CDes::GFP, and the results showed that AtD-CDes and AtL-CDes are located in the chloroplast and in the cytoplasm, respectively. The transcript levels of AtD-CDes and AtL-CDes were affected by the chemicals that cause stomatal closure. Among these factors, ACC, a precursor of ethylene, has the most significant effect, which indicates that the H2 S generated from D-/L-CDes may play an important role in ethylene-induced stomatal closure. Meanwhile, H2 S synthetic inhibitors significantly inhibited ethylene-induced stomatal closure in Arabidopsis. Ethylene treatment caused an increase of H2 S production and of AtD-/L-CDes activity in Arabidopsis leaves. AtD-/L-CDes over-expressing plants exhibited enhanced induction of stomatal closure compared to the wild-type after ethylene treatment; however, the effect was not observed in the Atd-cdes and Atl-cdes mutants. In conclusion, our results suggest that the D-/L-CDes-generated H2 S is involved in the regulation of ethylene-induced stomatal closure in Arabidopsis thaliana.

Spatial profiling of microbial communities by sequential FISH with error-robust encoding.

Spatial analysis of microbiomes at single cell resolution with high multiplexity and accuracy has remained challenging. Here we present spatial profiling of a microbiome using sequential error-robust fluorescence in situ hybridization (SEER-FISH), a highly multiplexed and accurate imaging method that allows mapping of microbial communities at micron-scale. We show that multiplexity of RNA profiling in microbiomes can be increased significantly by sequential rounds of probe hybridization and dissociation. Combined with error-correction strategies, we demonstrate that SEER-FISH enables accurate taxonomic identification in complex microbial communities. Using microbial communities composed of diverse bacterial taxa isolated from plant rhizospheres, we apply SEER-FISH to quantify the abundance of each taxon and map microbial biogeography on roots. At micron-scale, we identify clustering of microbial cells from multiple species on the rhizoplane. Under treatment of plant metabolites, we find spatial re-organization of microbial colonization along the root and alterations in spatial association among microbial taxa. Taken together, SEER-FISH provides a useful method for profiling the spatial ecology of complex microbial communities in situ.

Decreased serum BDNF contributes to the onset of REM sleep behavior disorder in Parkinson's disease patients.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. BDNF enhances the survival of dopaminergic neurons and improves dopaminergic neurotransmission and motor performance in patients with Parkinson's disease (PD). However, the association between BDNF levels and rapid eye movement (REM) sleep behavior disorder (RBD) in PD patients has received limited attention. METHODS: We employed the Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong version (RBDQ-HK) and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) for RBD diagnosis. Patients were categorized into three groups: healthy controls (n = 53), PD patients without RBD (PD-nRBD; n = 56), and PD patients with RBD (PD-RBD; n = 45). Serum BDNF concentrations, demographic information, medical history, and motor/non-motor manifestations were compared between the three groups. Logistic regression analysis was performed to identify independent factors associated with PD and RBD. P-trend analysis was used to assess the relationship between BDNF levels and the risk of PD and RBD onset. Interaction effects were analyzed between BDNF, patients' age, and gender on the risk of RBD onset in PD patients. RESULTS: Our findings indicate that serum BDNF levels were significantly lower in PD patients compared to healthy controls (p < 0.001). PD-RBD patients exhibited higher motor symptom scores (UPDRS III) than PD-nRBD patients (p = 0.021). Additionally, the PD-RBD group demonstrated lower cognitive function scores as measured by the Montreal Cognitive Assessment (MoCA) (p < 0.001) and Mini-Mental State Examination (MMSE) (p = 0.015). PD-RBD patients displayed significantly lower BDNF levels compared to both PD-nRBD and healthy control groups (p < 0.001). Univariate and multivariate logistic regression analyses showed that reduced BDNF levels were associated with an increased risk of RBD in PD patients (p = 0.005). P-trend analysis further confirmed the progressive relationship between decreased BDNF levels and the risk of PD and RBD onset. Furthermore, our interaction analysis highlighted the importance of monitoring younger PD patients with low serum BDNF levels for potential RBD onset. CONCLUSIONS: This study illustrates that decreased serum BDNF levels may be linked to the development of RBD in PD patients, highlighting the potential utility of BDNF as a biomarker in clinical practice.

Regioselective stilbene O-methylations in Saccharinae grasses.

O-Methylated stilbenes are prominent nutraceuticals but rarely produced by crops. Here, the inherent ability of two Saccharinae grasses to produce regioselectively O-methylated stilbenes is reported. A stilbene O-methyltransferase, SbSOMT, is first shown to be indispensable for pathogen-inducible pterostilbene (3,5-bis-O-methylated) biosynthesis in sorghum (Sorghum bicolor). Phylogenetic analysis indicates the recruitment of genus-specific SOMTs from canonical caffeic acid O-methyltransferases (COMTs) after the divergence of Sorghum spp. from Saccharum spp. In recombinant enzyme assays, SbSOMT and COMTs regioselectively catalyze O-methylation of stilbene A-ring and B-ring respectively. Subsequently, SOMT-stilbene crystal structures are presented. Whilst SbSOMT shows global structural resemblance to SbCOMT, molecular characterizations illustrate two hydrophobic residues (Ile144/Phe337) crucial for substrate binding orientation leading to 3,5-bis-O-methylations in the A-ring. In contrast, the equivalent residues (Asn128/Asn323) in SbCOMT facilitate an opposite orientation that favors 3'-O-methylation in the B-ring. Consistently, a highly-conserved COMT is likely involved in isorhapontigenin (3'-O-methylated) formation in wounded wild sugarcane (Saccharum spontaneum). Altogether, our work reveals the potential of Saccharinae grasses as a source of O-methylated stilbenes, and rationalize the regioselectivity of SOMT activities for bioengineering of O-methylated stilbenes.

Direct Detection of Antibiotic Resistance in Chinese Helicobacter pylori Clinical Isolates by Sequencing-Based Approach.

Objective: The detection of Helicobacter pylori mutations that result in antimicrobial resistance can serve as a guideline of antimicrobial therapeutics and probably prevent the failure of clinical treatments. Evaluating the potential of Sanger sequencing to identify genetically resistant determinants in Helicobacter pylori clinical isolates will be important. Methods: 180 cultured strains have been tested using agar dilution for antibiotic susceptibility. NCBI BLAST was used to perform genotypic analysis on the sequencing data. Sanger sequencing was evaluated as an alternative method to detect resistant genotypes and susceptibility. Results: By the conventional E-test, resistance to levofloxacin, amoxicillin, metronidazole, and clarithromycin was 67.3%, 15.1%, 96.4%, and 25.5%, respectively. In contrast, tetracycline had no resistance. Resistance to multiple drugs was observed in 8.12% of the strains. The genetic determinants of resistance to CLA was 23s rRNA, the determinants of resistance to amoxicillin was Pbp1, the determinants of resistance to metronidazole was rdxA, and the determinants of resistance to levofloxacin were GyrA and GyrB. However, there was no association of resistance in tetracycline. Conclusion: We found increased rates of metronidazole antibiotic resistance, highlighting the necessity for alternative therapies and periodic evaluation. Sanger sequencing has proved to be highly effective and holds the potential to be implemented in policies catering to local treatments.

Peripheral blood inflammatory cytokines are associated with rapid eye movement sleep behavior disorder in Parkinson's disease.

OBJECTIVE: Previous studies have shown the essential role of inflammation in rapid eye movement (REM) sleep behavior disorder (RBD). However, the association of RBD in Parkinson's disease (PD) with peripheral blood inflammatory cytokines is still unknown. We investigated the relationship between inflammatory cytokines and the clinical characteristics of PD patients with RBD. METHODS: A total of 153 PD patients and 36 healthy controls were included in this study, and blood plasma was collected. PD patients were classified as PD with RBD (PD-RBD, n = 60) and PD without RBD (PD-nRBD, n = 93). Inflammatory factor levels were compared among the control, PD-RBD, and PD-nRBD groups. RESULTS: The PD-RBD group had significantly higher C-reactive protein (CRP) levels (P < 0.001), monocytes (P = 0.003), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), whereas this group has lower lymphocytes levels (P < 0.001) and lymphocyte-to-monocyte ratio (LMR) (P < 0.001) than the PD-nRBD group. Univariate and multivariate logistic regression analysis indicated that LMR (P < 0.0001 odds ratio [OR] = 0.424) was a protective factor, whereas CRP (P < 0.001 OR = 2.326) was a risk factor for the PD-RBD group. PD-RBD patients had lower Montreal Cognitive Assessment (Beijing version) (MoCA) (P < 0.001) and Mini-Mental State Examination (MMSE) (P = 0.039) scores than PD-nRBD patients. CONCLUSIONS: Significant differences were found in inflammation levels between PD-RBD and PD-nRBD, suggesting that inflammatory factors are associated with the pathogenesis of RBD in PD patients. Thus, CRP and LMR levels may serve as biomarkers and predict the prognosis of PD patients with RBD.

Multifaceted roles of flavonoids mediating plant-microbe interactions.

Plant-microbe interactions dynamically affect plant growth, health, and development. The mechanisms underpinning these associations are-to a large extent-mediated by specialized host-derived secondary metabolites. Flavonoids are one of the most studied classes of such metabolites, regulating both plant development and the interaction with commensal microbes. Here, we provide a comprehensive review of the multiple roles of flavonoids in mediating plant-microbe interactions. First, we briefly summarize the general aspects of flavonoid synthesis, transport, and exudation in plants. Then, we review the importance of flavonoids regulating plant-microbe interactions and dynamically influencing the overall community assembly of plant-root microbiomes. Last, we highlight potential knowledge gaps in our understanding of how flavonoids determine the interactions between plants and commensal microbes. Collectively, we advocate the importance of advancing research in this area toward innovative strategies to effectively manipulate plant-microbiome composition, in this case, via flavonoid production and exudation in plant roots. Video Abstract.

Effects of repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex on excessive daytime sleepiness in patients with Parkinson's disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common sleep disorder in Parkinson's disease (PD), which seriously affects patients' quality of life. Repetitive transcranial magnetic stimulation (rTMS) can be used as an add-on therapy to a variety of non-motor symptoms of PD. However, little is known on the treatment of EDS in PD patients. OBJECTIVE: To explore the effects of low frequency rTMS over right dorsolateral prefrontal cortex (DLPFC) in the treatment of EDS in PD. METHODS: We conducted a sham-controlled, parallel study including 25 individuals of PD with possible EDS based on Epworth Sleepiness Scale (ESS ≥8 points) and randomly divided them into active group (n = 15) and sham group (n = 10). 1 Hz rTMS was administrated over right DLPFC for 10 consecutive days. In the active group, we further classified them into responsive group and non-responsive group according to change of ESS score in comparison with baseline. Clinical assessments on motor and non-motor symptoms were completed at baseline, at the end of treatment and 1 month after treatment. RESULTS: Compared to baseline, active group showed significant improvement on ESS score 10 days and 1 month after treatment (P < 0.05 for both). The percentage change of ESS score was positively related to disease duration during follow-up. No significant changes were observed on ESS score change in the sham group. Further analysis of individuals in the active group showed that, relative to those with non-response to rTMS, individuals with therapeutic response exhibited longer disease duration and lower baseline levodopa equivalent dose. CONCLUSION: Low frequency rTMS over right DLPFC may improve symptoms of EDS in PD.

Acute Sleep Deprivation Impairs Motor Inhibition in Table Tennis Athletes: An ERP Study.

Excellent response inhibition is the basis for outstanding competitive athletic performance, and sleep may be an important factor affecting athletes' response inhibition. This study investigates the effect of sleep deprivation on athletes' response inhibition, and its differentiating effect on non-athlete controls' performance, with the aim of helping athletes effectively improve their response inhibition ability through sleep pattern manipulation. Behavioral and event-related potential (ERP) data were collected from 36 participants (16 table tennis athletes and 20 general college students) after 36 h of sleep deprivation using ERP techniques and a stop-signal task. Sleep deprivation's different effects on response inhibition in the two groups were explored through repeated-measures ANOVA. Behavioral data showed that in a baseline state, stop-signal response time was significantly faster in table tennis athletes than in non-athlete controls, and appeared significantly longer after sleep deprivation in both groups. ERP results showed that at baseline state, N2, ERN, and P3 amplitudes were lower in table tennis athletes than in non-athlete controls, and corresponding significant decreases were observed in non-athlete controls after 36 h of sleep deprivation. Table tennis athletes showed a decrease in P3 amplitude and no significant difference in N2 and ERN amplitudes, after 36 h of sleep deprivation compared to the baseline state. Compared to non-athlete controls, table tennis athletes had better response inhibition, and the adverse effects of sleep deprivation on response inhibition occurred mainly in the later top-down motor inhibition process rather than in earlier automated conflict detection and monitoring.