Table_1_Circulating metabolites and depression: a bidirectional Mendelian randomization.XLSX

BackgroundStudies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.MethodsIn this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and “leave-one-out” methods.ResultsApolipoprotein A-I (OR 0.990, 95% CI 981–0.999) and glutamine (OR 0.985, 95% CI 0.972–0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009–1.034), glycoproteins (OR 1.005, 95% CI 1.000–1.009), isoleucine (OR 1.013, 95% CI 1.002–1.024), and urea (OR 1.020, 95% CI 1.000–1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.ConclusionIn this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.</p

Data_Sheet_1_Impairments to the multisensory integration brain regions during migraine chronification: correlation with the vestibular dysfunction.docx

ObjectivesMigraine is often combined with vestibular dysfunction, particularly in patients with chronic migraine (CM). However, the pathogenesis of migraine chronification leading to vestibular dysfunction is not fully understood. The current study investigated whether structural or functional impairments to the brain during migraine chronification could be associated with vestibular dysfunction development.MethodsThe eligible participants underwent clinical assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) determined structural impairment by evaluating alterations in gray matter volume (GMV). Functional impairment was assessed by the mean amplitude of low-frequency fluctuation (mALFF). Furthermore, the resting-state functional connectivity (rsFC) of regions possessing impairment was examined with a seed-based approach. We also analyzed the correlations between altered neuroimaging features with clinical variables and performed multiple linear regression.ResultsEighteen CM patients, 18 episodic migraine (EM) patients, and 18 healthy controls (HCs) were included in this study. A one-way ANOVA indicated the group differences in mALFF. These were located within right supramarginal gyrus (SMG), left angular gyrus (AG), middle frontal gyrus (MFG), left middle occipital gyrus (MOG), right rolandic operculum (Rol) and left superior parietal gyrus (SPG). During rsFC analysis, the CM group had more enhanced rsFC of left SPG with left MOG than the EM and HC groups. The EM group revealed enhanced rsFC of left SPG with left AG than the CM and HC groups. In multiple linear regression, after controlling for age, body mass index (BMI) and disease duration, the rsFC of left SPG with left MOG (β = 48.896, p = 0.021) was found to predict the total Dizziness Handicap Inventory (DHI) score with an explained variance of 25.1%. Moreover, the rsFC of left SPG with left MOG (β = 1.253, p = 0.003) and right SMG (β = −1.571, p = 0.049) were significant predictors of migraine frequency, accounting for a total explained variance of 73.8%.ConclusionThe functional impairments due to migraine chronification are primarily concentrated in the multisensory integration-related brain regions. Additionally, the rsFC of SPG with MOG can predict the frequency of migraine and the degree of vestibular dysfunction. Therefore, these neuroimaging features could be potential mechanisms and therapeutic targets for developing vestibular dysfunction in migraine.</p

Data_Sheet_1_Circulating metabolites and depression: a bidirectional Mendelian randomization.docx

BackgroundStudies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.MethodsIn this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and “leave-one-out” methods.ResultsApolipoprotein A-I (OR 0.990, 95% CI 981–0.999) and glutamine (OR 0.985, 95% CI 0.972–0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009–1.034), glycoproteins (OR 1.005, 95% CI 1.000–1.009), isoleucine (OR 1.013, 95% CI 1.002–1.024), and urea (OR 1.020, 95% CI 1.000–1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.ConclusionIn this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.</p

Table_2_Circulating metabolites and depression: a bidirectional Mendelian randomization.XLSX

BackgroundStudies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.MethodsIn this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and “leave-one-out” methods.ResultsApolipoprotein A-I (OR 0.990, 95% CI 981–0.999) and glutamine (OR 0.985, 95% CI 0.972–0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009–1.034), glycoproteins (OR 1.005, 95% CI 1.000–1.009), isoleucine (OR 1.013, 95% CI 1.002–1.024), and urea (OR 1.020, 95% CI 1.000–1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.ConclusionIn this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.</p

Table_1_Silicon Improves Rice Salinity Resistance by Alleviating Ionic Toxicity and Osmotic Constraint in an Organ-Specific Pattern.DOCX

Salinity stress severely inhibits the growth of plant via ionic toxicity and osmotic constraint. Exogenous silicon (Si) can alleviate salinity stress, but the mechanisms behind remain unclear. To investigate the role of Si in alleviating ionic and osmotic components of salinity, rice (Oryza sativa L.) seedlings were grown hydroponically in iso-osmotic stress conditions developed from NaCl or polyethylene glycol (PEG). The effects of Si on the growth of shoot and root of rice under salinity and PEG-derived osmotic stress were evaluated and further compared using principal coordinate analysis (PCoA). We also analyzed the concentrations of Na, K, and compatible osmolytes, tissue sap osmotic potential, antioxidant enzymes activities, and the expression of aquaporin genes. Generally, Si significantly promoted shoot and root growth in rice exposed to both NaCl and PEG. PCoA shows that the Si-induced distance change under NaCl treatment was larger than that under PEG treatment in the shoot, while the Si-induced distance changes under NaCl and PEG treatments were at an equal level in the root. Under salinity, Si decreased Na concentration and Na/K ratio in the shoot but not in the root. However, Si decreased net Na uptake and increased root Na accumulation content. Osmotic potential was increased in the shoot but decreased in the root by Si addition. Si decreased soluble sugar and proline concentrations in the shoot but increased soluble sugar and soluble protein concentrations in the root. Besides, Si promoted shoot transpiration rate and root morphological traits. Although both NaCl and PEG treatments upregulated aquaporin gene expression, Si addition maintained the expression of OsPIPs under NaCl and PEG treatments at same levels as control treatment. Furthermore, Si alleviated oxidative damages under both NaCl and PEG by regulating antioxidant enzyme activities. In summary, our results show that Si improves salt stress tolerance in rice by alleviating ionic toxicity and osmotic constraint in an organ-specific pattern. Si ameliorates ionic toxicity by decreasing Na uptake and increasing root Na reservation. Si alleviates osmotic constraint by regulating root morphological traits and root osmotic potential but not aquaporin gene expression for water uptake, and promoting transpiration force but not osmotic force in shoot for root-to-shoot water transport.</p

Characterization of Cellulase Secretion and Cre1-Mediated Carbon Source Repression in the Potential Lignocellulose-Degrading Strain <i>Trichoderma asperellum</i> T-1

<div><p><i>Trichoderma asperellum</i>, a traditional bio-control species, was demonstrated to be an excellent candidate for lignocellulose degradation in this work. Comparing to the representatively industrial strain of <i>Trichoderma reesei</i>QM6a, <i>T. asperellum</i> T-1 showed more robust growth, stronger spore production, faster secretion of lignocellulose-decomposing enzymes and better pH tolerance. The reducing sugar released by strain T-1 on the second day of fermentation was 87% higher than that of strain QM6a, although the maximum reducing sugar yield and the cellulase production persistence of the strain T-1 were lower. Our experiment found that the cellulase secretion was strongly inhibited by glucose, suggesting the existence of carbon source repression pathway in <i>T. asperellum</i> T-1. The inhibiting effect was enhanced with an increase in glucose concentration and was closely related to mycelium growth. SDS-PAGE and secondary mass-spectrum identification confirmed that the expression of endo-1,4-β-xylanase I in <i>T. asperellum</i> T-1 was down-regulated when glucose was added. The factor Cre1, which plays an important role in the down-regulation of the endo-1,4-β-xylanase I gene, was investigated by bioinformatics methods. The protein structure of Cre1, analyzed using multiple protein sequence alignment, indicates the existence of the Zn-fingers domain. Then, the binding sites of Cre1 on the endo-1,4-β-xylanase I gene promoter were further elucidated. This study is the first report about Cre1-mediated carbon repression in the bio-control strain <i>T. asperellum</i> T-1. All of the above results provided good references for better understanding <i>T. asperellum</i> T-1 and improving its application for lignocellulose degradation.</p></div

SDS-PAGE of fermented supernatant representing the protein expression differences when different concentrations of glucose were added at 0 h (a), 36 h and 60 h (b).

<p>SDS-PAGE of fermented supernatant representing the protein expression differences when different concentrations of glucose were added at 0 h (a), 36 h and 60 h (b).</p

Growth comparison of <i>T. asperellum</i> T-1 (right side in a; b; c) and <i>T. reesei</i> QM6a (left side in a; b; c) on PDA both on the obverse side and the reverse side of the plates.

<p>(a) Cultivation for 1 day; (b) Cultivation for 2 days; (c) Cultivation for 5 days.</p

Biomass and glucose consumption when different concentrations of glucose were used as the carbon sources.

<p>(Biomass: 0.5%: black triangle up; 1.0%: black square; 1.5%: black diamond; 2.0%: black hex; glucose consumption: 0.5%: dotted; 1.0%: short-short; 1.5%: dash-dot; 2.0%: long dash). Error bars denote standard deviations from the mean values of triplicate measurements (n = 3).</p

Cellulase production comparison of <i>T. asperellum</i> T-1 and <i>T. reesei</i> with wheat straw as carbon source, expressed as the concentration of reducing sugar released from the substrate by cellulase in the enzyme reaction system.

<p>(a) Filter paper activity (FPA) of <i>T. asperellum</i> T-1 (black circle) and <i>T. reesei</i> (diamond); (b) CMCase activity (endoglucanase activity) of <i>T. asperellum</i> T-1 (black circle) and <i>T. reesei</i> (diamond). Error bars denote standard deviations from the mean values of triplicate measurements (n = 3).</p