The maize PLASTID TERMINAL OXIDASE (PTOX) locus controls the carotenoid content of kernels.

Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.

An online soft sensor method for biochemical reaction process based on JS-ISSA-XGBoost.

BACKGROUND: A method combining offline techniques and the just-in-time learning strategy (JITL) is proposed, because the biochemical reaction process often encounters changing features and parameters over time. METHODS: Firstly, multiple sub-databases in the fermentation process are constructed offline by an improved fuzzy C-means algorithm and the sample data are adaptively pruned by a similarity query threshold. Secondly, an improved eXtreme Gradient Boosting (XGBoost) method is used on the online modeling stage to build soft sensor models, and the multi-similarity-driven just-in-time learning strategy is used to increase the diversity of the model. Finally, to improve the generalization of the whole algorithm, the output of the base learner is fused by an improved Stacking integration model and then the predictive output is performed. RESULTS: Applying the constructed soft sensor model to the problem of predicting cell concentration and product concentration in Pichia pastoris fermentation process. The experimental results show that the root mean square error of the cell concentration is 0.0260, the coefficient of determination is 0.9945, the root mean square error of the product concentration is 2.6688, and the coefficient of determination is 0.9970. It shows that the proposed method has the advantages of timely prediction and high prediction accuracy, which validates the effectiveness and practicality of the method. CONCLUSION: The JS-ISSA-XGBoost is an extensive and excellent soft measurement model that meets the practical needs for real-time monitoring of parameters and prediction of control in biochemical reactions.

White and green striate leaves 1, predicted to encode a 16S rRNA processing protein, plays a critical role in the processing of chloroplast ribosomes in maize (Zea mays L.).

Ribosomes play a crucial role in protein biosynthesis and are linked to plant growth and development. The RimM protein has been shown to be involved in the maturation of 30S ribosomal subunits, but its exact function in plants is still unknown. In this study, we discovered a maize mutant with white and green striate leaves (wgsl1) and reduced chlorophyll content. Genetic analysis showed that the wgsl1 mutation was recessive and controlled by a single nuclear gene. Map-based cloning of ZmWGSL1 identified a base substitution (G to A) that generated a missense mutation within the Zm00001d039036 gene in the wgsl1 mutant. Zm00001d039036 encodes a 16S rRNA processing protein containing the RimM motif. Further analysis of transcriptomic data showed that the transcript levels of many ribosomal proteins involved in the small and big ribosomal subunits were dramatically up-regulated in the wgsl1 mutant. Moreover, the level of ribosomal multimers was decreased. This suggests that ZmWGSL1 plays a crucial role in the maturation of the ribosome, leading to abnormal plant growth and development. In addition, subcellular localization results indicate that WGSL1 is localized in chloroplasts. Therefore, we suggest that WGSL1 is a nuclear-encoded protein, is transported to the chloroplast to drive functions, and affects the processing of ribosomes in the chloroplast. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01407-y.

A novel aminated lignin/geopolymer supported with Fe nanoparticles for removing Cr(VI) and naphthalene: Intermediates promoting the reduction of Cr(VI).

A novel, inexpensive and eco-friendly aminated lignin/geopolymer supported with Fe nanoparticles (Fe@N-L-GM) composite was successfully synthesized using kaolin and lignin as the major precursors. The prepared Fe@N-L-GM had larger specific surface area, rich oxygen-containing and nitrogen-containing functional groups, greater electron transfer ability and interconnective porous structure. The Fe@N-L-GM could be employed as the adsorbent of Cr(VI) and the activator of potassium peroxymonosulfate (PMS) for treatment of Cr(VI) and naphthalene (NAP) in wastewater. The adsorption and degradation results indicated that the maximum adsorption capacity of Cr(VI) could reach 65.83 mg g-1, whereas the maximum NAP degradation efficiency could reach 97.81 %. The adsorbed Cr(VI) was mostly converted to the low toxic Cr(III) through the reduction of electron donors such as Fe(II), amino and hydroxyl groups. The quenching experiment results confirmed that ·OH might be the crucial ROSs in mediating NAP degradation. In the simultaneous removal experiment of Cr(VI) and NAP, the Cr(VI) removal rate was significantly improved in the presence of NAP, while phenol as the degradation intermediate of NAP might be the main substance for promoting the reduction of Cr(VI). This work provided the theoretical foundation and a new type of material for the simultaneous removal of heavy metal and persistent organic pollutants (POPs).

Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate.

Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of ß-CD derivatives; (ii) methods for investigating the host-guest inclusion behavior between AC and ß-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of ß-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of ß-CD derivatives require 3-5 d of work. The photoirradiation of AC with ß-CD derivatives can be done within 1 h. The product analysis requires 5 h.

A low-cost and eco-friendly powder catalyst: Iron and copper nanoparticles supported on biochar/geopolymer for activating potassium peroxymonosulfate to degrade naphthalene in water and soil.

A low-cost and environment-friendly biochar/geopolymer composite loaded with Fe and Cu nanoparticles (Fe-Cu@BC-GM) was prepared by impregnation-calcination using lignin and kaolin as precursors. SEM, FTIR and XRD analysis suggested that the Fe-Cu@BC-GM had a certain pore structure, rich functional groups and stable crystal structure. The obtained Fe-Cu@BC-GM was used as the catalyst of potassium peroxymonosulfate (PMS) for remediation of wastewater and soil polluted by naphthalene (NAP). Experimental results indicated that Fe-Cu@BC-GM exhibited outstanding catalytic performance, and the maximum degradation rate of NAP in water and soil reached 98.35% and 67.98% within 120 min, respectively. The XPS measurement confirmed the presence of successive Fe (Ⅲ)/Fe (Ⅱ) and Cu(Ⅱ)/Cu(Ⅰ) redox pairs cycles on the surface of Fe-Cu@BC-GM, which made Fe (Ⅲ) and Cu(Ⅰ) continuously generated Fe (Ⅱ) activating PMS to produce SO4·- and ·OH for the degradation of NAP. The effects of Fe-Cu@BC-GM/PMS system on plant toxicity were evaluated by analyzing the degradation intermediates and bioassay of mung bean. It was proved that the Fe-Cu@BC-GM/PMS system could degrade NAP into less toxic intermediates, and the seed germination rate, root and stem length of mung bean after soil remediation were not notably different from those of the uncontaminated soil. This work opened new prospect for the application of geopolymer in degradation of persistent organic pollutants (POPs) and provided a cost-effective option for the remediation of the persistent organic pollutants contaminated water and soil.

The Importance of a Genome-Wide Association Analysis in the Study of Alternative Splicing Mutations in Plants with a Special Focus on Maize.

Alternative splicing is an important mechanism for regulating gene expressions at the post-transcriptional level. In eukaryotes, the genes are transcribed in the nucleus to produce pre-mRNAs and alternative splicing can splice a pre-mRNA to eventually form multiple different mature mRNAs, greatly increasing the number of genes and protein diversity. Alternative splicing is involved in the regulation of various plant life activities, especially the response of plants to abiotic stresses and is also an important process of plant growth and development. This review aims to clarify the usefulness of a genome-wide association analysis in the study of alternatively spliced variants by summarizing the application of alternative splicing, genome-wide association analyses and genome-wide association analyses in alternative splicing, as well as summarizing the related research progress.

Core-shell structural nitrogen-doped carbon foam loaded with nano zero-valent iron for simultaneous remediation of Cd (II) and NAP in water and soil: Kinetics, mechanism, and environmental evaluation.

An economical, efficient, and environmentally friendly technology was developed for simultaneous remediation of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in soil and water. In this study, using pinecones powder as the precursor, the core-shell structural nitrogen-doped carbon foam loaded with nano zero-valent iron (nZVI@NCF) was synthesized through Mannich reaction and high-temperature carbon reduction. The nZVI@NCF was applied as the adsorbent and catalyst to simultaneously remediate the composite pollutants of Cd (II) and naphthalene (NAP). Under the optimal conditions, the adsorption capacity of Cd (II) in water and soil were 13.9 mg·g-1 and 1.97 mg·g-1, respectively, and the adsorption process conformed to the pseudo-second-order kinetic model. The degradation rates of NAP in water (10 mg·L-1) reached almost 100% as well as it could reach 59.12% in soil (10 mg·kg-1). In addition, it was proved that the presence of NAP could compete with Cd (II) for the active sites on the surface of the material to inhibit the adsorption of Cd (II), while the co-existence of Cd (II) could improve the degradation of NAP by the nZVI@NCF/PMS system due to the nZVI-Cd bimetallic effect and the pro-oxidant effect of Cd (II) promoting the generation of ROS. The free radical quenching experiment revealed that the generated ·O2- was the main substance that mediated the redox of nZVI/Fe2+/Fe3+ to oxidative NAP during the degradation process. Furthermore, the results of the phytotoxicity test demonstrated that the nZVI@NCF/PMS system could effectively remediate the soil co-contaminated with Cd (II) and NAP as well as improve the soil environment quality. This research will provide new materials and potential technologies for the efficient treatment of the composite pollutants in the environment.

Identification and Fine Mapping of the Recessive Gene BK-5, Which Affects Cell Wall Biosynthesis and Plant Brittleness in Maize.

The cellulose of the plant cell wall indirectly affects the cell shape and straw stiffness of the plant. Here, the novel brittleness mutant brittle stalk-5 (bk-5) of the maize inbred line RP125 was characterized. We found that the mutant displayed brittleness of the stalk and even the whole plant, and that the brittleness phenotype existed during the whole growth period from germination to senescence. The compressive strength was reduced, the cell wall was thinner, and the cellulose content was decreased compared to that of the wild type. Genetic analysis and map-based cloning indicated that bk-5 was controlled by a single recessive nuclear gene and that it was located in a 90.2-Kb region on chromosome 3 that covers three open reading frames (ORFs). Sequence analysis revealed a single non-synonymous missense mutation, T-to-A, in the last exon of Zm00001d043477 (B73: version 4, named BK-5) that caused the 951th amino acid to go from leucine to histidine. BK-5 encodes a cellulose synthase catalytic subunit (CesA), which is involved with cellulose synthesis. We found that BK-5 was constitutively expressed in all tissues of the germinating stage and silking stage, and highly expressed in the leaf, auricula, and root of the silking stage and the 2-cm root and bud of the germinating stage. We found that BK-5 mainly localized to the Golgi apparatus, suggesting that the protein might move to the plasma membrane with the aid of Golgi in maize. According to RNA-seq data, bk-5 had more downregulated genes than upregulated genes, and many of the downregulated genes were enzymes and transcription factors related to cellulose, hemicellulose, and lignin biosynthesis of the secondary cell wall. The other differentially expressed genes were related to metabolic and cellular processes, and were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and the plant-pathogen interaction pathway. Taken together, we propose that the mutation of gene BK-5 causes the brittle stalk phenotype and provides important insights into the regulatory mechanism of cellulose biosynthesis and cell wall development in maize.

Iron nanoparticles supported on N-doped carbon foam with honeycomb microstructure: An efficient potassium peroxymonosulfate activator for the degradation of fluoranthene in water and soil.

A promising technology was developed for the remediation of fluoranthene (FLT) contaminated water and soil. Specifically, iron nanoparticles supported on N-doped carbon foam (Fe@CF-N) was synthesized by in-situ impregnation and a unique calcination process using pine cone as the precursor. The obtained Fe@CF-N was used as an activator of potassium peroxymonosulfate (PMS) to degrade FLT in water and soil. According to experimental results, Fe@CF-N had a three-dimensional network structure with a large specific surface area of 249.0 m2 g-1, displaying excellent catalytic performance. The maximum removal efficiency of FLT in water and soil reached 81.83% and 78.12% within 180 min, respectively. After four consecutive degradation cycles, the removal efficiency of FLT in water was still 55%. Electron spin resonance (ESR) measurements showed that hydroxyl radicals (·OH), sulfate radical (SO4-·) and 1O2 were the major reactive oxygen species (ROS). A series of low molecular weight intermediates were generated during the FLT degradation progress, such as C6H6O3 and C3H8O2. The effect of Fe@CF-N/PMS system on the phytotoxicity was evaluated via bioassay based on peas. The results indicated that seed germination rate and root shoot elongation of remediated soil by Fe@CF-N/PMS system were not significantly different from those of noncontaminated soil. This study provided a cost-effective remediation option for PAHs contaminated water and soil.

Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement.

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.

Plant metabolomics integrated with transcriptomics and rhizospheric bacterial community indicates the mitigation effects of Klebsiella oxytoca P620 on p-hydroxybenzoic acid stress in cucumber.

Accumulation of p-hydroxybenzoic acid (PHBA) in soil causes autotoxicity stress in cucumber. When the stress is mitigated by PHBA-degrading bacteria, plant metabolites have not been detected. To explore mechanisms underlining the mitigation, plant metabolites have not been combined with rhizospheric microbes, antioxidant and soil enzymes. In this study, a strain P620 of Klebsiella decomposed PHBA to acetyl CoA. Cucumber was sown into soil supplemented with P620 and/or PHBA. After addition with P620, P620 colonization and the enriched bacterial genera were observed in rhizosphere. Compared to PHBA stress alone, the combination of P620 application and PHBA stress improved plant growth, decreased PHBA concentration in soil, and increased the activities of five soil enzymes and eight antioxidant enzymes in leaves. Metabolomic and transcriptomic analysis highlighted that P620 application decreased the intensities of MAG(18:3) isomer 4, MAG(18:3) isomer 2, lysoPC 18:3 (2n isomer), 2'-deoxyadenosine-5'-monophosphate, pyridoxine, and glucarate O-phosphoric acid in PHBA-stressed leaves and down-regulated the expression of genes related to these metabolites. We propose a mechanism that P620 application alters microbial communities in PHBA-contaminated soil. Thus, the application reduces PHBA concentration in soil, activates antioxidant and soil enzymes, and also influences metabolites in leaves by affecting plant transcriptome, mitigating PHBA stress in cucumber.

Enhanced removal of Cd (II) from aqueous solution by EDTA functionalized three-dimensional magnetic nitrogen-doped porous carbon.

In this paper, three-dimensional magnetic nitrogen-doped porous carbon modified by EDTA (N-MPC-EDTA) was successfully prepared by two-step method with lignin as the precursor, and was used for the removal of Cd (II). The 3D adsorbents were characterized by SEM, TEM, BET, XRD, XPS, Zeta potential, and element mapping analysis techniques, and the performance of the materials was tested by the batch adsorption method. The influence of experimental parameters such as contact time and pH value on the adsorption capacity of N-MPC-EDTA on Cd (II) was studied. Under the optimal conditions, the equilibrium adsorption capacity of Cd (II) was 43.68 mg∙ L-1 and the adsorption equilibrium was quickly reached within 45 min. A possible adsorption mechanism was proposed, in which the chelation of EDTA as well as the electrostatic attraction of hydroxyl, carboxyl, and nitrogen-containing functional groups dominated the adsorption of Cd (II). The adsorption kinetics and isotherm data fitted well with the pseudo-second-order kinetic model and Freundlich model, respectively. In addition, the good regeneration performance suggested that N-MPC-EDTA will have a broad application prospect in water treatment.

Comprehensive transcriptome and proteome analyses reveal a novel sodium chloride responsive gene network in maize seed tissues during germination.

Germination is a plant developmental process by which radicle of mature seeds start to penetrate surrounding barriers for seedling establishment and multiple environmental factors have been shown to affect it. Little is known how high salinity affects seed germination of C4 plant, Zea mays. Preliminary germination assay suggested that isolated embryo alone was able to germinate under 200 mM NaCl treatment, whereas the intact seeds were highly repressed. We hypothesized that maize endosperm may function in perception and transduction of salt signal to surrounding tissues such as embryo, showing a completely different response to that in Arabidopsis. Since salt response involves ABA, we analysed in vivo ABA distribution and quantity and the result demonstrated that ABA level in isolated embryo under NaCl treatment failed to increase in comparison with the water control, suggesting that the elevation of ABA level is an endosperm dependent process. Subsequently, by using advanced profiling techniques such as RNA sequencing and SWATH-MS-based quantitative proteomics, we found substantial differences in post-transcriptional and translational changes between salt-treated embryo and endosperm. In summary, our results indicate that these regulatory mechanisms, such as alternative splicing, are likely to mediate early responses to salt stress during maize seed germination.

Nitrate deficiency induces differential endocytosis in roots through NRT1.1.

Roots grow asymmetrically, sometimes helically, around their growth direction likely to facilitate environmental sensing. We recently demonstrated that nitrate deficiency induces root coiling on horizontal surface through nitrate transporter/sensor NRT1.1 and PIN2- and AUX-mediated polar auxin transport. Here, we show that nitrate deficiency or NRT1.1 loss-of-function induces differential distribution of PIN2 between the future concave and concave sides in root epidermal cells. Treatment with pharmacological drugs suggests that enhanced endocytosis at the future convex side leads to reduced plasma membrane (PM) association of PIN2. A reduction of PIN2 at the PM would maintain a low auxin response to further enhance endocytosis at the convex side, leading to root coiling.

Resolving Isomeric Glycopeptide Glycoforms with Hydrophilic Interaction Chromatography (HILIC).

The ability to resolve glycans while attached to tryptic peptides would greatly facilitate glycoproteomics, as this would enable site-specific glycan characterization. Peptide/glycopeptide separations are typically performed using reversed-phase liquid chromatography (RPLC), where retention is driven by hydrophobic interaction. As the hydrophilic glycans do not interact significantly with the RPLC stationary phase, it is difficult to resolve glycopeptides that differ only in their glycan structure, even when these differences are large. Alternatively, glycans interact extensively with the stationary phases used in hydrophilic interaction chromatography (HILIC), and consequently, differences in glycan structure have profound chromatographic shifts in this chromatographic mode. Here, we evaluate HILIC for the separation of isomeric glycopeptide mixtures that have the same peptide backbone but isomeric glycans. Hydrophilic functional groups on both the peptide and the glycan interact with the HILIC stationary phase, and thus, changes to either of these moieties can alter the chromatographic behavior of a glycopeptide. The interactive processes permit glycopeptides to be resolved from each other based on differences in their amino acid sequences and/or their attached glycans. The separations of glycans in HILIC are sufficient to permit resolution of isomeric N-glycan structures, such as sialylated N-glycan isomers differing in α2-3 and α2-6 linkages, while these glycans remain attached to peptides.

Fine mapping a major QTL for kernel number per row under different phosphorus regimes in maize (Zea mays L.).

Phosphorus (P) is one of the essential macronutrients for plant growth and development. Grain yield is the primary trait of interest in maize breeding programs. Maize grain yield and yield-related traits are seriously affected by P deficiency. Kernel number per row (KN), as one of the major components of grain yield, has attracted the attention of more and more breeders. In our previous study, one major QTL (named qKN), controlling KN under different P regimes was mapped to the interval between molecular markers bnlg1360 and umc1645 on chromosome 10 using a F 2:3 population derived from the cross between maize inbreds 178 and 5,003 (107). In order to understand its genetic basis, we developed a population of near isogenic lines (NILs) and two P regimes were used to fine map and characterize qKN. The QTL qKN was finally localized in a region of ~480 kb. A single qKN allele of inbred 178 increased KN by 6.08-10.76 % in the 5,003 (107) background; qKN acted in a partially dominant manner. Our results will be instrumental for the future identification and isolation of the candidate gene underlying qKN. The tightly linked molecular markers that we developed for qKN will be useful in maize breeding programs for improving KN applying the marker-assisted selection.

[Cognitive behavioral therapy for depression in advanced schistosomiasis patients].

OBJECTIVE: To evaluate the efficacy of cognitive behavioral therapy for depression in advanced schistosomiasis patients. METHODS: A total of 60 advanced schistosomiasis patients with major depressive disorder were divided into a combination therapy group (30 cases) who received sertraline plus cognitive behavior therapy and a monotherapy group (30 cases) who received sertraline only. Before the treatment and at the 1st, 2nd, 4th, 8th week after the treatment, the efficacy and safety were assessed with the HAMD17 item score and the related factor points and TESS. The effective rate, side effect rate and relapse rate in six months were calculated and compared between the two groups. RESULTS: At the end of 8th week after the treatment, the total scores of HAMD, factor scores of cognitive impairment, retardation factor scores and sleep disturbance factor scores in the 2 groups were statistically decreased compared with those before the treatment (P < 0.05 or P < 0.01). The factor scores in the combined therapy group were lower than those in the monotherapy group. The effective rate in the combination therapy group was 86.7% (26/30), and it was significantly higher than that in the monotherapy group (56.7%, 17/30), (chi2 = 6.65, P < 0.05). The doses of the drug were lower in the combination therapy group than those in the monotherapy group (t = 2.25, P < 0.05). Within six months, the relapse rate was 13.3% in the combination therapy group, and it was significantly lower than that in the monotherapy group (46.7%) (chi2 = 7.937, P < 0.025). The side effect rate was 23.3% in the combination therapy group and that was 26.7% in the monotherapy group, and there was no statistically significant difference between the two groups (P > 0.05). CONCLUSION: The combination therapy (drug combined with cognitive behavioral therapy) is effective in advanced schistosomiasis patients with depression, and it also can reduce the amount of medication and the relapse.