Identification of a Hypoxia-Related Signature as Candidate Detector for Schizophrenia Based on Genome-Wide Gene Expression.

INTRODUCTION: Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients. METHODS: GSE17612, GSE21935, and GSE53987 datasets, consisting of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patient. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores and patients in low-score groups if their hypoxia score was in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients. RESULTS: In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in the patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients. CONCLUSION: These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.

OsFBN7-OsKAS I module promotes formation of plastoglobules clusters in rice chloroplasts.

Plastoglobules (PGs) contiguous with the outer leaflets of thylakoid membranes regulate lipid metabolism, plastid developmental transitions, and responses to environmental stimuli. However, the function of OsFBN7, a PG-core fibrillin gene in rice, has not been elucidated. Using molecular genetics and physiobiochemical approaches, we observed that OsFBN7 overexpression promoted PG clustering in rice chloroplasts. OsFBN7 interacted with two KAS I enzymes, namely OsKAS Ia and OsKAS Ib, in rice chloroplasts. Lipidomic analysis of chloroplast subcompartments, including PGs in the OsFBN7 overexpression lines, confirmed that levels of diacylglycerol (DAG), a chloroplast lipid precursor and monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), the main chloroplast membrane lipids, were increased in PGs and chloroplasts. Furthermore, OsFBN7 enhanced the abundances of OsKAS Ia/Ib in planta and their stability under oxidative and heat stresses. In addition, RNA sequencing and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses showed that the expression of the DAG synthetase gene PAP1 and MGDG synthase gene MDG2 was upregulated by OsFBN7. In conclusion, this study proposes a new model in which OsFBN7 binds to OsKAS Ia/Ib in chloroplast and enhances their abundance and stability, thereby regulating the chloroplast and PG membrane lipids involved in the formation of PG clusters.

OsNAC74 affects grain protein content and various biological traits by regulating OsAAP6 expression in rice.

The grain protein content is an important quality trait in cereals, and the expression level of the OsAAP6 can significantly affect the grain protein content in rice. Through site-directed mutagenesis, we found that the position from -7 to -12 bp upstream of the transcription start site of the OsAAP6 was the functional variation site. By using the yeast single hybrid test, point-to-point in yeast, and the local surface plasmon resonance test, the OsNAC74 was screened and verified to be a regulator upstream of OsAAP6. The OsNAC74 is a constitutively expressed gene whose product is located on the cell membrane. The OsAAP6 and the genes related to the seed storage in the Osnac74 mutants were downregulated, and grain protein content was significantly reduced. In addition, OsNAC74 had a significant impact on quality traits such as grain chalkiness and gel consistency in rice. Although the Osnac74 mutant seeds were relatively small, the individual plant yield was not decreased. Therefore, OsNAC74 is an important regulatory factor with multiple biological functions. This study provides important information for the later use of OsNAC74 gene for molecular design and breeding in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01433-w.

OsClo5 functions as a transcriptional co-repressor by interacting with OsDi19-5 to negatively affect salt stress tolerance in rice seedlings.

Caleosins constitute a small protein family with one calcium-binding EF-hand motif. They are involved in the regulation of development and response to abiotic stress in plants. Nevertheless, how they impact salt stress tolerance in rice is largely unknown. Thereby, biochemical and molecular genetic experiments were carried out, and the results revealed that OsClo5 was able to bind calcium and phospholipids in vitro and localized in the nucleus and endoplasmic reticulum in rice protoplasts. At the germination and early seedlings stages, overexpression transgenic lines and T-DNA mutant lines exhibited reduced and increased tolerance to salt stress, respectively, compared with the wild-type. Yeast two-hybrid, bimolecular fluorescence complementation and in vitro pull-down assays demonstrated that the EF-hand motif of OsClo5 was essential for the interactions with itself and OsDi19-5. Yeast one-hybrid, electrophoretic migration shift and dual-luciferase reporter assays identified OsDi19-5 as a transcriptional repressor via the TACART cis-element in the promoters of two salt stress-related target genes, OsUSP and OsMST. In addition, OsClo5 enhanced the inhibitory effect of OsDi19-5 in the tobacco transient system, which was confirmed by qRT-PCR analysis in rice seedlings under salt stress. The collective results deepen the understanding of the molecular mechanism underlying the roles of caleosin in the salt stress response. These findings will also inform efforts to improve salt tolerance of rice.

[Meta-analysis on the Effects of Nitrogen Addition on Soil Organic Carbon Content in Terrestrial Ecosystems].

Several studies have demonstrated that the increased deposition of nitrogen(N) has significantly affected the content of soil organic carbon(SOC); however, the change significantly varies in different regions. In this study, Meta-analysis, Meta-regression, and linear regression were performed to systematically evaluate the effects of climate, soil properties, and field design factors on the responses of SOC to N addition based on 408 data points from 49 field experiments in China. The results revealed that the response of SOC to N addition was significantly positively correlated with the mean annual temperature(MAT) and mean annual precipitation(MAP) of the sample sites(P<0.05). In the regions with lower MAT(<3℃) or MAP(<500 mm), SOC significantly decreased after N addition. In the areas with higher MAT(>3℃) or MAP(>500 mm); however, SOC significantly increased. For soil properties, SOC significantly accumulated after N addition in the plots with a higher soil C:N ratio(>15) or acidic soil(pH<6.5) but less changed in the plots with a lower C:N ratio(≤ 15) or higher pH(≥ 6.5). For ecotype, after N addition, SOC decreased significantly in the grassland ecosystem(-5.34%) but less changed in the wetland ecosystem. SOC accumulated the most after N addition in the forest ecosystem(10.52%), particularly in the broad-leaved forest ecosystem(13.10%). Further analysis showed that the soil C:N ratio was the most important factor. For type of N application, the addition of ammonium nitrate or urea increased the SOC content significantly, but the effect of nitrate was not significant. In summary, when accurately evaluating, predicting, and analyzing the effects of N addition on SOC content, the effects of climatic characteristics and soil properties of sample sites and field design factors should be comprehensively considered.

Meta-analysis on the effects of nitrogen deposition on soil N2O flux in different habitats.

We carried out a meta-analysis to explore the effects of site characteristics (climatic factors and soil properties) and nitrogen (N) factors on soil nitrous oxide (N2O) flux after N addition based on 290 data from 66 field N addition experiments in China. The results showed that mean annual precipitation, mean annual temperature, ambient N deposition rate, and soil C/N of sites were positively correlated with the increases of N2O flux after N addition. Soil pH was negatively correlated with the increases of N2O flux after N addition. Furthermore, soils in wetland ecosystem were most sensitive to N addition, followed by forest ecosystem, and grassland showed the lowest sensitivity. Among all the site characteristics, soil pH and C/N were the most important factors driving the responses of N2O flux to N addition. Soil N2O flux increased the greatest after nitrate addition. The increase of N2O flux was similar after the addition of urea and ammonium, while N2O flux increased the least when ammonium nitrate was added. In summary, to accurately assess and predict the response of soil N2O flux to N deposition, the effects of site characteristics and N fertilizer types should be comprehensively considered.

Whiter matter abnormalities in medication-naive subjects with a single short-duration episode of major depressive disorder.

Convergent studies have implicated white matter abnormalities in the pathophysiology of major depressive disorder (MDD). In this study, diffusion tensor imaging (DTI) was used to examine white matter abnormalities in 23 single-episode, medication-naive MDD participants versus 21 healthy control participants. Voxel-based analysis was used to investigate whole brain white matter abnormalities in the MDD group. Fractional anisotropy was significantly lower and apparent diffusion coefficient was significantly higher in the right superior longitudinal fasciculus (SLF) within the frontal lobe, right middle frontal and left parietal white matter in the MDD group compared with the healthy group.

Frontal-subcortical volumetric deficits in single episode, medication-naïve depressed patients and the effects of 8 weeks fluoxetine treatment: a VBM-DARTEL study.

BACKGROUND: Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD). Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine. METHODS: 28 single episode, medication-naïve MDD participants and 28 healthy controls (HC) acquired the baseline high-resolution structural magnetic resonance imaging (sMRI) scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV) difference between groups was examined. RESULTS: Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected). Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected). No difference on GMV was detected between medication-naïve MDD group and treated MDD group. CONCLUSIONS: This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.