Identification of a diagnostic model and molecular subtypes of major depressive disorder based on endoplasmic reticulum stress-related genes

SubjectMajor depressive disorder (MDD) negatively affects patients’ behaviours and daily lives. Due to the high heterogeneity and complex pathological features of MDD, its diagnosis remains challenging. Evidence suggests that endoplasmic reticulum stress (ERS) is involved in the pathogenesis of MDD; however, relevant diagnostic markers have not been well studied. This study aimed to screen for ERS genes with potential diagnostic value in MDD.MethodsGene expression data on MDD samples were downloaded from the GEO database, and ERS-related genes were obtained from the GeneCards and MSigDB databases. Differentially expressed genes (DEGs) in MDD patients and healthy subjects were identified and then integrated with ERS genes. ERS diagnostic model and nomogram were developed based on biomarkers screened using the LASSO method. The diagnostic performance of this model was evaluated. ERS-associated subtypes were identified. CIBERSORT and GSEA were used to explore the differences between the different subtypes. Finally, WGCNA was performed to identify hub genes related to the subtypes.ResultsA diagnostic model was developed based on seven ERS genes: KCNE1, PDIA4, STAU1, TMED4, MGST1, RCN1, and SHC1. The validation analysis showed that this model had a good diagnostic performance. KCNE1 expression was positively correlated with M0 macrophages and negatively correlated with resting CD4+ memory T cells. Two subtypes (SubA and SubB) were identified, and these two subtypes showed different ER score. The SubB group showed higher immune infiltration than the SubA group. Finally, NCF4, NCF2, CSF3R, and FPR2 were identified as hub genes associated with ERS molecular subtypes.ConclusionOur current study provides novel diagnostic biomarkers for MDD from an ERS perspective, and these findings further facilitate the use of precision medicine in MDD

In Vitro Assessment of Cytochrome P450 2C19 Potential of Naoxintong

The effects of Buchang Naoxintong Capsules (BNCs) on S-mephenytoin 4′-hydroxylation activities in human liver microsomes in vitro were assessed. Human liver microsome was prepared by different ultracentrifugation. Human liver microsome incubation experiment was carried out to assay BNC on S-mephenytoin 4′-hydroxylation activities. The 4′-hydroxylation of S-mephenytoin, a representative substrate toward CYP2C19, was increased by phenytoin sodium (positive control). After the incubation, the metabolites of the substrates (4′-OH-mephenytoin) were determined by HPLC. Results showed that both phenytoin sodium and BNC showed obvious increase effect on CYP2C19. The enzymatic reaction of BNC was observed with concentrations ranging from 5 μg/mL to 250 μg/mL. Compared to blank, the increase effect of BNC showed significant difference from the beginning of concentration of 150 μg/mL (P < 0.001). The conclusion was that BNC showed obvious increase effect on the catalytic activities of drug-metabolising CYP2C19 enzyme

Mapping the spectral phase of isolated attosecond pulses by extreme-ultraviolet emission spectrum

An all-optical method is proposed for the measurement of the spectral phase of isolated attosecond pulses. The technique is based on the generation of extreme-ultraviolet (XUV) radiation in a gas by the combination of an attosecond pulse and a strong infrared (IR) pulse with controlled electric field. By using a full quantum simulation, we demonstrate that, for particular temporal delays between the two pulses, the IR field can drive back to the parent ions the photoelectrons generated by the attosecond pulse, thus leading to the generation of XUV photons. It is found that the generated XUV spectrum is notably sensitive to the chirp of the attosecond pulse, which can then be reliably retrieved. A classical quantum-path analysis is further used to quantitatively explain the main features exhibited in the XUV emission

Identification of Major QTLs Associated With First Pod Height and Candidate Gene Mining in Soybean

First pod height (FPH) is a quantitative trait in soybean [Glycine max (L.) Merr.] that affects mechanized harvesting. A compatible combination of the FPH and the mechanized harvester is required to ensure that the soybean is efficiently harvested. In this study, 147 recombinant inbred lines, which were derived from a cross between ‘Dongnong594’ and ‘Charleston’ over 8 years, were used to identify the major quantitative trait loci (QTLs) associated with FPH. Using a composite interval mapping method with WinQTLCart (version 2.5), 11 major QTLs were identified. They were distributed on five soybean chromosomes, and 90 pairs of QTLs showed significant epistatic associates with FPH. Of these, 3 were main QTL × main QTL interactions, and 12 were main QTL × non-main QTL interactions. A KEGG gene annotation of the 11 major QTL intervals revealed 8 candidate genes related to plant growth, appearing in the pathways K14486 (auxin response factor 9), K14498 (serine/threonine-protein kinase), and K13946 (transmembrane amino acid transporter family protein), and 7 candidate genes had high expression levels in the soybean stems. These results will aid in building a foundation for the fine mapping of the QTLs related to FPH and marker-assisted selection for breeding in soybean

Soybean Breeding on Seed Composition Trait

Soybean is a most important crop providing edible oil and plant protein source for human beings, in addition to animal feed because of high protein and oil content. This review summarized the progresses in the QTL mapping, candidate gene cloning and functional analysis and also the regulation of soybean oil and seed storage protein accumulation. Furthermore, as soybean genome has been sequenced and released, prospects of multiple omics and advanced biotechnology should be combined and applied for further refine research and high-quality breeding

CNS-LAND score: predicting early neurological deterioration after intravenous thrombolysis based on systemic responses and injury

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase &gt;4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT

Fine mapping and candidate gene analysis of proportion of four-seed pods by soybean CSSLs

Soybean yield, as one of the most important and consistent breeding goals, can be greatly affected by the proportion of four-seed pods (PoFSP). In this study, QTL mapping was performed by PoFSP data and BLUE (Best Linear Unbiased Estimator) value of the chromosome segment substitution line population (CSSLs) constructed previously by the laboratory from 2016 to 2018, and phenotype-based bulked segregant analysis (BSA) was performed using the plant lines with PoFSP extreme phenotype. Totally, 5 ICIM QTLs were repeatedly detected, and 6 BSA QTLs were identified in CSSLs. For QTL (qPoFSP13-1) repeated in ICIM and BSA results, the secondary segregation populations were constructed for fine mapping and the interval was reduced to 100Kb. The mapping results showed that the QTL had an additive effect of gain from wild parents. A total of 14 genes were annotated in the delimited interval by fine mapping. Sequence analysis showed that all 14 genes had genetic variation in promoter region or CDS region. The qRT−PCR results showed that a total of 5 candidate genes were differentially expressed between the plant lines having antagonistic extreme phenotype (High PoFSP &gt; 35.92%, low PoFSP&lt; 17.56%). The results of haplotype analysis showed that all five genes had two or more major haplotypes in the resource population. Significant analysis of phenotypic differences between major haplotypes showed all five candidate genes had haplotype differences. And the genotypes of the major haplotypes with relatively high PoFSP of each gene were similar to those of wild soybean. The results of this study were of great significance to the study of candidate genes affecting soybean PoFSP, and provided a basis for the study of molecular marker-assisted selection (MAS) breeding and four-seed pods domestication

A proteogenomic analysis of Shigella flexneri using 2D LC-MALDI TOF/TOF

<p>Abstract</p> <p>Background</p> <p>New strategies for high-throughput sequencing are constantly appearing, leading to a great increase in the number of completely sequenced genomes. Unfortunately, computational genome annotation is out of step with this progress. Thus, the accurate annotation of these genomes has become a bottleneck of knowledge acquisition.</p> <p>Results</p> <p>We exploited a proteogenomic approach to improve conventional genome annotation by integrating proteomic data with genomic information. Using <it>Shigella flexneri </it>2a as a model, we identified total 823 proteins, including 187 hypothetical proteins. Among them, three annotated ORFs were extended upstream through comprehensive analysis against an in-house N-terminal extension database. Two genes, which could not be translated to their full length because of stop codon 'mutations' induced by genome sequencing errors, were revised and annotated as fully functional genes. Above all, seven new ORFs were discovered, which were not predicted in <it>S. flexneri </it>2a str.301 by any other annotation approaches. The transcripts of four novel ORFs were confirmed by RT-PCR assay. Additionally, most of these novel ORFs were overlapping genes, some even nested within the coding region of other known genes.</p> <p>Conclusions</p> <p>Our findings demonstrate that current <it>Shigella </it>genome annotation methods are not perfect and need to be improved. Apart from the validation of predicted genes at the protein level, the additional features of proteogenomic tools include revision of annotation errors and discovery of novel ORFs. The complementary dataset could provide more targets for those interested in <it>Shigella </it>to perform functional studies.</p

Combining blue native polyacrylamide gel electrophoresis with liquid chromatography tandem mass spectrometry as an effective strategy for analyzing potential membrane protein complexes of Mycobacterium bovis bacillus Calmette-Guérin

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is an infectious bacterial disease in humans caused primarily by <it>Mycobacterium tuberculosis</it>, and infects one-third of the world's total population. <it>Mycobacterium bovis </it>bacillus Calmette-Guérin (BCG) vaccine has been widely used to prevent tuberculosis worldwide since 1921. Membrane proteins play important roles in various cellular processes, and the protein-protein interactions involved in these processes may provide further information about molecular organization and cellular pathways. However, membrane proteins are notoriously under-represented by traditional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and little is known about mycobacterial membrane and membrane-associated protein complexes. Here we investigated <it>M. bovis </it>BCG by an alternative proteomic strategy coupling blue native PAGE to liquid chromatography tandem mass spectrometry (LC-MS/MS) to characterize potential protein-protein interactions in membrane fractions.</p> <p>Results</p> <p>Using this approach, we analyzed native molecular composition of protein complexes in BCG membrane fractions. As a result, 40 proteins (including 12 integral membrane proteins), which were organized in 9 different gel bands, were unambiguous identified. The proteins identified have been experimentally confirmed using 2-D SDS PAGE. We identified MmpL8 and four neighboring proteins that were involved in lipid transport complexes, and all subunits of ATP synthase complex in their monomeric states. Two phenolpthiocerol synthases and three arabinosyltransferases belonging to individual operons were obtained in different gel bands. Furthermore, two giant multifunctional enzymes, Pks7 and Pks8, and four mycobacterial Hsp family members were determined. Additionally, seven ribosomal proteins involved in polyribosome complex and two subunits of the succinate dehydrogenase complex were also found. Notablely, some proteins with high hydrophobicity or multiple transmembrane helixes were identified well in our work.</p> <p>Conclusions</p> <p>In this study, we utilized LC-MS/MS in combination with blue native PAGE to characterize modular components of multiprotein complexes in BCG membrane fractions. The results demonstrated that the proteomic strategy was a reliable and reproducible tool for analysis of BCG multiprotein complexes. The identification in our study may provide some evidence for further study of BCG protein interaction.</p