Neuroprotective effects of cordycepin on MPTP-induced Parkinson's disease mice via suppressing PI3K/AKT/mTOR and MAPK-mediated neuroinflammation.

Parkinson's disease (PD) is a prevalent progressive and multifactorial neurodegenerative disorder. Cordycepin is known to exhibit antitumor, anti-inflammatory, antioxidative stress, and neuroprotective effects; however, few studies have explored the neuroprotective mechanism of cordycepin in PD. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we investigated the impact of cordycepin on PD and its underlying molecular mechanisms. The findings indicated that cordycepin significantly mitigated MPTP-induced behavior disorder and neuroapoptosis, diminished the loss of dopaminergic neurons in the striatum-substantia nigra pathway, elevated striatal monoamine levels and its metabolites, and inhibited the polarization of microglia and the expression of pro-inflammatory factors. Subsequent proteomic and phosphoproteomic analyses revealed the involvement of the MAPK, mTOR, and PI3K/AKT signaling pathways in the protective mechanism of cordycepin. Cordycepin treatment inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the expression of autophagy proteins in the striatum and substantia nigra. We also demonstrated the in vivo inhibition of the ERK/JNK signaling pathway by cordycepin treatment. In summary, our investigation reveals that cordycepin exerts neuroprotective effects against PD by promoting autophagy and suppressing neuroinflammation and neuronal apoptosis by inhibiting the PI3K/AKT/mTOR and ERK/JNK signaling pathways. This finding highlights the favorable characteristics of cordycepin in neuroprotection and provides novel molecular insights into the neuroprotective role of natural products in PD.

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The main bioactive component of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) exerts protective effects against diseases such as neurodegenerative diseases and cancer. Therefore, this study investigated the effect of EGCG on the amelioration of neural damage in a chronic PD mouse model induced by α-synuclein preformed fibrils (α-syn-PFFs). A total of 20 C57BL/6J female mice were randomly divided into 3 groups: control group (saline, n = 6), model group (PFFs, n = 7), and prevention group (EGCG+PFFs, n = 7). A chronic PD mouse model was obtained by the administration of α-syn-PFFs by stereotaxic localization in the striatum. Behavioral tests were performed to evaluate PD-related anxiety-like behavior and motor impairments in the long-term PD progression. Tyrosine hydroxylase (TH) immuno-positive neurons and Ser129-phosphorylated α-syn (p-α-syn) were identified by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokines were measured by real-time quantitative PCR. EGCG pretreatment reduced anxiety-like behavior and motor impairments as revealed by the long-term behavioral test (2 weeks, 1 month, 3 months, and 6 months) on PD mice. EGCG also ameliorated PFF-induced degeneration of TH immuno-positive neurons and accumulation of p-α-syn in the SN and striatum at 6 months. Additionally, EGCG reduced the expression of pro-inflammatory cytokines while promoting the release of anti-inflammatory cytokines. EGCG exerts a neuroprotective effect on long-term progression of the PD model.

Widely targeted metabolic profiling provides insights into variations in bioactive compounds and antioxidant activity of sesame, soybean, peanut, and perilla.

Oilseeds are important sources of diversified nutraceuticals with marked health attributes. Thus, a better understanding of metabolome differences between common oilseeds will be conducive to the food pharmacy. This study aimed to compare the metabolite profiles and antioxidant activity of sesame, soybean, peanut, and perilla seeds and reveal the variation in bioactive compounds. LC-MS-based widely targeted metabolic profiling identified a total of 975 metabolites, of which 753 were common to the four crops. Multivariate analyses unveiled a crop-specific accumulation of metabolites, with 298-388 DAMs (differentially accumulated metabolites) identified. Amino acid metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and lipid metabolism were the most differentially regulated pathways. Furthermore, we revealed the variation in the relative content of 48, 20, 18, 9, 18, 11, and 6 differentially accumulated bioactive flavonoids, phenolic acids, amino acids, vitamins, terpenoids, alkaloids, and coumarins, respectively. Most of the flavonoids accumulated highly in soybean, followed by perilla. Sesame exhibited a better amino acid profile than other oilseeds. DPPH and FRAP assays showed that the antioxidant activity of perilla seed extracts was the highest, followed by soybean, peanut, and sesame. Our results provide data support for the comprehensive use of sesame, perilla, soybean, and peanut seeds in food, and pharmaceutical industries.

Cytological DNA methylation for cervical cancer screening: a validation set.

Background: In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants. Methods: From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results. Results: Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]). Conclusions: The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.

Inhibition of AGEs-RAGE-PP2A Axis Alleviates Cognitive Impairment after Chronic Heart Failure.

To investigate the effect of the AGEs-RAGE-PP2A axis on cognitive impairment (CI) after chronic heart failure (CHF). Mice were divided into six groups: Sham, TAC, Sham+RAGE-/-, TAC+RAGE-/-, AG, and FTY720 group. AG mice and FTY720 mice were treated with AGEs inhibitor (aminoguanidine, AG) and PP2A activator (FTY720) respectively after TAC surgery. The cardiac function of AG and TAC+RAGE-/- mice was significantly better than that of TAC mice (P<0.05). However, the heart function of FTY720 mice were just improved a part of that. To behavioral function, the escape latency period of the TAC+RAGE-/-, AG and FTY720 mice were significantly shorter (P<0.05), and the times of platform crossings and residence time of them were significantly improved (P<0.05). HE staining and silver staining show the structure of TAC+RAGE-/-, AG and FTY720 mice were more complete. Also, in these three groups, the expression of Aß and p-tau protein in the brain can be significantly down-regulated (P<0.05) and the PP2A protein expression level was up-regulated (P<0.05). And the expression of hippocampal Bax, Cyt-C, and Caspase-3 of that were all down-regulated (P<0.05), and Bcl-2 was up-regulated (P<0.05). Deficient of AGEs, RAGE and activating PP2A can significantly attenuate the cognitive impairment in CHF mice, and protect the brain structure. This mechanism seems via reducing the expression of Aß, p-tau, and apoptotic protein.

Integrating transcriptome and phytohormones analysis provided insights into plant height development in sesame.

Plant height is a key agronomic trait influencing crops yield. The height of sesame plants is important for yield performance, lodging resistance and plant architecture. Although plant height is significantly distinct among sesame varieties, the genetic basis of plant height remains largely unknown. In this study, in order to tackle genetic insights into the sesame plant height development, a comprehensive transcriptome analysis was conducted using the stem tips from two sesame varieties with distinct plant height, Zhongzhi13 and ZZM2748, at five time points by BGI MGIseq2000 sequencing platform. A total of 16,952 genes were differentially expressed between Zhongzhi13 and ZZM2748 at five time points. KEGG and MapMan enrichment analyses and quantitative analysis of phytohormones indicated that hormones biosynthesis and signaling pathways were associated with sesame plant height development. Plenty of candidate genes involved in biosynthesis and signaling of brassinosteroid (BR), cytokinin (CK) and gibberellin (GA) which were major differential hormones between two varieties were identified, suggesting their critical roles in plant height regulation. WGCNA revealed a module which was significantly positively associated with the plant height trait and founded SiSCL9 was the hub gene involved in plant height development in our network. Further overexpression in transgenic Arabidopsis validated the function of SiSCL9 in the increase of plant height by 26.86%. Collectively, these results increase our understanding of the regulatory network controlling the development of plant height and provide a valuable genetic resource for improvement of plant architecture in sesame.

The pattern of alternative splicing and DNA methylation alteration and their interaction in linseed (Linum usitatissimum L.) response to repeated drought stresses.

BACKGROUND: Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. RESULTS: We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. CONCLUSION: Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.

Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.

Introduction: Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo. Methods: We established a PD model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL6 mice (25 mg/kg/d, 5 d, i.p.) to investigate the neuropharmacological modulation of Nic pretreatment (2.5 mg/kg/d, 5 d, i.p., 30 min before MPTP injection) from the perspectives of neurobehavioral assessment, the pathological alterations, microglial cell inflammation and MAPK signaling pathways in specific brain regions. Results: The open field test, elevated plus maze, rotarod and traction test suggested that Nic pretreatment could significantly improve MPTP-induced motor impairment and had an anxiolytic effect. Nic was found to improve neuroapoptosis, enhance tyrosine hydroxylase activity, and reduce the accumulation of the phosphorylated α-synuclein in the substantia nigra and striatal regions of PD mice by TUNEL and immunohistochemical assays. Immuno-fluorescent method for labeling Iba1 and CD68 indicated that Nic remarkably alleviates the activation of microglia which represents the M1 polarization state in the mice brain under MPTP stimulation. No significant difference in the expression of p38/MAPK pathway was found in the nigrostriatal regions, while Nic could significantly inhibit the elevated p-JNK/JNK ratio and increase the declined p-ERK/ERK ratio in the substantia nigra of MPTP-exposed brains, which was further confirmed by the pretreatment of CYP2A5 inhibitor to decline the metabolic activity of Nic. Discussion: The molecular signaling mechanism by which Nic exerts its neuroprotective effects against PD may be achieved by regulating the JNK and ERK signaling pathways in the nigra-striatum related brain regions.

Current Progress, Applications and Challenges of Multi-Omics Approaches in Sesame Genetic Improvement.

Sesame is one of the important traditional oil crops in the world, and has high economic and nutritional value. Recently, due to the novel high throughput sequencing techniques and bioinformatical methods, the study of the genomics, methylomics, transcriptomics, proteomics and metabonomics of sesame has developed rapidly. Thus far, the genomes of five sesame accessions have been released, including white and black seed sesame. The genome studies reveal the function and structure of the sesame genome, and facilitate the exploitation of molecular markers, the construction of genetic maps and the study of pan-genomes. Methylomics focus on the study of the molecular level changes under different environmental conditions. Transcriptomics provide a powerful tool to study abiotic/biotic stress, organ development, and noncoding RNAs, and proteomics and metabonomics also provide some support in studying abiotic stress and important traits. In addition, the opportunities and challenges of multi-omics in sesame genetics breeding were also described. This review summarizes the current research status of sesame from the perspectives of multi-omics and hopes to provide help for further in-depth research on sesame.

Resequencing of 410 Sesame Accessions Identifies SINST1 as the Major Underlying Gene for Lignans Variation.

Sesame is a promising oilseed crop that produces specific lignans of clinical importance. Hence, a molecular description of the regulatory mechanisms of lignan biosynthesis is essential for crop improvement. Here, we resequence 410 sesame accessions and identify 5.38 and 1.16 million SNPs (single nucleotide polymorphisms) and InDels, respectively. Population genomic analyses reveal that sesame has evolved a geographic pattern categorized into northern (NC), middle (MC), and southern (SC) groups, with potential origin in the southern region and subsequent introduction to the other regions. Selective sweeps analysis uncovers 120 and 75 significant selected genomic regions in MC and NC groups, respectively. By screening these genomic regions, we unveiled 184 common genes positively selected in these subpopulations for exploitation in sesame improvement. Genome-wide association study identifies 17 and 72 SNP loci for sesamin and sesamolin variation, respectively, and 11 candidate causative genes. The major pleiotropic SNPC/A locus for lignans variation is located in the exon of the gene SiNST1. Further analyses revealed that this locus was positively selected in higher lignan content sesame accessions, and the "C" allele is favorable for a higher accumulation of lignans. Overexpression of SiNST1C in sesame hairy roots significantly up-regulated the expression of SiMYB58, SiMYB209, SiMYB134, SiMYB276, and most of the monolignol biosynthetic genes. Consequently, the lignans content was significantly increased, and the lignin content was slightly increased. Our findings provide insights into lignans and lignin regulation in sesame and will facilitate molecular breeding of elite varieties and marker-traits association studies.

Nuanxinkang prevents the development of myocardial infarction-induced chronic heart failure by promoting PINK1/Parkin-mediated mitophagy.

BACKGROUND: Mitochondrial dysfunction is an important pathological feature of chronic heart failure (CHF). Regulation of mitophagy can effectively maintain mitochondrial homeostasis and energy metabolism, thereby inhibiting the development of CHF. Nuanxinkang (NXK), a Chinese herbal compound preparation, has significant cardioprotective effects on CHF; however, its underlying mechanism on mitophagy has not been completely clarified. This research intended to investigate the mechanism of NXK in treating myocardial infarction (MI)-induced CHF. METHODS: The left anterior descending coronary artery (LAD) ligation surgery was performed to establish an MI-induced CHF model in male C57BL/6 mice. From 1 day after surgery, mice were given NXK (0.41, 0.82 or 1.65 g/kg/d), Perindopril (PDPL, 0.607 mg/kg/d), or an equivalent amount of sterile water by gavage for 28 continuous days. Then, mice were examined for cardiac function, myocardial fibrosis, cardiomyocyte apoptosis, mitochondrial structure and mitophagy levels of cardiomyocytes, etc. In addition, a hypoxic injury model was created using HL-1 cardiomyocytes from wild-type (WT) mice. HL-1 cells were pretreated with or without NXK-containing serum. Mitochondrial function and mitophagy levels were examined in HL-1 cells. RESULTS: In MI-induced CHF mice, cardiac dysfunction, severe cardiac remodeling, elevated levels of oxidative stress, reduced ATP levels, and inhibition of PINK1/Parkin-mediated mitophagy were observed. High-dose NXK treatment (1.65 g/kg/d) significantly improved myocardial energy metabolism, inhibited cardiac remodeling, improved cardiac function, and restored cardiac PINK1/Parkin-mediated mitophagy levels to some extent in MI mice. In vitro, elevated levels of mitochondrial reactive oxygen species (ROS) with impaired mitochondrial membrane potential (ΔΨm) were observed in hypoxic HL-1 cells. While NXK treatment significantly protected cardiomyocytes from hypoxia-induced mitochondrial dysfunction, which is consistent with the in vivo results. Further studies showed that NXK could increase PINK1/Parkin-mediated mitophagy levels in cardiomyocytes, which could be blocked by the mitophagy inhibitor Mdivi-1. CONCLUSION: In conclusion, NXK could prevent cardiac mitochondrial dysfunction and improve cardiac function against MI-induced CHF by promoting Pink1/Parkin-mediated mitophagy, which represents a very prospective strategy for the treatment of CHF.

Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

The pattern of alternative splicing and DNA methylation alteration and their interaction in linseed (Linum usitatissimum L) response to repeated drought stresses

BACKGROUND: Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. RESULTS: We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. CONCLUSION: Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.

Comparative Metabolomics Analysis of Different Perilla Varieties Provides Insights into Variation in Seed Metabolite Profiles and Antioxidant Activities.

Perilla seeds are essential functional foods and key ingredients in traditional medicine. Herein, we investigated the variation in phytochemical profiles and antioxidant activities of twelve different perilla seeds. The seeds showed significant variations in total phenolic and flavonoid contents ranging from 16.92 to 37.23 mg GAE/g (GAE, gallic acid equivalent) and 11.6 to 19.52 mg CAE/g (CAE, catechin equivalent), respectively. LC-QqQ-MS (liquid chromatography triple quadrupole tandem mass spectrometry)-based widely targeted metabolic profiling identified a total of 975 metabolites, including 68-269 differentially accumulated metabolites (DAMs). Multivariate analyses categorized the seeds into four groups based on the seed coat and leaf colors. Most key bioactive DAMs, including flavonoids (quercetin-3'-O-glucoside, prunin, naringenin, naringenin chalcone, butin, genistin, kaempferol-3-O-rutinoside, etc.), amino acids (valine, lysine, histidine, glutamine, threonine, etc.), and vitamins (B1, B3, B6, U, etc.) exhibited the highest relative content in PL3 (brown seed, purple leaf), PL1 (white seed, green-purple leaf), and PL4 (white seed, green leaf) groups, respectively. Meanwhile, key differentially accumulated phenolic acids showed a higher relative content in PL1 and PL4 than in other groups. Both seeds exhibited high antioxidant activities, although those of PL2 (brown seed, green leaf) group seeds were the lowest. Our results may facilitate the comprehensive use of perilla seeds in food and pharmaceutical industries.

Signal Source Localization with Long-Term Observations in Distributed Angle-Only Sensors.

Angle-only sensors cannot provide range information of targets and in order to determine accurate position of a signal source, one can connect distributed passive sensors with communication links and implement a fusion algorithm to estimate target position. To measure moving targets with sensors on moving platforms, most of existing algorithms resort to the filtering method. In this paper, we present two fusion algorithms to estimate both the position and velocity of moving target with distributed angle-only sensors in motion. The first algorithm is termed as the gross least square (LS) algorithm, which takes all observations from distributed sensors together to form an estimate of the position and velocity and thus needs a huge communication cost and a huge computation cost. The second algorithm is termed as the linear LS algorithm, which approximates locations of sensors, locations of targets, and angle-only measures for each sensor by linear models and thus does not need each local sensors to transmit raw data of angle-only observations, resulting in a lower communication cost between sensors and then a lower computation cost at the fusion center. Based on the second algorithm, a truncated LS algorithm, which estimates the target velocity through an average operation, is also presented. Numerical results indicate that the gross LS algorithm, without linear approximation operation, often benefits from more observations, whereas the linear LS algorithm and the truncated LS algorithm, both bear lower communication and computation costs, may endure performance loss if the observations are collected in a long period such that the linear approximation model becomes mismatch.

Discovering favorable genes, QTLs, and genotypes as a genetic resource for sesame (Sesamum indicum L.) improvement.

Sesame (Sesamum indicum L.) is an ancient diploid oilseed crop with high oil content, quality protein, and antioxidant characteristics that is produced in many countries worldwide. The genes, QTLs, and genetic resources of sesame are utilized by sesame researchers and growers. Researchers have identified the many useful traits of this crop, which are available on different platforms. The genes, genotypes, QTLs, and other genetic diversity data of sesame have been collected and stored in more than nine genomic resources, and five sesame crop marker databases are available online. However, data on phenotypic and genotypic variability, which would contribute to sesame improvements, are limited and not yet accessible. The present study comprehensively reviewed more than 110 original published research papers and scientifically incorporated the results. The candidate genes, genotypes, and QTLs of significantly important traits of sesame were identified. Genetic resources related to grain yield and yield component traits, oil content and quality, drought tolerance, salt tolerance, waterlogging resistance, disease resistance, mineral nutrient, capsule shattering resistance, and other agronomic important traits of sesame were studied. Numerous candidate genotypes, genes, QTLs, and alleles associated with those traits were summarized and discovered. The chromosome regions and linkage groups, maps associated with the best traits, and candidate genes were also included. The variability presented in this paper combined with sesame genetic information will help inform further sesame improvement.

Metabolome genome-wide association study provides biochemical and genetic insights into natural variation of primary metabolites in sesame.

Plants' primary metabolites are of great importance from the survival and nutritional perspectives. However, the genetic bases underlying the profiles of primary metabolites in oilseed crops remain largely unclear. As one of the main oilseed crops, sesame (Sesamum indicum L.) is a potential model plant for investigating oil metabolism in plants. Therefore, the objective of this study is to disclose the genetic variants associated with variation in the content of primary metabolites in sesame. We performed a comprehensive metabolomics analysis of primary metabolites in 412 diverse sesame accessions using gas chromatography-mass spectrometry and identified a total of 45 metabolites, including fatty acids, monoacylglycerols (MAGs), and amino acids. Genome-wide association study unveiled 433 significant single-nucleotide polymorphism loci associated with variation in primary metabolite contents in sesame. By integrating diverse genomic analyses, we identified 10 key candidate causative genes of variation in MAG, fatty acid, asparagine, and sucrose contents. Among them, SiDSEL was significantly associated with multiple traits. SiCAC3 and SiKASI were strongly associated with variation in oleic acid and linoleic acid contents. Overexpression of SiCAC3, SiKASI, SiLTPI.25, and SiLTPI.26 in transgenic Arabidopsis and Saccharomyces cerevisiae revealed that SiCAC3 is a potential target gene for improvement of unsaturated fatty acid levels in crops. Furthermore, we found that it may be possible to breed several quality traits in sesame simultaneously. Our results provide valuable genetic resources for improving sesame seed quality and our understanding of oilseed crops' primary metabolism.

The fluorescent aptasensor based on CRISPR-Cas12a combined with TdT for highly sensitive detection of cocaine.

Ultrasensitive and specific detection of cocaine is of great significance for monitoring cocaine abuse. Herein, a fluorescent aptasensor via coupling CRISPR-Cas12a, with magnetic nanoparticles (MNPs), split-aptamer, and terminal deoxynucleotidyl transferase (TdT), was developed for the detection of cocaine. In short, the complete cocaine aptamer is split into two parts, one is modified on magnetic nanoparticles (MNPs) and the other is free. The presence of cocaine will mediate the binding of these two segments. Then TdT will mediate the extension to form an ultra-long sequence that can bind with multiple CRISPR-Cas12a resulting in the trans-cleavage activity of CRISPR-Cas12a being triggered. Thence, the DNA reporter which is bi-labeled with fluorophore and quencher is cleaved resulting in the generation of a fluorescence signal. The developed fluorescent aptasensor realizes the detection of cocaine with excellent sensitivity and specificity. The detection limit is low down to 33 pM, and the linear range is from 330 to 1.65 × 105 pM. Most importantly, this fluorescent aptasensor can be successfully applied to the determination of cocaine in human plasma samples.

Genome-wide association analysis and transcriptome reveal novel loci and a candidate regulatory gene of fatty acid biosynthesis in sesame (Sesamum indicum L.).

The regulatory mechanisms of fatty acid (FA) biosynthesis and triacylglycerols (TAGs) assembly remain largely misunderstood in sesame. Gas chromatography was used to analyze the natural variation in FA compositions and oil content (OC) in 400 sesame accessions grown in three different environments. The phenotypic data was associated with the newly released SNP data from whole-genome resequencing, and 43 significant loci for FA and OC were identified. Comparative transcriptomics analysis of high-OC and low-OC materials was performed, and 515 differentially expressed genes (DEGs) were identified across three seed developmental stages. By integrating the genome-wide association study (GWAS) and DEGs analysis, twenty candidate genes were identified, of which SiTPS1 (trehalose-6-phosphate synthase 1) has emerged as a key regulatory gene of FAs and TAGs metabolism in sesame. Overexpression of SiTPS1 in transgenic Arabidopsis influenced FA composition and significantly increased OC. Our study provides resources for the markers-based improvement of OC and quality in sesame and other crops.