OSW-1, a steroidal disaccharide isolated from the bulbs of Ornithogalum saundersiae, has been extensively studied for its extremely potent cytotoxicity against the National Cancer Institute's 60 cancer cell lines with an average IC50 of 0.78 nM, while exhibiting selectivity toward normal cells. Although OSBP and ORP4L have been identified as its binding targets, their known functions appear insufficient to account for the compound's exceptional potency, suggesting the involvement of additional mechanisms and targets. Therefore, elucidating novel target proteins associated with its activity is essential for the further development of this molecule. Here, we disclose that OSW-1 can block the glycolytic pathway and trigger compensatory mitochondrial oxidative phosphorylation. This previously uncharacterized mechanism is relevant to the key rate-limiting enzyme, enolase 1 (ENO1), which shows subnanomolar affinity with OSW-1. Our study repurposes OSW-1 to be a small-molecule probe to investigate the function of ENO1 and a promising candidate for metabolism-targeted anticancer therapy.

Loquat (Eriobotrya japonica) regeneration and transformation are difficult, hindering gene function studies. To overcome this limitation, we developed a rapid and stable regeneration and transformation system for hairy roots in loquat by optimising key conditions, in order to explore the potential functions of key genes involved in root growth and development. LEAFY COTYLEDON 2 (LEC2) is a central hub linking embryonic development, lipid synthesis, root system development, and hormonal regulation. However, the role of the LEC2 protein in regulating root growth and development in loquat remains unclear. This study demonstrates a specific interaction between LEC2 and FUSCA3 (FUS3) in loquat, with FUS3 acting downstream of LEC2. Overexpression of LEC2 or FUS3 showed longer root length and increased root numbers, while loss-of-function mutants of either LEC2 or FUS3 exhibited shorter root lengths and reduced root numbers, and overexpression of FUS3 effectively compensated for the root growth defects in LEC2 knockout mutants. In summary, the stable Agrobacterium rhizogenes-mediated transformation system provides an effective approach for gene function analysis and genetic engineering research in loquat, and the LEC2-FUS3 complex functions as a key regulator in auxin-regulated root growth and development.

Loquat fruit is highly susceptible to postharvest browning, which significantly reduces its commercial value. The molecular mechanisms underlying this disorder are not fully elucidated. Physiological analysis revealed that the white-fleshed cultivar 'HB' is particularly susceptible to browning, a process associated with phenylpropanoid metabolism (e.g., lignin content), reactive oxygen species balance (H2O2 accumulation and DPPH radical scavenging capacity), phenolic metabolism, and membrane lipid peroxidation. Integrated transcriptomic and metabolomic analyses identified a key transcription factor, EjWRKY22, whose expression was strongly correlated with the accumulation of sinapyl alcohol, a major lignin precursor. Functional experiments confirmed that EjWRKY22 enhances H2O2 production and promotes lignin deposition, thereby accelerating browning. Further molecular analysis (Y1H, Dual-LUC, EMSA) demonstrated that EjWRKY22 directly activates the transcription of its downstream target gene Ej4CL5, leading to the upregulation of 4-coumarate: CoA ligase (4CL), a rate-limiting enzyme in lignin biosynthesis. This results in increased lignin deposition, acts synergistically with H2O2 accumulation, and ultimately drives fruit browning. Functional validation confirmed that Ej4CL5 positively regulates browning through lignin synthesis. This study is the first to identify a novel EjWRKY22-Ej4CL5 transcriptional regulatory module, systematically elucidating the molecular pathway of postharvest browning in loquat fruit. It provides candidate genes and a theoretical basis for preventing postharvest browning in loquat fruit.

IntroductionThe wheat blast fungus Magnaporthe oryzae pathotype Triticum (MoT) poses a severe threat to global wheat (Triticum aestivum L.) production, yet the molecular mechanisms underlying tissue invasion remain poorly understood.MethodsWe performed dual RNA-seq analysis of MoT-inoculated wheat leaves at 0, 24, 36, and 48 hpi, mapping reads separately to the wheat and M. oryzae genomes to capture stage-specific host responses and pathogen gene expression across progressive infection stages.ResultsWheat exhibited pronounced stage-specific transcriptional reprogramming, with peak differential gene expression at 36 hpi and visible symptoms at 48 hpi. The 24 hpi stage was characterized by rapid induction of immune- and defense-related pathways, including innate immunity and detoxification processes, along with downregulation of cell wall and membrane biosynthesis. By 36 hpi, wheat maintained sustained activation of immune and detoxification pathways, while chloroplast- and photosynthesis-associated genes were broadly repressed, consistent with transcriptional features of metabolic constraint. At 48 hpi, coinciding with lesion initiation, transcriptomes showed persistent, metabolically costly immune and defense responses together with extensive suppression of photosynthesis- and chloroplast-associated functions, which were associated with metabolic strain and a transition toward necrosis. Analysis of pathogen-derived reads revealed temporal induction of multiple effector candidates, including known M. oryzae orthologs and additional effector-like proteins, highlighting coordinated temporal patterns between host immune and metabolic response as well as stage-specific pathogen effector expression.DiscussionTogether, these findings provide a temporal framework for wheat blast susceptibility and highlight key host pathways and effector candidates that define critical windows for functional dissection of MoT virulence and wheat susceptibility.

The blast fungus Magnaporthe oryzae infects plants using an appressorium that generates force to breach the leaf cuticle. Appressorium development follows a cell-cycle-regulated morphogenetic program requiring autophagy-associated death of the spore. How proliferative growth is coordinated with cell death remains unclear. Here, we show that each conidial cell follows a distinct developmental program essential for infection. Using quantitative live-cell imaging, we tracked 10 organelle types during appressorium morphogenesis in wild-type and Δatg8 mutant strains. Photoactivatable GFP microscopy revealed that mitochondria traffic from a single conidial cell into the appressorium, while the remaining cells undergo autophagy. Organelle inheritance occurs independently of cell-cycle checkpoints but coincides with spore germination. Photoconvertible fluorescence microscopy defined the temporal sequence of organelle movement and de novo biogenesis. Our findings reveal that coordinated spatiotemporal control of autophagy and organelle trafficking is necessary for rice blast infection.

Loquat (Eriobotrya japonica Lindl.), a subtropical evergreen species of the Rosaceae family, faces industry constraints in industrial development due to its sensitivity to freezing temperatures and low photosynthetic efficiency. Polyploid loquats, particularly triploids, exhibit enhanced stress resistance, vigorous growth, and seedless fruit production. In this study, triploid F1 progeny (B431 × GZ23) was obtained through hybridization between diploid (GZ23) and tetraploid (B431) parents. Under -3°C stress, the triploid lines exhibited significantly improved freezing tolerance and photosynthetic performance, as evidenced by chlorophyll fluorescence parameters and ultrastructural integrity. Lipidomics profiling across all B431 × GZ23 lines revealed that phosphatidylcholine (PC), particularly the abundant unsaturated PC species 18:2/18:2, played a key role in these adaptive advantages. Compared to the parental lines, EjFAD2 expression was specifically upregulated in triploid loquats under freezing stress. Consistent lipidomic and gene expression patterns across three B431 × GZ23 lines ruled out line-specific mutations. Heterologous expression of EjFAD2 in Arabidopsis increased freezing tolerance. Co-expression analysis identified EjMYBS3 as a regulator that binds to the EjFAD2 promoter, and its overexpression in transgenic Arabidopsis enhanced freezing tolerance. Transient expression of EjFAD2 and EjMYBS3 increased the content of PC 18:2/18:2 in loquat, which contributed to the maintenance of photosystem activity under freezing stress, thereby enhancing the freezing tolerance of loquat. Collectively, these findings provide preliminary insights into the molecular mechanisms underlying cold resistance in polyploid loquats and highlight the regulatory role of EjFAD2 and EjMYBS3 in freezing stress response.

Loquat (Eriobotrya japonica Lindl.) is one of the most important subtropical evergreen fruit trees. However, due to the lack of widely applicable genetic transformation platforms, the research about gene functional characterization and molecular mechanisms is largely confined. In this study, the efficient protocol of protoplast isolation (the enzyme solution composed of 2.4% macerozyme R-10, 4.8% cellulase RS, dissolved in a 0.6 M mannitol solution) and the method of protoplast purification (CPW solution containing 5% sucrose and 11% mannitol) have been achieved with protoplast yields of 12.6 × 106/g·FW, reaching a viability rate of up to 91%. A protoplast transient gene expression system has been established with an efficiency of approximately 40% using GFP reporter gene. Using this reliable and efficient system, the protein localization characteristics of transcription factor EjDELLA, EjbHLH79, and marker gene OsPHT4 were also utilized for further analysis. To our knowledge, this is the first report on establishing an efficient system for protoplast isolation, purification, and transformation of loquat mesophyll. The system reported here will definitely promote rapid progress in breeding, genetic transformation, and molecular research.

The blast fungus Magnaporthe oryzae infects plants using a specialised infection structure called an appressorium that generates physical force to break the rice leaf cuticle. Appressorium development follows a cell cycle-controlled morphogenetic program, requiring autophagy-associated cell death of the fungal spore from which the infection cell develops. How proliferative growth of the fungus is regulated at the same time as programmed cell death, however, is unknown. In this study, we provide evidence that each cell of the conidium undergoes a separate developmental program, which is necessary for plant infection. Using quantitative live-cell imaging, we monitored trafficking of ten organelle types during appressorium morphogenesis in a wild-type M. oryzae strain and isogenic Δ atg8 autophagic mutant. High-resolution microscopy using a photoactivatable green fluorescent protein revealed that organelle trafficking occurs from a single conidium cell into the appressorium, while the remaining two cells undergo autophagy. Organelle inheritance operates independently of cell cycle checkpoints but is always associated with spore germination. We furthermore defined the temporal sequence of organelle movement and de novo organelle biogenesis in the incipient appressorium using photoconvertible fluorescent localisation microscopy. Taken together, our study reveals how synchronous spatiotemporal control of autophagy and organelle trafficking is necessary for rice blast infection. ### Competing Interest Statement The authors have declared no competing interest. Biotechnology and Biological Sciences Research Council, BS/E/J/000PR9797, BB/V016342/1 National Science Foundation CAREER award, IOS-2141858 Halpin Scholarship in Rice Blast Research Gatsby Charitable Foundation

Approximately 6.6 million km2 of China’s territory consists of drylands at high desertification risk. Despite ecological vulnerability, these regions remain understudied in biodiversity research. DNA barcoding provides an efficient tool for rapid species identification, offering significant potential for biodiversity conservation and ecological surveys in drylands. However, comprehensive reference data for China’s drylands are currently lacking, underscoring the urgent need for a reliable, extensive, and traceable DNA barcode reference library. To address this gap, we systematically surveyed plant diversity across nearly all Chinese drylands from 2013 to 2021. Our study documented 1,140 species, representing 434 genera, 76 families, and 29 orders. Based on this effort, we constructed the most comprehensive DNA barcode reference library for native dryland seed plants in China, comprising 13,246 sequences across five markers: rbcL (3,056), matK (3,332), ITS (3,358), psbA-trnH (1,770), and trnL-F (1,730). This resource establishes a critical foundation for integrated taxonomic research, biodiversity monitoring, and environmental impact assessments. Moreover, it supports initiatives in desertification control, plant conservation, and sustainable development in China’s dryland regions.

Taste is an important fruit quality trait in commercial fruits and is influenced by transcriptional regulation. NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play crucial roles in fruit ripening. However, the regulatory mechanism of NAC TF on taste formation in loquat fruit remains unclear. Here, we identified a NAC TF, EjNAC25, which is highly expressed in mature loquat fruits and closely related to sugar and malic acid content. After isolation of EjNAC25 from early-maturing seedless triploid loquat, transient transformation in loquat and stable overexpression in tomato were performed. The result showed that EjNAC25 positively regulated the accumulation of sugar and malic acid. Dual-luciferase assays and yeast one-hybrid experiments showed that EjNAC25 could directly bind to the promoter regions of the neutral invertase gene EjNI and the tonoplast dicarboxylate transporter EjtDT2, thereby activating their transcription. Furthermore, overexpression of EjNI increased the activity of neutral invertase, which enhanced the conversion of sucrose to fructose and glucose. Overexpression of EjtDT2 promoted the accumulation of malic acid. In summary, our study revealed that EjNAC25 positively regulates sugar and malic acid content by activating EjNI and EjtDT2 in loquat. This study provides a theoretical basis for regulatory mechanisms of NAC TF on fruit taste and contributes to the future improvement of loquat fruit quality through biotechnology.

Coniferous species are not only important timber sources but also have significant ecological value. Somatic embryogenesis is a powerful tool for large-scale propagation of conifers. Partial desiccation treatment (PDT) significantly promotes the germination rate of somatic embryos (SEs). However, the molecular mechanism behind this is far from understanding. In this study, morphological analysis of the Picea asperata SEs showed a significant remodeling of the cell wall structure in the hypocotyl region following PDT. Transcriptome and metabolome analysis were performed to identify the key regulator of cell wall modification in response to PDT. The results showed that the metabolic products of cellular components, such as sucrose, fructose, and glucose, were the main metabolites accumulated in the SEs after PDT. Transcriptional regulatory network analysis predicted PaMYB12 as a potential hub gene. Yeast-one-hybrid and bimolecular fluorescence complementation assay showed that PaMYB12 could directly bind to the promoter regions of genes associated with cell wall component metabolism and cell wall remodeling, including GOLS (MA_3384g0010), EXPA (MA_10425823g0010), XTH (MA_10429607g0010), and BGLU (MA_48585g0010). Furthermore, the transcript levels of these genes were increased/decreased by transient overexpression/repression of PaMYB12. In summary, PDT promotes cell wall remodeling to facility SE germination. PaMYB12, which was shown to regulate the expression of multiple genes involved in cell wall component metabolism and remodeling, is proposed to be the key regulator of this process. This knowledge would contribute to a deeper understanding of somatic embryo germination and potentially inform strategies for improving plant regeneration techniques.

With climate change and human activities, the Qinghai-Xizang Plateau (QXP) faces increasing risk of desertification. High-altitude desert plants exhibit remarkable resilience, making them ideal for restoring desertified lands on the QXP. Sandrice, a medicinal herb, disperses widely across Asian deserts including the QXP. To elucidate the molecular mechanism of sandrice adaptation to the QXP, in situ metabolome and transcriptome analyses were conducted between high and mid-altitude ecotypes. Comparison analysis revealed that up-regulated genes in the high-altitude ecotype were primarily involved in phenylpropanoid and flavonoid biosynthesis pathways, leading to higher accumulation of these medicinal metabolites in the high-altitude ecotype. Additionally, Ka/Ks analysis indicated significant divergence in DEGs such as FLS, CCoAOMT and HCT between the two ecotypes. Population genetic analysis across altitude gradients showed that FST values for genes in phenylpropanoid and flavonoid biosynthesis pathways were higher than genome-wide FST values. Notably, nine out of 15 genes in these pathways, including FLS and HCT, were fixed in all the high-altitude populations, as a consequence of strong directional selection by the alpine desert environment, which supports phenylpropanoids and flavonoids play critical roles for sandrice adapting to alpine desert environments. Moreover, balancing selection could also facilitate sandrice's spread across diverse desert conditions, whose signal was witnessed in CCoAOMT within the QXP populations. This study bridges our understanding from medicinal metabolites to the genetic basis of alpine ecotypes adapted to harsh environments on the QXP, providing valuable molecular insights and genetic resources for ecosystem restoration and the indigenous nature of high-altitude medicinal plants.

Loquat (Eriobotrya japonica) is an economically important evergreen fruit tree. Its leaves serve as the primary site of photosynthesis, provide nutrients for fruit development, and are utilized in studies on stress resistance, disease resistance, and medicine. To better define the stages of leaf development in loquat, this study first established characteristic morphological indicators for each developmental phase and generated a high-precision transcriptome dataset. Transcriptomic analysis revealed that the gene Eja14G002720 is involved in leaf development and is light-responsive. It encodes a CAAX-box protein that is a homolog of Arabidopsis thaliana AtBCM1, hence its designation as EjBCM1-like. Functional characterization demonstrated that EjBCM1-like plays a critical role in chlorophyll (Chl) accumulation during loquat leaf development. An electrophoretic mobility shift assay (EMSA) confirmed that EjBCM1-like is a novel target gene of EjHY5. Further dual-luciferase and yeast one-hybrid (Y1H) assays indicated that EjHY5 and EjGLK1 bind to the promoter of EjBCM1-like and regulate its expression. This study provides valuable and precise transcriptomic resources for investigating leaf development in loquat and enhances our understanding of the regulatory network underlying Chl metabolism.

Malic acid is the major organic acid in loquat fruit, contributing to the sourness of fruit and affecting fruit flavor. However, the transcriptional regulation of malic acid in loquat is not well understood. Here, we discovered a MADS-box transcription factor (TF), EjAGL18, that regulated malic acid accumulation in loquat. EjAGL18 is a nucleus-localized TF without transcriptional activity. The expression of EjAGL18 increased during fruit ripening, opposite to the accumulation pattern of malic acid in loquat. The transient overexpression of EjAGL18 in loquat fruit downregulated malic acid accumulation and the transcriptional level of the tonoplast dicarboxylate transporter EjtDT1. Conversely, silencing EjAGL18 in loquat fruit upregulated the malic acid content and EjtDT1 expression level. Dual-luciferase assays and yeast one-hybrid experiments further confirmed that EjAGL18 could bind to the promoter of EjtDT1 and repress its transcriptions. Furthermore, the transient overexpression of EjtDT1 in loquat fruit increased the malic acid content. These results revealed that EjAGL18 negatively regulates malic acid content by repressing EjtDT1 in loquat. This study broadens the understanding of the MADS-box TF’s regulatory mechanisms in malic acid and provides new insights into fruit flavor improvement in loquat.

Among 18 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologous genes existing in the banana genome there is a gene, MaACO2, that participates in banana fruit ripening. We constructed a banana nuclear yeast library and identified the transcriptional and post-translational proteins interacting with MaACO2 by OneHybrid and Two-Hybrid techniques. Twenty-eight proteins interacting with MaACO2 were screened by yeast Two-Hybrid. The interactions of chitinase 1 and glucan endo-1,3-beta-glucosidase with MaACO2 were verified by point-to-point reverse validation. Additionally, the 40 proteins were identified by yeast One-Hybrid, and the interactions of NAC21/22 and RING-H2 zinc finger protein ATL2 with MaACO2 promoter were also confirmed by reverse validation. The expression levels of glucan endo-1,3-beta-glucosidase, ATL2 and NAC21/22, were significantly increased at the 3rd stage of fruit maturity when the peel color was greener but not yellow. However, the expression of chitinase 1 was significantly increased at the 4th stage of fruit maturity and the pericarp color was more yellow but not green, and then the gene expression gradually decreased. Ethylene and 1-MCP promote and inhibit the expression of MaACO2 interacting protein coding genes, respectively.

Agriophyllum squarrosum(L.)Moq.,commonly known as sandrice,is an annual medicinal plant prevalent in the dunes across China's deserts.A garden trial revealed that flavonoid content varies among sandrice ecotypes due to long-term local adaptation to water variability.To investigate how sandrice responds to drought stress through the molecular metabolic regulation of flavonoids,we employed transcriptomic and metabolomic analyses during a 9-d ambient drought stress,examining three ecotypes along a precipitation gradient.The three ecotypes located in Dengkou(DK)County,Dulan(DL)County,and Aerxiang(AEX)village of northern China,which had 137,263,and 485 mm precipitation,respectively.Soil moisture content was 4.04%after drought stress,causing seedlings of the three sandrice ecotypes to display collapsed structures,yellowing leaves,wilting,and curling.Among these,DL exhibited superior drought tolerance,in which plant height increase(PHI)and leaf area(LA)were significantly higher than those of DK and AEX.Flavonoid-targeted metabolomics identified that rutin,isoquercitrin,and astragalin constituted over 95.00%of the 15 flavonoid metabolites detected.A total of 12 differentially accumulated flavonoids(DAFs)were found,with rutin being the most abundant(1231.57-2859.34 ng/100 mg fresh weight(FW)),showing a gradual increase along the precipitation gradient.Transcriptomic analysis revealed 14 common differentially expressed genes(DEGs)associated with flavonoid synthesis among the three ecotypes.Integrative analysis of DEGs and DAFs indicated that sandrice adapts to drought stress by activating different flavonoid synthesis pathways.In DK,the dihydrokaempferol-dihydroquercetin pathway,regulated by flavonoid 3'-monooxygenase(CYP75B1),likely enhances drought adaptation.In AEX,transcriptional repression by O-methylatransferase(OMT)shifts the metabolic flux from the quercetin-isorhamnetin pathway to the quercetin-isoquercetin-rutin pathway in response to drought.DL,the most drought-tolerant ecotype,appears to activate the naringenin-apigenin-luteolin route and employs a unique flavonoid accumulation pattern in response to drought stress.Our data reveal that flavonoid synthesis in sandrice is fine-tuned among ecotypes to cope with drought,offering valuable germplasm resources and evaluation methods for sandrice acclimation and providing insights into drought response in non-model plants.

Chilling injury is a great challenge in loquat fruit during cold storage. This study aims to better understand the mechanisms underlying the alleviation of chilling injury in loquat fruit. Here, we evaluated the effects of exogenous strigolactone (SL) treatment on the lignification and quality of loquat fruit during 4 degrees C storage. The results showed that 10 mu M SL treatment effectively delayed the increase in fruit firmness and the decline in soluble solids content. It maintained higher levels of fructose and glucose on day 35, and remained high levels of organic acids in the middle storage stages. SL-treated loquat fruit exhibited higher levels of total phenolics, total flavonoids, and soluble sugars in later storage phases. The 10 mu M SL treatment enhanced the activities of antioxidant enzymes and suppressed malondialdehyde accumulation, as well as inhibited lignin biosynthesis. Meanwhile, we confirmed one candidate gene, EjERF35, associated with lignin synthesis and accumulation in SL-treated fruits during cold storage. Transient overexpression of EjERF35 in tobacco leaves and loquat fruits, alongside stable genetic transformation in Arabidopsis, confirmed its functional roles in lignin accumulation. In summary, our results indicated that SL treatment maintains fruit quality by enhancing antioxidant capacity, preserving the fruit flavor, and delaying lignin accumulation in loquat fruit during cold storage. This study provides new insights into postharvest preservation and molecular regulation of lignification in loquat fruit.

Polyploidy plays a significant role in loquat breeding, particularly in triploid breeding for seedless fruit production. Currently, loquat polyploid breeding primarily relies on natural seedling selection and sexual hybridization approaches. In this study, unfertilized ovules from four loquat varieties were in vitro cultured. Gynogenesis and embryoid regeneration were achieved in ‘Xingning 1’ and ‘Huabai 1’, with ‘Xingning 1’ demonstrating the highest gynogenesis efficiency (21.63%). Flow cytometry and chromosome counting revealed that the obtained embryoid lines included haploid, diploid, tetraploid, hexaploid, and chimeric ploidy types. Further characterization of ‘Xingning 1’-derived embryoid lines through SSR markers and whole-genome resequencing confirmed that the haploid, diploid, tetraploid, and hexaploidy embryoid originated from haploid–somatic chimeras, diploid, doubled diploid and tripled diploid, respectively. Metabolic analysis showed a positive correlation between ploidy level and the content of both soluble sugars and organic acids. This study explored a novel platform for polyploid induction in loquat and may provide methodological insights for improvement of other perennial fruit trees.

Sand rice (Agriophyllum squarrosum), a pioneering annual plant thriving in deserts and sandy regions throughout the Asian interior, is believed to be a potential food and forage crop due to its significant nutritional and medicinal values. Previous metabolomics analyses have revealed that sand rice contains abundant flavonoid components, which are known for their wide applications in cosmetics, food, and pharmaceuticals. To optimize the use of flavonoids in sand rice, in this study, the response surface methodology (RSM) was selected to determine the optimal ultrasonic-assisted extraction (UAE) criteria for flavonoids extraction from the aerial part of sand rice firstly. Statistical analyses unveiled the optimum parameters for flavonoids extraction from sand rice could be 62% of ethanol concentration, 1:43 solid-toliquid ratio, 160 W for ultrasound power, and 52 degrees C for extraction temperature with extraction time of 12 min. Under this condition, the experiment optimum total flavonoid yield could reach at 15.24 mg/g, which was correspond to the maximum predicted value of RSM with 15.22 mg/g. Subsequently, the antifungal efficacy of these extracts was evaluated against three common plant pathogenic fungi, showing a significant inhibitory effect with the highest rate of inhibition reaching 25.3% at a concentration of 4 mg/mL, underscoring its potential as a natural antimicrobial agent. This study will not only provide a powerful method to extract flavonoids from a desert resource plant, but also pave the way for industrial development and application of the promising desert plants with high nutritional and medicinal values.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation. Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.