Enzymatic browning in fresh-cut products represents a significant quality deterioration issue impacting commercial value and consumer acceptance. This study investigated 3-mercapto-2-butanone, a naturally occurring thiol compound with established food safety approval, as a novel anti-browning agent. Concentration-response experiments demonstrated that 3-mercapto-2-butanone at 50 mu L/L achieved optimal browning inhibition in fresh-cut potato shreds, maintaining excellent color after 4 days while also preventing browning in tobacco leaf pulp, confirming broad cross-species efficacy. Transcriptomic analysis revealed biphasic molecular responses: immediate modulation of phenylalanine metabolism and phenylpropanoid biosynthesis pathways, followed by sustained antioxidant enhancement and metabolic reorganization. Direct enzymatic assays confirmed potent polyphenol oxidase (PPO) inhibition, with complete activity suppression at the optimal concentration. Mechanistic studies demonstrated practical preservation of phenolic substrates while preventing quinone intermediate accumulation during enzymatic reactions. Molecular modeling revealed competitive binding at the PPO active site, with thiol groups forming stable copper coordination complexes that displaced natural substrates and prevented enzymatic oxidation. These findings establish 3-mercapto-2-butanone as a multi-target browning inhibitor operating through direct enzyme inhibition, transcriptional modulation of protective pathways, and competitive substrate displacement. The compound's established safety profile as a food flavoring agent, combined with superior efficacy compared to conventional inhibitors, positions it as a promising commercial alternative for fresh-cut produce preservation.
Tobacco (Nicotiana tabacum) is both a major industrial crop and a foundational model organism for plant biology. While alternative splicing significantly diversifies transcriptome complexity, tobacco isoform annotation remains incomplete, hampered by the limitations of previous short-read sequencing efforts. To address this gap, we generated a long-read transcriptome dataset across five tobacco tissues using the PacBio Sequel IIe platform, producing 198.4 million subreads. From these data, we successfully reconstructed 64,260 isoforms, including 35,013 novel transcripts. For the novel isoforms, we also performed systematic examinations of their structural features, biotypes and expression profiles. This dataset expands the tobacco isoform atlas and provides a valuable resource for genome annotation and regulatory studies.
Tobacco (Nicotiana tabacum L.) is a model plant and significant cash crop in agriculture. However, it is exposed to a variety of biotic and abiotic stressors, which not only affect its growth and development but also reduce its yield and quality. In this work, tobacco extract served as a reductant for the successful green synthesis of silver nanoparticles (TE/AgNPs). Using seed medium and pot-based cultivation experiments, the effects of TE/AgNPs on tobacco growth were investigated. The results of growth and physiological measurements showed that TE/AgNPs significantly promoted tobacco growth. The molecular mechanisms by which TE/AgNPs promote tobacco growth were explored in depth by combining multi-omics techniques, such as transcriptomics, metabolomics, and microbiomics. Metabolomic analysis revealed that TE/AgNPs treatment induced a reprogramming of the plant metabolome, thereby modulating cellular metabolism and responses to external signaling molecules. These alterations primarily involved changes in organic acids, energy production, and secondary metabolites. Microbiome profiling demonstrated that TE/AgNPs treatment significantly altered the community structure of both root and soil microbiota, leading to the structure of microflora tended to be complex after treatment, and the ''network hub'' nodes of each ecological niche changed significantly. Transcriptomic analysis identified the carotenoid biosynthesis pathway as enriched among differentially expressed genes in both roots and leaves. Integrated metabolomic and transcriptomic analyses further highlighted the alanine, aspartate and glutamate metabolic pathway, as well as glutathione metabolic pathway, as playing critical roles in TE/AgNPs-promoted tobacco growth. In addition, Spearman correlation analysis was utilized to ascertain the relationship between the root differential metabolites and the ''network hub'' of the microbiome genus level co-occurrence network, and a total of 20 strongly correlated pairs were obtained. The molecular docking of the above strongly correlated pairs preliminarily proved the potential regulatory relationship between metabolites and microorganisms. Then, based on MetOrigin, the root differential metabolites were traced, and the results showed that metabolites Glycine, Cadaverine, Alanine and γ-Aminobutanoic acid are closely related to plant growth-promoting rhizobacteria (PGPR) such as Sphingobium, Sphingopyxis and Caulobacter. In conclusion, TE/AgNPs exerts its growth-promoting effects by regulating gene expression, metabolic pathways, and the inter-root microbial community in plants. This work presents new ideas and practical guidance for the adoption of sustainable and environmentally friendly agricultural production methods, as well as a theoretical foundation for the use of green-synthesized nanosilver as a plant growth regulator.
Deep learning is revolutionizing enzyme engineering through efficient residue redesign. Leveraging deep learning for enzyme engineering, we redesigned a pectinase using ProteinMPNN guided by multiple sequence alignment. Our top-performing variant, DS-5, incorporated 72 mutations and achieved an 8.9-fold increase in catalytic activity compared to the wild-type. DS-5 also displayed significantly improved thermostability, with an optimal temperature increasing by 10°C, and robust performance over a wide pH range (7.0-11.0). Structural and molecular dynamics analyses revealed the source of this enhancement: a remodeled surface electrostatic potential due to the increase of five positively charged residues, forming an extended positive groove that potentially improves substrate binding affinity. This rationally designed enzyme demonstrated superior performance in applied settings, including apple juice clarification and tobacco degradation. Furthermore, treating tobacco leaves with DS-5 substantially improved their sensory profile by elevating the concentration of desirable flavor compounds like sucrose and lactones. Our study provides a framework for deep learning-guided engineering of highly efficient enzymes, directly linking catalytic improvements to enhanced end-product quality for industrial applications.
IntroductionPlant-associated microbiota critically modulates host growth and environmental adaptation, yet assembly mechanisms, niche differentiation, and ecological strategies of bacterial communities inhabiting tobacco microhabitats remain poorly elucidated across geographical gradients.MethodsHere, we systematically characterized bacterial microbiome assembly across five tobacco-associated niches (bulk soil, rhizosphere soil, root, stem, and leaf) from seven typical tobacco-planting regions using 16S rRNA amplicon sequencing, genome annotation, and niche breadth analysis. The independent and interactive effects of geographical location and host compartment on community structure, and further compared genomic traits, functional profiles, and life-history strategies between specialist and generalist bacterial populations were quantified.ResultsThe results revealed a deterministic soil–plant continuum stratification of bacterial communities and diversity, with progressively simplified communities and decreasing alpha diversity from bulk soil to above-ground tissues, accompanied by progressive dominance of Proteobacteria. Geographical factors predominantly structured soil microbial communities via divergent edaphic properties, while host filtering acted as a universal dominant driver shaping endophytic microbiome assembly. Niche differentiation analysis demonstrated that niche-specialized bacterial ASVs overwhelmingly dominated all microhabitats and geographical sites, whereas generalist taxa only constituted auxiliary populations. Although specialist and generalist microbes exhibited highly conserved core genomic architectures and overall functional repertoires, they displayed distinct niche-specific functional divergence in metabolic pathways, stress resistance, and secondary metabolism across host compartments. Life-history strategy analysis further revealed that Y-strategist represented the core adaptive bacterial population, especially enriched in above-ground tobacco tissues.DiscussionOur study establishes a hierarchical dual-filtering assembly model for tobacco microbiota, clarifies the ecological differentiation and functional adaptation of specialist and generalist bacteria, and provides fundamental insights into the assembly rules and adaptive mechanisms of crop-associated microbiomes for future microbial resource utilization and agricultural microbiome regulation.
Acetylation serves as an effective strategy to enhance trypsin's resistance to autolysis, yet the underlying molecular mechanism remains unclear. Integrating molecular dynamics (MD) simulations and biochemical assays, we show that acetylation induces global stabilization (RMSD decreased by 0.03 nm) coupled with structural expansion (Rg increased by 0.01 nm) and a significant (p < 0.05) increase in local flexibility. These perturbations propagate allosterically to the active site, resulting in its precise structural distortion. Experimentally, acetylated trypsin exhibited markedly improved stability, retaining 80.78% of its activity after six hours of autolysis versus only 54.2% for the native enzyme, despite an initial activity reduction of 23.2%. The molecular basis for this trade-off is an allosterically rewired state that enhances structural integrity while slightly misaligning catalytic residues and promoting a low-efficiency substrate binding mode. Collectively, our work provides atomic-level insights useful for rationally designing trypsin variants with optimized performance in food enzyme engineering.
Fatty acid amide hydrolase (FAAH), an enzyme responsible for the degradation of N-acylethanolamines (NAEs), plays a crucial role in terminating the NAE signaling pathway, which is integral to plant growth and development. However, the specific role of FAAH in plant responses to cold stress remains unclear. In this study, we characterized the function of NtFAAH in tobacco (Nicotiana tabacum). Phylogenetic and sequence analyses indicated that NtFAAH shares highest homology with its Nicotiana sylvestris ortholog and clusters within the group II FAAH family. qPCR results showed that NtFAAH expression is highest in flowers and trichomes, peaking at the maturing stage. Subcellular localization analysis demonstrated that the NtFAAH-GFP fusion protein specifically localizes to the endoplasmic reticulum. Lipidomics analysis identified 130 differentially accumulated lipids between NtFAAH-silencing lines and wild-type (WT) plants, including 111 upregulated and 19 downregulated lipids. The downregulated lipids mainly comprise phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylinositol (PI), monogalactosyldiacylglycerol (MGDG), and digalactosyldiacylglycerol (DGDG). Their contents were reduced by 55.87 %, 51.65 %, 54.05 %, 89.11 %, 86.12 %, 65.27 %, 70.44 %, 65.96 %, 58.19 %, and 63.02 % respectively. Furthermore, lipid unsaturation levels of PA, PG, PC, PE, PI, and DGDG were significantly reduced in the NtFAAH RNAi lines by 10.57 %, 34.82 %, 48.17 %, 20.25 %, 13.43 %, and 18.62 % respectively. Physiological assays revealed that NtFAAH-silencing lines exhibited diminished peroxidase (POD) and catalase (CAT) activities, resulting in enhanced cold sensitivity compared to WT. Consistent with this phenotype, cold-induced expression of marker genes (NtCBF1, NtCBF3, NtCBF4, and NtGOLS1) was attenuated in silenced lines under cold stress. Collectively, these findings indicate that NtFAAH is necessary for maintaining lipid homeostasis and mediating cold stress responses in tobacco.
Cembranoid diterpenoids, as crucial secondary metabolites in tobacco, play significant physiological roles and exhibit notable biological activities, while the transcriptional regulators governing their biosynthesis remain largely unexplored. A whirly transcription factor NtWHY1 is screened out by DNA pull down using the promoter of NtCBTS (cembratrien-ol synthase), a known key gene in the pathway of cembranoid diterpenoid biosynthesis. Further experiments revealed that NtWHY1 encodes a protein with dual localization in chloroplasts and the nucleus, and it is highly transcriptionally active in tobacco's glandular trichomes and leaves. The expression level of NtWHY1 is positively correlated with the expression level of NtCBTS, as well as the products of α-cembrenediol (α-CBD) and β-cembrenediol (β-CBD), two main cembranoid diterpenoids in tobacco. We also proved that NtWHY1 can directly bind to the promoter region of NtCBTS, with evidence from chromatin immunoprecipitation (ChIP), dual-Luciferase (Dual-LUC) and electrophoretic mobility shift (EMSA) assays. Furthermore, ChIP assays have revealed that NtWHY1 silencing is correlated with reduced H3K9 acetylation and increased H3K27 methylation levels within the promoter region of NtCBTS. Collectively, our results elucidate a novel regulatory role of NtWHY1 in the biosynthesis of cembranoid diterpenoids, thereby advancing our understanding of plant secondary metabolism.
Polyphenol oxidase (PPO) is a key enzyme responsible for enzymatic browning, which significantly affects the quality and marketability of fresh-cut fruits and vegetables. 3-Mercaptopropionic acid (3-MPA) has been identified as a promising natural compound with potential anti-browning properties. This study investigated the efficacy of 3-MPA as an anti-browning agent for fresh-cut potatoes and tobacco leaf pulp. Various concentrations of 3-MPA were evaluated, with 50 mg/L identified as the optimal treatment level for inhibiting enzymatic browning while maintaining sensory quality. 3-MPA treatment enhanced antioxidant capacity, reduced PPO activity, and mitigated quinone formation in potato samples. Molecular docking simulations and dynamics analyses revealed that 3-MPA competitively binds to PPO's active site, forming a stable enzyme-inhibitor complex that effectively blocks substrate access. The inhibitory mechanism involves both direct enzyme interaction and pH reduction. 3-MPA demonstrated superior potency to conventional anti-browning agents, requiring lower concentrations for comparable effects. These findings provide insights into 3-MPA's molecular mechanism of action and establish its potential as a promising anti-browning additive for food preservation applications.
Enzymatic browning, caused by polyphenol oxidase (PPO), degrades fresh-cut produce, resulting in significant economic losses. This study investigates ethyl 3-mercaptopropionate (EMP), a safe food flavoring, as a novel PPO inhibitor. EMP at 50-100 μL/L effectively prevented browning in both fresh-cut potatoes and tobacco leaf pulp, performing comparably to the standard inhibitor sodium bisulfite but offering better safety. Purified potato PPO showed nanomolar sensitivity to EMP with an IC₅₀ of 156.7 ± 17.26 nM. Molecular modeling and dynamics simulations revealed that EMP acts as a competitive inhibitor, competing with the natural substrate for the PPO active site. By binding key active site residues, including copper-coordinating histidines, EMP induces a more rigid enzyme structure, hindering its catalytic activity. These findings establish EMP as a potent competitive inhibitor, presenting a promising, safe, and effective strategy to control enzymatic browning in fresh-cut produce. This research also provides valuable mechanistic insights for developing improved anti-browning methods.
Phosphorus (P), one of the three primary macronutrients essential for plant growth, predominantly exists in soil as unavailable forms for plant uptake. Rhizosphere bacteria can mobilize the unavailable P through two key processes: organic phosphorus mineralization and inorganic phosphorus solubilization. Despite their ecological significance, the diversity and community structure of P-mobilizing bacteria in plant rhizospheres remain insufficiently characterized. In this study, we employed culturomics to isolate bacteria from tobacco rhizosphere and systematically evaluated their P mobilization activities. The P mobilization mechanism was analyzed through whole genome sequence analyses, and the promotion effect was evaluated by greenhouse experiment. A total of 266 P mobilization bacteria were screened, representing 41.50 % of the total isolates. These bacteria were further classified as 49 genera in four phyla: Pseudomonadota (63.16 %), Bacillota (18.80 %), Bacteroidota (10.15 %), and Actinomycetota (7.89 %), with Pseudomonas (25.10 %) and Bacillus (16.47 %) as dominant genera (>10 %). The collection comprised 232 P-mineralization bacteria (PMB) (47 genera), 126 P-solubilizing bacteria (PSB) (33 genera), and 92 dual-functional (26 genera) strains. PMB strains exhibited higher α-diversity and greater numerical abundance across all sampling sites than PSB. Genomic analyses revealed that Pseudomonadota strains displayed exceptional genetic flexibility, harboring more P mobilization genes than other phyla strains. Greenhouse experiments demonstrated that PSB strains significantly enhanced tobacco seedling growth, including shoot and root biomass, stem diameter and leaf area, increased both plant P content and rhizosphere soil available P concentrations. Our study provides new insights into microbial-mediated mechanisms governing phosphorus mobilization and biogeochemical cycling within plant rhizosphere ecosystems.
Cadmium accumulation in agricultural and industrial soils necessitates the exploration of effective phytoremediation strategies. Tobacco (Nicotiana tabacum L.), a high-biomass cash crop, exhibits remarkable capacity of cadmium accumulation. However, the underlying molecular mechanisms remain poorly understood. This study employed integrated transcriptome and proteome analyses to investigate gene and protein expression profiles in tobacco shoots and roots under short-term Cd exposure. Our results showed that root cells upregulated cell wall synthesis proteins, leading to cell wall thickening and restricting cadmium transporter proteins, thereby isolating cadmium ions in the apoplast. Conversely, shoot cells exhibit a significant increase in vacuolar transporter expression, facilitating cadmium compartmentalization and mitigating cadmium toxicity. These findings highlight the tissue-synergistic accumulation strategies employed by tobacco, revealing a different molecular regulatory mechanism for cadmium accumulation at the tissue level.
BACKGROUND:Carbon nano sol (CNS) can markedly affect the plant growth and development. However, few systematic analyses have been conducted on the underlying regulatory mechanisms in plants, including tobacco (Nicotiana tabacum L.).RESULTS:Integrated analyses of phenome, ionome, transcriptome, and metabolome were performed in this study to elucidate the physiological and molecular mechanisms underlying the CNS-promoting growth of tobacco plants. We found that 0.3% CNS, facilitating the shoot and root growth of tobacco plants, significantly increased shoot potassium concentrations. Antioxidant, metabolite, and phytohormone profiles showed that 0.3% CNS obviously reduced reactive oxygen species production and increased antioxidant enzyme activity and auxin accumulation. Comparative transcriptomics revealed that the GO and KEGG terms involving responses to oxidative stress, DNA binding, and photosynthesis were highly enriched in response to exogenous CNS application. Differential expression profiling showed that NtNPF7.3/NtNRT1.5, potentially involved in potassium/auxin transport, was significantly upregulated under the 0.3% CNS treatment. High-resolution metabolic fingerprints showed that 141 and 163 metabolites, some of which were proposed as growth regulators, were differentially accumulated in the roots and shoots under the 0.3% CNS treatment, respectively.CONCLUSIONS:Taken together, this study revealed the physiological and molecular mechanism underlying CNS-mediated growth promotion in tobacco plants, and these findings provide potential support for improving plant growth through the use of CNS.
Nanomaterials have been shown to promote crop growth, yield and stress resistance. Carbon nanosol (CNS), a type of nanomaterial, is used to regulate tobacco shoot and root growth. However, information about the application of CNS to crop plants, especially tobacco, is still limited. Based on differential expression analysis and trend analysis, several miRNAs (miRN21-Novel-5p-mature, miR319b-Probable-5p-mature, miR160a-c-Known/Probable-5p-mature and miR156c-e-Known-5p-mature/star) and their target genes, including transcription factors (TFs), are likely responsible for the effect of CNS on promoting the growth of tobacco plants. In addition, we characterized nine TFs [Nitab4.5_00001789g0110 (NbbZIP), Nitab4.5_00001176g0010 (NbMYB), Nitab4.5_0001366g0010 (NbNAC), Nitab4.5_00000895g013 (NbMYB), Nitab4.5_0001225g0120 (NbNAC), Nitab4.5_0000202g0230 (NbDof), Nitab4.5_0002241g0010 (NbMYB-related), Nitab4.5_0000410g0060 (NbTCP), and Nitab4.5_0000159g0180 (NbC2H2)] associated with the response of tobacco to CNS according to the differential expression analysis, TF‒gene interaction network analysis and weighted correlation network analysis (WGCNA). Taken together, the findings of our study help understand CNS-mediated growth promotion in tobacco plants. The identification of candidate miRNAs and genes will provide potential support for the use of CNS in tobacco.
Tobacco plants (Nicotiana tabacum L.) exhibit considerable potential for phytoremediation of soil cadmium (Cd) pollutants, owing to their substantial biomass and efficient metal accumulation capabilities. The reduction of Cd accumulation in tobacco holds promise for minimizing Cd intake in individuals exposed to cigar smoking. NRAMP transporters are pivotal in the processes of Cd accumulation and resistance in plants; however, limited research has explored the functions of NRAMPs in tobacco plants. In this investigation, we focused on NtNRAMP6c, one of the three homologs of NRAMP6 in tobacco. We observed a robust induction of NtNRAMP6c expression in response to both Cd toxicity and iron (Fe) deficiency, with the highest expression levels detected in the roots. Subsequent subcellular localization and heterologous expression analyses disclosed that NtNRAMP6c functions as a plasma membrane-localized Cd transporter. Moreover, its overexpression significantly heightened the sensitivity of yeast cells to Cd toxicity. Through CRISPR-Cas9-mediated knockout of NtNRAMP6c, we achieved a reduction in Cd accumulation and an enhancement in Cd resistance in tobacco plants. Comparative transcriptomic analysis unveiled substantial alterations in the transcriptional profiles of genes associated with metal ion transport, photosynthesis, and macromolecule catabolism upon NtNRAMP6c knockout. Furthermore, our study employed plant metabolomics and rhizosphere metagenomics to demonstrate that NtNRAMP6c knockout led to changes in phytohormone homeostasis, as well as shifts in the composition and abundance of microbial communities. These findings bear significant biological implications for the utilization of tobacco in phytoremediation strategies targeting Cd pollutants in contaminated soils, and concurrently, in mitigating Cd accumulation in tobacco production destined for cigar consumption.
The changes of microbial community on tobacco leaves are affected by several factors during fermentation. However, the relative contribution of different factors in determining microbial community is not clear. This study investigated the effects of fermentation time (fermentation for 0, 3, 6, 9 and 12 months), leaf position (middle and top tobacco leaves) and fermentation site (Longyan and Xiamen warehouses) on bacterial community of tobacco leaves using 16 S rDNA sequencing. The results demonstrated that fermentation time had a much stronger impact on bacterial diversity, composition, co-occurrence network and functional profiles than leaf position and fermentation site. With the fermentation progressed, the difference of bacterial community between middle and top tobacco leaves was gradually reduced or even disappeared. The bacterial community diversity and network complexity at three, six and nine months of fermentation were significantly lower than those at fermentation initiation. Specific bacterial genera with desired functions were recruited at different fermentation stages, such as Terribacillus, Pantoea and Franconibacter at three or six months of fermentation and Pseudomonas at nine months of fermentation. The recruited microorganisms would form biofilms on tobacco leaves and compete for polysaccharide or protein substances to accelerate the degradation of tobacco macromolecular substances. In conclusion, fermentation time was an important factor in determining the composition and function of microbial community on tobacco leaves during the fermentation process.
The assembly of the rhizosphere community, even the diazotroph community, is mainly shaped by soil environmental factors (including soil climate and physiochemical characteristics) and plant selection. To better understand the driving forces on the active overall and nitrogen-fixing bacterial community compositions, we characterized the communities of tobacco rhizosphere soil collected from three sampling sites with a large geographic scale (> 600 km). The results indicate that the diversity and community composition of the overall bacterial and diazotroph communities are obviously differed according to the sampling sites. Still, no significant difference is found between the communities in rootzone and rhizosphere samples. Climate variables including mean annual precipitation (MAP) and mean annual temperature (MAT), soil physiochemical characteristics including available nitrogen (AN), available potassium (AK) and pH are main factors that affect the bacterial and diazotroph community structures in the three sampling sites. Furthermore, MAP and MAT, AN and available phosphorus (AP), total nitrogen (TN) and organic carbon (OC), AK and electrical conductivity (EC) showed similar effects, but pH showed independent effect on the composition of the overall bacteria and diazotroph communities. However, the alpha diversity indices of active overall and nitrogen-fixing bacteria in the rhizosphere are obviously higher than in the rootzone samples, and no significant differences are observed among different sampling sites. Proteobacteria is the predominant active phylum of all samples for overall and nitrogen-fixing bacteria. Escherichia-Shigella, Achromobacter, Streptomyces and Sphingomonas are the dominant active bacterial genera, and Bradyrhizobium, Skermanella and Extensimonas are dominant active nitrogen-fixing bacteria genera in rhizosphere. Furthermore, the high active abundance of Escherichia-Shigella but low abundance of Ralstonia in all three sampling sites indicate high root-knot nematode infection and low wilt disease endemic risk. These results indicate that soil environmental factors contribute more to the tobacco rhizosphere bacterial community assemblage, but the rhizosphere contributes more to the diversity of active overall bacteria and nitrogen-fixing bacteria in the community. Our study provides novel knowledge for the assemble of rhizosphere bacterial and active bacteria communities across a large geographical scale.
Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.
The study aimed at evaluating the performance of urinary exosomal prostate-specific antigen (UE-PSA) to predict the results of initial prostate biopsies and discriminate clinically significant prostate cancer (Gleason score < 7, csPCa) from nonsignificant PCa (Gleason score < 7, nsPCa) plus benign patients. Two hundred seventy-two consecutive participants were admitted who underwent a prostate biopsy. The UE-PSA expression was detected by enzyme-linked immunosorbent assay (ELISA). The predictive power and clinical value of UE-PSA was assessed by receiver operating characteristic (ROC), decision curve analysis (DCA) and waterfall plots. UE-PSA was upregulated in PCa compared to benign patients (P < .001) and csPCa compared to nsPCa plus benign patients (P < .001). UE-PSA achieved an AUC of 0.953 (0.905-0.989) in distinguishing PCa from benign patients and an AUC of 0.879 (0.808-0.941) in predicting csPCa from nsPCa plus benign patients. These results were validated in an additional multicenter cohort. In addition, DCA showed that UE-PSA achieved the highest net benefit at almost any threshold probability compared to tPSA and %fPSA. As the waterfall plot showed, the UE-PSA assay could avoid 57.6% (155 cases) and 34.6% (93 cases) unnecessary biopsies while only missing 2.6% (7 cases) and 1.5% (4 cases) of the cases of csPCa at the cutoff value of 90% and 95% sensitivity, respectively. We validated that UE-PSA presented great diagnostic power and clinical utility to diagnose PCa and csPCa. UE-PSA could be a promising noninvasive biomarker to improve PCa detection.
Background The introduction of multiparameter MRI and novel biomarkers has greatly improved the prediction of clinically significant prostate cancer (csPCa). However, decision-making regarding prostate biopsy and prebiopsy examinations is still difficult. We aimed to establish a quick and economic tool to improve the detection of csPCa based on routinely performed clinical examinations through an automated machine learning platform (AutoML). Methods This study included a multicenter retrospective cohort and two prospective cohorts with 4747 cases from 9 hospitals across China. The multimodal data, including demographics, clinical characteristics, laboratory tests, and ultrasound reports, of consecutive participants were retrieved using extract-transform-load tools. AutoML was applied to explore potential data processing patterns and the most suitable algorithm to build the Prostate Cancer Artificial Intelligence Diagnostic System (PCAIDS). The diagnostic performance was determined by the receiver operating characteristic curve (ROC) for discriminating csPCa from insignificant prostate cancer (PCa) and benign disease. The clinical utility was evaluated by decision curve analysis (DCA) and waterfall plots. Results The random forest algorithm was applied in the feature selection, and the AutoML algorithm was applied for model establishment. The area under the curve (AUC) value in identifying csPCa was 0.853 in the training cohort, 0.820 in the validation cohort, 0.807 in the Changhai prospective cohort, and 0.850 in the Zhongda prospective cohort. DCA showed that the PCAIDS was superior to PSA or fPSA/tPSA for diagnosing csPCa with a higher net benefit for all threshold probabilities in all cohorts. Setting a fixed sensitivity of 95%, a total of 32.2%, 17.6%, and 26.3% of unnecessary biopsies could be avoided with less than 5% of csPCa missed in the validation cohort, Changhai and Zhongda prospective cohorts, respectively. Conclusions The PCAIDS was an effective tool to inform decision-making regarding the need for prostate biopsy and prebiopsy examinations such as mpMRI. Further prospective and international studies are warranted to validate the findings of this study. Trial registration Chinese Clinical Trial Registry ChiCTR2100048428. Registered on 06 July 2021.