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1.
Artigo em Inglês | MEDLINE | ID: mdl-38986448

RESUMO

The segmentation of atrial scars in LGE-MRI images has huge potential value for clinical diagnosis and subsequent treatment. In clinical practice, atrial scars are usually manually calibrated by experienced experts, which is time-consuming and prone to errors. However, automatic segmentation also faces difficulties due to myocardial scars' small size and variable shape. The present study introduces a dual branch network, incorporating edge attention, and deep supervision strategy. Edge attention is introduced to fully utilize the spatial relationship between the scar and the atrium. Besides, dense attention is embedded in bottom layer to solve feature disappearance. At the same time, deep supervision accelerates the convergence of the model and improves segmentation accuracy. The experiments were conducted on the 2022 atrial and scar segmentation challenge dataset. The results demonstrate that the proposed method has achieved superior performance.

2.
J Psychosom Res ; 184: 111858, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018767

RESUMO

AIM: Some studies and societal discussions have suggested a potential link between overweight and a higher risk of mental disorders and suicidal ideation. However, the causal relationships between these factors remain unclear. This study aims to assess the bidirectional causal associations between overweight and mental disorders, including suicidal attempts. METHOD: We conducted a Two-Sample Mendelian Randomization study utilizing data from over 450,000 individuals of European ancestry sourced from a comprehensive Genome-Wide Association Study database. We chose single-nucleotide polymorphisms as instrumental variables. RESULTS: Our analyses consistently supported a unidirectional causal association of overweight with the increased risk of major depressive disorder (MDD, ß = 0.152, se = 0.069, P = 0.027), bipolar affective disorders (BD, ß = 0.197, se = 0.092, P = 0.033), and attention-deficit / hyperactivity disorder (ADHD, ß = 0.308, se = 0.080, P = 1.366 × 10-4). We observed no significant causal relationships for the exposure of overweight to anxiety disorder (AD), manic episode (MA), panic disorder (PD), schizophrenia (SZ), substance use disorder (SUD), autism spectrum disorder (ASD), ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events. CONCLUSION: This study has provided evidence for the causal relationship between overweight and MDD, BD, ADHD, with no observed relationship between overweight and AD, MA, PD, SZ, SUD, ASD, ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events.

3.
Medicine (Baltimore) ; 103(26): e38541, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941416

RESUMO

INTRODUCTION: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Feminino , Idoso , Imunoterapia Adotiva/métodos
4.
Sensors (Basel) ; 24(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38894438

RESUMO

Accurate identification of Seriola dumerili (SD) offers crucial technical support for aquaculture practices and behavioral research of this species. However, the task of discerning S. dumerili from complex underwater settings, fluctuating light conditions, and schools of fish presents a challenge. This paper proposes an intelligent recognition model based on the YOLOv8 network called SD-YOLOv8. By adding a small object detection layer and head, our model has a positive impact on the recognition capabilities for both close and distant instances of S. dumerili, significantly improving them. We construct a convenient S. dumerili dataset and introduce the deformable convolution network v2 (DCNv2) to enhance the information extraction process. Additionally, we employ the bottleneck attention module (BAM) and redesign the spatial pyramid pooling fusion (SPPF) for multidimensional feature extraction and fusion. The Inner-MPDIoU bounding box regression function adjusts the scale factor and evaluates geometric ratios to improve box positioning accuracy. The experimental results show that our SD-YOLOv8 model achieves higher accuracy and average precision, increasing from 89.2% to 93.2% and from 92.2% to 95.7%, respectively. Overall, our model enhances detection accuracy, providing a reliable foundation for the accurate detection of fishes.


Assuntos
Algoritmos , Animais , Peixes , Redes Neurais de Computação , Aquicultura/métodos
5.
Sci Adv ; 10(23): eadl6083, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838151

RESUMO

Hepatocellular carcinoma (HCC) acquires an immunosuppressive microenvironment, leading to unbeneficial therapeutic outcomes. Hyaluronan-mediated motility receptor (HMMR) plays a crucial role in tumor progression. Here, we found that aberrant expression of HMMR could be a predictive biomarker for the immune suppressive microenvironment of HCC, but the mechanism remains unclear. We established an HMMR-/- liver cancer mouse model to elucidate the HMMR-mediated mechanism of the dysregulated "don't eat me" signal. HMMR knockout inhibited liver cancer growth and induced phagocytosis. HMMRhigh liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMRhighCD47high expression showed a worse prognosis than those with HMMRlowCD47low expression. HMMR formed a complex with FAK/SRC in the cytoplasm to activate NF-κB signaling, which could be independent of membrane interaction with CD44. Notably, targeting HMMR could enhance anti-PD-1 treatment efficiency by recruiting CD8+ T cells. Overall, our data revealed a regulatory mechanism of the "don't eat me" signal and knockdown of HMMR for enhancing anti-PD-1 treatment.


Assuntos
Antígeno CD47 , Carcinoma Hepatocelular , Receptores de Hialuronatos , Neoplasias Hepáticas , Fagócitos , Fagocitose , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Antígeno CD47/metabolismo , Antígeno CD47/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/genética , Evasão da Resposta Imune , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Camundongos Knockout , NF-kappa B/metabolismo , Fagócitos/metabolismo , Fagócitos/imunologia , Transdução de Sinais , Evasão Tumoral , Microambiente Tumoral/imunologia
6.
Curr Biol ; 34(9): R452-R472, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38714177

RESUMO

Forest restoration is being scaled up globally, carrying major expectations of environmental and societal benefits. Current discussions on ensuring the effectiveness of forest restoration are predominantly focused on the land under restoration per se. But this focus neglects the critical issue that land use and its drivers at larger spatial scales have strong implications for forest restoration outcomes, through the influence of landscape context and, importantly, potential off-site impacts of forest restoration that must be accounted for in measuring its effectiveness. To ensure intended restoration outcomes, it is crucial to integrate forest restoration into land-use planning at spatial scales large enough to account for - and address - these larger-scale influences, including the protection of existing native ecosystems. In this review, we highlight this thus-far neglected issue in conceptualizing forest restoration for the delivery of multiple desirable benefits regarding biodiversity and ecosystem services. We first make the case for the need to integrate forest restoration into large-scale land-use planning, by reviewing current evidence on the landscape-level influences and off-site impacts pertaining to forest restoration. We then discuss how science can guide the integration of forest restoration into large-scale land-use planning, by laying out key features of methodological frameworks required, reviewing the extent to which existing frameworks carry these features, and identifying methodological innovations needed to bridge the potential shortfall. Finally, we critically review the status of existing methods and data to identify future research efforts needed to advance these methodological innovations and, more broadly, the effective integration of forest restoration design into large-scale land-use planning.


Assuntos
Conservação dos Recursos Naturais , Florestas , Conservação dos Recursos Naturais/métodos , Agricultura Florestal/métodos , Biodiversidade , Ecossistema , Recuperação e Remediação Ambiental/métodos
7.
Angew Chem Int Ed Engl ; 63(29): e202406218, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38752878

RESUMO

Transition metal-catalyzed carbene transfer reactions have a century-old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two-electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem-dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons-Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal 1,1-dehydrogenation. These reactions are currently restricted to substrates containing electron-withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion.

8.
IEEE Open J Eng Med Biol ; 5: 54-58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487094

RESUMO

Goal: Distance information is highly requested in assistive smartphone Apps by people who are blind or low vision (PBLV). However, current techniques have not been evaluated systematically for accuracy and usability. Methods: We tested five smartphone-based distance-estimation approaches in the image center and periphery at 1-3 meters, including machine learning (CoreML), infrared grid distortion (IR_self), light detection and ranging (LiDAR_back), and augmented reality room-tracking on the front (ARKit_self) and back-facing cameras (ARKit_back). Results: For accuracy in the image center, all approaches had <±2.5 cm average error, except CoreML which had ±5.2-6.2 cm average error at 2-3 meters. In the periphery, all approaches were more inaccurate, with CoreML and IR_self having the highest average errors at ±41 cm and ±32 cm respectively. For usability, CoreML fared favorably with the lowest central processing unit usage, second lowest battery usage, highest field-of-view, and no specialized sensor requirements. Conclusions: We provide key information that helps design reliable smartphone-based visual assistive technologies to enhance the functionality of PBLV.

9.
Org Lett ; 26(11): 2169-2174, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38477516

RESUMO

Carbonyl compounds are widely found in various pharmaceutical intermediates and synthetic precursors. Herein we report a simple light-driven three-component aryl halide process for synthesizing a variety of carbonylation products, utilizing Co2(CO)8 as an abundant solid carbonyl source, in good to excellent yields. The products can easily be subjected to further functionalization in synthesis. Mechanism studies indicated that this reaction is enabled by aryl radical generation and the subsequent CO insertion, alkene insertion, and protonation process.

10.
Environ Int ; 185: 108523, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484610

RESUMO

Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox-LDPE) and established a model of MPs exposure by continuously orally gavage of C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days with or without oral administration of Lactobacillus plantarum DP189 and galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs or Ox-LDPE-MPs caused several adverse effects in mice, mainly manifested by behavioral changes, disruption of the intestinal and blood-brain barrier (BBB), and simultaneous oxidative stress, inflammatory reactions, and pathological damage in the brain and intestines. Brain transcriptomic analysis revealed that the cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after exposure to LDPE-MPs or Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction and Western Blotting results further demonstrated that the critical genes (Slc5a7, Chat and Slc18a3) and proteins (Chat and Slc18a3) in the cholinergic synaptic signaling pathway were significantly down-regulated after exposure to LDPE-MPs or Ox-LDPE-MPs. These alterations lead to reduced acetylcholine concentration, which causes cognitive dysfunction in mice. Importantly, the DP189&GOS interventions effectively mitigated the MPs-induced cognitive dysfunction and intestinal microbiota alteration, improved intestinal and BBB integrity, attenuated the oxidative stress and inflammatory response, and also saw a rebound in the release of acetylcholine. These results indicated that LDPE-MPs and Ox-LDPE-MPs exert neurotoxic effects on mice by inducing oxidative stress, inflammatory responses, and dysregulation of cholinergic signaling pathways in the mouse brain. That probiotic supplementation is effective in attenuating MPs-induced neurotoxicity in mice. Overall, this study reveals the potential mechanisms of neurotoxicity of LDPE-MPs and Ox-LDPE-MPs on mice and their improvement measures, necessary to assess the potential risks of plastic contaminants to human health.


Assuntos
Microplásticos , Polietileno , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Plásticos , Eixo Encéfalo-Intestino , Acetilcolina , Colinérgicos
11.
IEEE Trans Med Imaging ; PP2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530716

RESUMO

Cancer is widely recognized as the primary cause of mortality worldwide, and pathology analysis plays a pivotal role in achieving accurate cancer diagnosis. The intricate representation of features in histopathological images encompasses abundant information crucial for disease diagnosis, regarding cell appearance, tumor microenvironment, and geometric characteristics. However, recent deep learning methods have not adequately exploited geometric features for pathological image classification due to the absence of effective descriptors that can capture both cell distribution and gathering patterns, which often serve as potent indicators. In this paper, inspired by clinical practice, a Hierarchical Graph Pyramid Transformer (HGPT) is proposed to guide pathological image classification by effectively exploiting a geometric representation of tissue distribution which was ignored by existing state-of-the-art methods. First, a graph representation is constructed according to morphological feature of input pathological image and learn geometric representation through the proposed multi-head graph aggregator. Then, the image and its graph representation are feed into the transformer encoder layer to model long-range dependency. Finally, a locality feature enhancement block is designed to enhance the 2D local representation of feature embedding, which is not well explored in the existing vision transformers. An extensive experimental study is conducted on Kather-5K, MHIST, NCT-CRC-HE, and GasHisSDB for binary or multi-category classification of multiple cancer types. Results demonstrated that our method is capable of consistently reaching superior classification outcomes for histopathological images, which provide an effective diagnostic tool for malignant tumors in clinical practice.

12.
J Org Chem ; 89(7): 5189-5199, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38511413

RESUMO

The synthesis of ketones has been a long focus of chemistry research, on account of its unique reactivity. Herein, we report a simple light-driven photocatalyst-free synthesis of ß, δ-functionalized ketones from aldehydes, using inexpensive and commercially abundant feedstock chemicals. This reaction is enabled by the direct acyl radical generation via hydrogen atom transfer and the subsequent radical addition process, avoiding the need for prefunctionalized substrates and organometallic reagent.

14.
Front Neurorobot ; 18: 1353879, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405087

RESUMO

Introduction: An accurate inverse dynamics model of manipulators can be effectively learned using neural networks. However, further research is required to investigate the impact of spatiotemporal variations in manipulator motion sequences on network learning. In this work, the Velocity Aware Spatial-Temporal Attention Residual LSTM neural network (VA-STA-ResLSTM) is proposed to learn a more accurate inverse dynamics model, which uses a velocity-aware spatial-temporal attention mechanism to extract dynamic spatiotemporal features selectively from the motion sequence of the serial manipulator. Methods: The multi-layer perception (MLP) attention mechanism is adopted to capture the correlation between joint position and velocity in the motion sequence, and the state correlation between hidden units in the LSTM network to reduce the weight of invalid features. A velocity-aware state fusion approach of LSTM network hidden units' states is proposed, which utilizes variation in joint velocity to adapt to the temporal characteristics of the manipulator dynamic motion, improving the generalization and accuracy of the neural network. Results: Comparative experiments have been conducted on two open datasets and a self-built dataset. Specifically, the proposed method achieved an average accuracy improvement of 61.88% and 43.93% on the two different open datasets and 71.13% on the self-built dataset compared to the LSTM network. These results demonstrate a significant advancement in accuracy for the proposed method. Discussion: Compared with the state-of-the-art inverse dynamics model learning methods of manipulators, the modeling accuracy of the proposed method in this paper is higher by an average of 10%. Finally, by visualizing attention weights to explain the training procedure, it was found that dynamic modeling only relies on partial features, which is meaningful for future optimization of inverse dynamic model learning methods.

15.
Sci Total Environ ; 912: 169075, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38056662

RESUMO

As a fundamental transportation mode, maritime logistics has become an indispensable component on a global scale. However, there are multiple drawbacks associated with ports operating in traditional ways, such as higher cost, lower efficiency and generating more environmental pollution. Digital technologies have been researched and implemented gradually in green ports, especially in data collection and real-time monitoring, and these advances help to promote higher work efficiency and reduce detrimental environmental impacts. It was found that green ports (e.g. ports of Raffina, Los Angeles, and Long Beach) generally perform better in energy conservation and pollutant emission reduction. However, considering the variability in the level of digitalization, there are challenges in achieving effective communications between individual ports. Therefore, to optimize and update green port practices, a systematic review is necessary to comprehensively analyze the beneficial contributions of green ports. This review adopted bibliometric analysis to examine the shipping framework focusing on green ports digitalization and innovation. After that, with regards to the bibliometric results, five aspects were analyzed, including environment, performance, policy, technology, and management. Besides, intelligent life-cycle management was systematically discussed to improve green ports and maritime logistics performance and sustainability in three aspects, namely waste discharge, shipping management system and green ports management. The findings revealed that green ports and maritime logistics require digital cooperation, transformation, and management to achieve sustainable development goals, including route selection and control of ships' numbers, weather prediction, and navigational effluent monitoring, albeit with some obstacles.

16.
Zhongguo Fei Ai Za Zhi ; 26(11): 843-850, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38061886

RESUMO

BACKGROUND: The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. METHODS: Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. RESULTS: A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. CONCLUSIONS: Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.


Assuntos
Neoplasias Pulmonares , Masculino , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Qualidade de Vida , Cirurgia Torácica Vídeoassistida/efeitos adversos , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
17.
Nat Commun ; 14(1): 8392, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110372

RESUMO

Early diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Here, we describe a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 1002 individuals. Machine learning model determined as P4 panel (HABP2, CD163, AFP and PIVKA-II) clearly distinguish HCC from liver cirrhosis (LC, AUC 0.979, sensitivity 0.925, specificity 0.915) and healthy individuals (HC, AUC 0.992, sensitivity 0.975, specificity 1.000) in an independent validation cohort, outperforming existing clinical prediction strategies. Furthermore, the P4 panel can accurately predict LC to HCC conversion (AUC 0.890, sensitivity 0.909, specificity 0.877) with predicting HCC at a median of 11.4 months prior to imaging in prospective external validation cohorts (No.: Keshen 2018_005_02 and NCT03588442). These results suggest that proteomics-driven serum biomarker discovery provides a valuable reference for the liquid biopsy, and has great potential to improve early diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores Tumorais , Proteômica , Estudos Prospectivos , alfa-Fetoproteínas/metabolismo , Biomarcadores , Detecção Precoce de Câncer/métodos
18.
Chem Sci ; 14(42): 11761-11767, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37920336

RESUMO

The direct functionalization of inert C-H bonds has long been a "holy grail" for the chemistry world. In this report, the direct C(sp3)-N bond formation of unactivated alkanes is reported with a GaN based Mott-Schottky catalyst under photocatalytic reaction conditions. Long term stability and reaction efficiency (up to 92%) were achieved with this photocatalyst. The deposition of a Pd co-catalyst on the surface of GaN significantly enhanced the reaction efficiency. Microscopic investigation suggested a remarkable interaction in the Pd/GaN Schottky junction, giving a significant Pd/GaN depletion layer. In addition, density functional theory (DFT) calculations were performed to show the distinct performance of Pd nanoparticles at the atomic level.

19.
Front Plant Sci ; 14: 1216702, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868314

RESUMO

Background: Nicotiana tabacum is an important economic crop, which is widely planted in the world. Lignin is very important for maintaining the physiological and stress-resistant functions of tobacco. However, higher lignin content will produce lignin gas, which is not conducive to the formation of tobacco quality. To date, how to precisely fine-tune lignin content or composition remains unclear. Results: Here, we annotated and screened 14 CCoAOMTs in Nicotiana tabacum and obtained homozygous double mutants of CCoAOMT6 and CCoAOMT6L through CRSIPR/Cas9 technology. The phenotype showed that the double mutants have better growth than the wild type whereas the S/G ratio increased and the total sugar decreased. Resistance against the pathogen test and the extract inhibition test showed that the transgenic tobacco has stronger resistance to tobacco bacterial wilt and brown spot disease, which are infected by Ralstonia solanacearum and Alternaria alternata, respectively. The combined analysis of metabolome and transcriptome in the leaves and roots suggested that the changes of phenylpropane and terpene metabolism are mainly responsible for these phenotypes. Furthermore, the molecular docking indicated that the upregulated metabolites, such as soyasaponin Bb, improve the disease resistance due to highly stable binding with tyrosyl-tRNA synthetase targets in Ralstonia solanacearum and Alternaria alternata. Conclusions: CAFFEOYL-COA 3-O-METHYLTRANSFERASE 6/6L can regulate the S/G ratio of lignin monomers and may affect tobacco bacterial wilt and brown spot disease resistance by disturbing phenylpropane and terpene metabolism in leaves and roots of Nicotiana tabacum, such as soyasaponin Bb.

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