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Myocardial ischemia is a disease characterized by high morbidity and mortality rates, restoring blood supply to the ischemic area through reperfusion is an effective intervention method. However, numerous studies have shown that reperfusion may cause severe myocardial damage, resulting in myocardial systolic and diastolic dysfunction and seriously affecting myocardial function. This phenomenon is called myocardial ischemia reperfusion injury(MIRI). The physiological and pathological mechanisms of MIRI include oxidative stress, calcium overload, autophagy, pyrolysis, endoplasmic reticulum stress, apoptosis, etc. Oxidative stress plays an important role in MIRI-related cell death and is considered to be the main mechanism of MIRI. The occurrence of oxidative stress is mainly due to the excessive production of reactive oxygen species(ROS), which disrupts the balance of the redox system of the body or tissue. A large number of highly reactive ROS exceed the antioxidant defense capacity of cardiomyocytes, causing modifications in biological macromolecules such as DNA and proteins and resulting in severe reactions like DNA damage, protein dysfunction, cell damage or death, and local inflammation. Oxidative stress mediates apoptosis, autophagy, and inflammatory injury through various pathways, resulting in irreversible cardiomyocyte injury and myocardial dysfunction, which brings significant challenges for clinical treatment and prognosis. In recent years, remarkable progress has been made in understanding oxidative stress in ischemia reperfusion(I/R) injury of different organs and tissue. However, the injury mechanism caused by oxidative stress in restoring blood supply to the ischemic area and the protective effect of TCM remain largely unexplored. This article reviewed the role of oxidative stress in MIRI, the main production pathways of ROS, and the protective effects of TCM on oxidative stress injury during ischemic myocardial reperfusion, so as to provide a reference for future research and clinical treatment in this field.
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Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão Miocárdica , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Substâncias Protetoras/farmacologiaRESUMO
BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.
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Bacillus subtilis , Células Matadoras Naturais , Animais , Camundongos , Células Matadoras Naturais/metabolismo , Linfócitos T/metabolismo , Interferon gama , FagocitoseRESUMO
Upconversion (UC) is a fascinating anti-Stokes-like optical process with promising applications in diverse fields. However, known UC mechanisms are mainly based on direct energy transfer between metal ions, which constrains the designability and tunability of the structures and properties. Here, we synthesize two types of Ln8L12-type (Ln for lanthanide ion; L for organic ligand L1 or L2R/S) lanthanide-organic complexes with assembly induced excited-multimer states. The Yb8(L2R/S)12 assembly exhibits upconverted multimer green fluorescence under 980 nm excitation through a cooperative sensitization process. Furthermore, upconverted red emission from Eu3+ on the heterometallic (Yb/Eu)8L12 assemblies is also realized via excited-multimer mediated energy relay. Our findings demonstrate a new strategy for designing UC materials, which is crucial for exploiting photofunctions of multicomponent lanthanide-organic complexes.
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A straightforward electrochemical protocol for efficient hydrogenation of unsaturated CîC bonds has been reported in an undivided cell. A series of versatile 1,4-diketones are smoothly generated under metal-free and external-reductant-free electrolytic conditions. Moreover, the tolerance of various functional groups and decagram-scale experiments have shown the practicability and potential applications of this methodology. Moreover, a range of heterocyclic compounds were easily prepared through follow-up procedures of 1,4-diketones.
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Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 â, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Benchmarking , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem/métodosRESUMO
Astragali Radix is one of traditional Chinese medicines with effects in invigorating Qi for consolidating superficies, inducing diuresis to alleviate edema, promoting pus discharge and tissue regeneration. In recent years, the traditional Chinese medicine fermentation technology has received extensive attentions due to its high efficiency and safety. The pharmacological functions of traditional Chinese medicines could be further enhanced after microbial fermentation, which has a broad development prospects. In this paper, we summarized relevant literatures of Astragali Radix fermentation in such aspects as fermentation strains, fermentation forms, process optimization, active ingredients and pharmacological effects, in the expectation of providing a reference for development and utilization of Astragali Radix.
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Astrágalo , Medicamentos de Ervas Chinesas , Fermentação , Medicina Tradicional Chinesa , Raízes de PlantasRESUMO
The stability of a battery is strongly dependent on the feature of solid electrolyte interphase (SEI). The electrical double layer forms prior to the formation of SEI at the interface between the Li metal anode and the electrolyte. The fundamental understanding on the regulation of the SEI structure and stability on Li surface through the structure of the electrical double layer is highly necessary for safe batteries. Herein, the interfacial chemistry of the SEI is correlated with the initial Li surface adsorption electrical double layer at the nanoscale through theoretical and experimental analysis. Under the premise of the constant solvation sheath structure of Li+ in bulk electrolyte, a trace amount of lithium nitrate (LiNO3) and copper fluoride (CuF2) were employed in electrolytes to build robust electric double layer structures on a Li metal surface. The distinct results were achieved with the initial competitive adsorption of bis(fluorosulfonyl)imide ion (FSI-), fluoride ion (F-), and nitrate ion (NO3-) in the inner Helmholtz plane. As a result, Cu-NO3- complexes are preferentially adsorbed and reduced to form the SEI. The modified Li metal electrode can achieve an average Coulombic efficiency of 99.5% over 500 cycles, enabling a long lifespan and high capacity retention of practical rechargeable batteries. The as-proposed mechanism bridges the gap between Li+ solvation and the adsorption about the electrode interface formation in a working battery.
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High mobility group AT-hook 1 (HMGA1) is able to regulate gene expression and function as a tumour suppressor. The spatiotemporal expression pattern of HMGA1 was investigated in this study. Immature female rats (22-23 days old) were treated with 10IU, s.c., pregnant mare's serum gonadotrophin to stimulate follicular development, followed 48h later by injection with 5IU, s.c., human chorionic gonadotrophin (hCG). Whole ovaries or granulosa cells were collected at various times after hCG administration (n=3 per time point). Real-time polymerase chain reaction and western blot analysis revealed that HMGA1 was highly stimulated in the ovary by 4-12h after hCG treatment. In situ hybridisation analysis demonstrated that Hmga1 mRNA expression was induced in granulosa cells between 8 and 12h after hCG treatment. There was negligible Hmga1 mRNA signal observed in newly forming corpora lutea. In addition, the data indicated that both the protein kinase (PK) A and PKC pathways regulated Hmga1 expression in rat granulosa cells. In rat granulosa cell cultures, upregulation of Hmga1 was dependent on new protein synthesis because Hmga1 was inhibited by cycloheximide. Furthermore, Hmga1 mRNA expression in rat granulosa cell cultures was inhibited by AG1478, whereas NS398 and RU486 had no effect, suggesting that Hmga1 expression was regulated, in part, by the epidermal growth factor pathway. In summary, the findings of this study suggest that induction of Hmga1 may be important for theca and granulosa cell differentiation into luteal cells.
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Diferenciação Celular/fisiologia , Proteína HMGA1a/metabolismo , Luteinização/metabolismo , Ovário/metabolismo , Ovulação/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/metabolismo , Feminino , Regulação da Expressão Gênica , Gonadotropinas Equinas/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Proteína HMGA1a/genética , Luteinização/efeitos dos fármacos , Luteinização/genética , Ovulação/efeitos dos fármacos , Ovulação/genética , Ratos , Ratos Sprague-Dawley , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismoRESUMO
The intrinsic instability of organic electrolytes seriously impedes practical applications of high-capacity metal (Li, Na) anodes. Ion-solvent complexes can even promote the decomposition of electrolytes on metal anodes. Herein, first-principles calculations were performed to investigate the origin of the reduced reductive stability of ion-solvent complexes. Both ester and ether electrolyte solvents are selected to interact with Li+ , Na+ , K+ , Mg2+ , and Ca2+ . The LUMO energy levels of ion-ester complexes exhibit a linear relationship with the binding energy, regulated by the ratio of carbon atomic orbital in the LUMO, while LUMOs of ion-ether complexes are composed by the metal atomic orbitals. This work shows why ion-solvent complexes can reduce the reductive stability of electrolytes, reveals different mechanisms for ester and ether electrolytes, and provides a theoretical understanding of the electrolyte-anode interfacial reactions and guidance to electrolyte and metal anode design.
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Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 µg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection.
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Antivirais/farmacologia , Ácidos Cafeicos/farmacologia , Vírus da Cinomose Canina/efeitos dos fármacos , Cinomose/tratamento farmacológico , Animais , Antivirais/administração & dosagem , Antivirais/química , Antivirais/uso terapêutico , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/química , Ácidos Cafeicos/uso terapêutico , Chlorocebus aethiops , Cinomose/virologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Concentração Inibidora 50 , RNA Viral/metabolismo , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Fatores de Tempo , Células Vero/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Zinc pyrithione (ZPT) is a broad-spectrum antibacterial and antifungal agent; therefore, it is widely used in industry and civilian life. It is discharged into the aquatic environment with industrial and civilian waste water. Carassius sp. is one of the most widely distributed and farmed fish in China. The effects of aquatic ZPT on Carassius sp. remain unknown. In this study, we determined the acute toxicity of ZPT on Carassius sp. The results showed that the median lethal concentration (LC50 96 h) of ZPT on Carassius sp. cultivated in freshwater or water with 1.5 or 3 salinity was 0.163, 0.126, and 0.113 mg/L, respectively. ZPT has a higher affinity to the liver than the kidney, with a prolonged tissue residual time. P-glycoprotein (P-gp), an ATP-binding cassette transporter, was found to be induced in the liver and kidney tissues of these Carassius spp. after ZPT treatment, based on the determination of its mRNA and protein levels by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The ZPT accumulation and magnitude of P-gp induction were also affected by the salinity of the cultivation water. These results suggest that aquatic ZPT is potentially toxic to Carassius sp. We speculate that P-gp induction may play a protective role for Carassius sp. Our findings provide a basis for assessing the potential risk of ZPT to aquatic animals including Carassius sp.
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Antibacterianos/toxicidade , Antifúngicos/toxicidade , Carpa Dourada , Compostos Organometálicos/toxicidade , Piridinas/toxicidade , Poluentes Químicos da Água/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antibacterianos/farmacocinética , Antifúngicos/farmacocinética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Carpa Dourada/genética , Carpa Dourada/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Compostos Organometálicos/farmacocinética , Piridinas/farmacocinética , RNA Mensageiro/metabolismo , Poluentes Químicos da Água/farmacocinéticaRESUMO
Stress cardiomyopathy is an atypical myocardial disease induced by emotional or physical stress, with the characteristic of left ventricular systolic dysfunction, transient imaging and electrocardiogram (ECG) changes. Sudden cardiac death can occur in severe cases. Clinical symptoms are likely to appear on acute myocardial infarction, but the exact pathological mechanism is unclear. In the present study, we perform a systematic review of the literature on the clinical manifestations, epidemiological characteristics, ECG, imaging and laboratory tests of stress cardiomyopathy, in order to provide the values for forensic pathology diagnosis.
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Morte Súbita Cardíaca , Estresse Psicológico , Cardiomiopatia de Takotsubo/fisiopatologia , Diagnóstico por Imagem , Eletrocardiografia , Humanos , Infarto do MiocárdioRESUMO
Two new alkaloids, lycosprenine (1) and 2α-methoxy-6-O-methyllycorenine (2), along with 22 known alkaloids (3-23b), were isolated from the bulb of Lycoris sprengeri. Their structures were elucidated on the basis of spectral analysis and by comparison of the spectroscopic data with those of known compounds. Selected compounds (1-3 and 6-9) were tested for their neuroprotective activities against H2O2-, CoCl2- and Aß25-35-induced SH-SY5Y cell injury, most of which exhibited neuroprotective effects of different degrees.
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Alcaloides/isolamento & purificação , Lycoris/química , Fármacos Neuroprotetores/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Raízes de Plantas/químicaRESUMO
Previous studies have reported the relationship between educational attainment and attention deficit hyperactivity disorder (ADHD). However, the mechanism of this relationship remains unknown. It is well known that educational attainment correlates with income. Therefore, based on summary data from a genome-wide association study we used two-step Mendelian randomization (MR) to explore the role of income between education and ADHD. The inverse variance weighted (IVW) method was used in our analysis. The IVW results suggested that educational attainment and income were protective factors against ADHD. Educational attainment affects ADHD through income [ADHD: Beta = -0.68, 95% confidence interval (CI) = -0.87, -0.49; female: Beta = -0.87, 95% CI = -1.28, -0.47; male: Beta = -1.01, 95% CI = -1.34, -0.68; childhood: Beta = -0.52, 95% CI = -0.74, -0.30; late-diagnosed: Beta = -0.78, 95% CI = -1.11, -0.47; persistent: Beta = -0.82, 95% CI = -1.33, -0.31]. Income also affected ADHD through educational attainment [female: Beta = -1.08, 95% CI = -1.35, -0.83; male: Beta = -1.16, 95% CI = -1.57, -0.77; persistent: Beta = -1.48, 95% CI = -2.09, -0.94]. In the final analysis, data with heterogeneity were analyzed using IVW random effects results. The mechanism is that income will mediate the relationship between educational attainment and ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Masculino , Feminino , Criança , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Análise de Mediação , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana/métodos , EscolaridadeRESUMO
Defects on nanomaterials can effectively enhance the performance of electrochemical detection, but an excessive number of defects may have an adverse effect. In this study, MoS2 nanosheets were synthesized using a hydrothermal synthesis method. By controlling the calcination temperature, MoS2-7H, calcined at 700 °C under H2/Ar2, exhibited an optimal ratio of "point" defects to "plane" defects, resulting in excellent detection performance for mercury ions (Hg(II)). In general, the sulfur vacancies (SV) and undercoordinated Mo generated after calcination of MoS2 significantly promotes the adsorption process and redox of Hg(II) by increasing surface chemical activity, providing additional adsorption sites and adjusting surface charge status to accelerate the catalytic redox of Hg(II). The prepared MoS2-7H-modified electrode showed a sensitivity of 18.25 µA µM-1 and a low limit of detection (LOD) of 6.60 nM towards Hg(II). MoS2-7H also demonstrated a good anti-interference, stability, and exhibited a strong current response in real water samples. The modulation to obtain appropriate number of defects in MoS2 holds promise as a prospective electrode modification material for the electroanalysis.
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The first straightforward strategy for the synthesis of 1,4-dicarbonyl Z-alkenes has been developed via an electrochemical cross-coupling reaction of sulfoxonium ylides and alkynes with water. The metal-free protocol showed an easy-to-handle nature, good functional group tolerance, and high Z-stereoselectivity, which is rare in previous cases. The proposed reaction mechanism was convincingly established by carrying out a series of control experiments, cyclic voltammetry experiments, and density functional theory (DFT) studies.
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With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug-tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 µM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 µM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta-position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure-activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.
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Candida auris , Candida , Compostos de Sulfonilureia , Humanos , Antifúngicos/farmacologia , Relação Estrutura-Atividade , Testes de Sensibilidade MicrobianaRESUMO
Drought dramatically affects plant growth and yield. A previous study indicated that endophytic fungus Phomopsis liquidambaris can improve the drought resistance of peanuts, which is related with the root arbuscular mycorrhizal fungi (AMF) community; however, how root endophytes mediate AMF assembly to affect plant drought resistance remains unclear. Here, we explored the mechanism by which endophytic fungus recruits AMF symbiotic partners via rhizodeposits to improve host drought resistance. The results showed that Ph. liquidambaris enhanced peanut drought resistance by enriching the AMF genus Claroideoglomus of the rhizosphere. Furthermore, metabolomic analysis indicated that Ph. liquidambaris significantly promoted isoformononetin and salicylic acid (SA) synthesis in rhizodeposits, which were correlated with the increase in Claroideoglomus abundance following Ph. liquidambaris inoculation. Coinoculation experiments confirmed that isoformononetin and SA could enrich Claroideoglomus etunicatum in the rhizosphere, thereby improving the drought resistance. This study highlights the crucial role of fungal consortia in plant stress resistance.
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Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data, and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling, and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment, and jasmonic acid-mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome and that depletion of key protective microbial community promotes the fruit disease incidence.