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1.
Talanta ; 225: 121963, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592717

RESUMO

Development of simple, robust, and reliable detection strategy of disease biomarkers holds tremendous promise for early clinical diagnosis and prognosis of diseases. In this work, through combining a silver nanoparticle (AgNP) linked immunoassay and aggregation induced emission (AIE)-based fluorogenic Ag+ probe, we developed a silver-amplified fluorescence immunoassay for the detection of disease biomarkers. This method overcame the intrinsic limitations of enzymes as the dissolution of AgNPs generated numerous Ag+, which could switch on the fluorogenic Ag+ probe driven by tetrazolate-Ag+ complexation. As a proof of concept, our method could be used for determining α-fetoprotein (AFP) with a linear relationship in concentrations ranging from 0.1 ng mL-1 to 5 µg mL-1 and a low limit of detection of 42 pg mL-1. Our method was successfully confirmed for the detection of AFP in real serum samples from hepatocellular carcinoma (HCC) patients, demonstrating the great potential for clinical diagnosis.

2.
Biochem Biophys Res Commun ; 540: 83-89, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33450484

RESUMO

Intracrine androgen synthesis plays a critical role in the development of castration-resistant prostate cancer (CRPC). Aldo-keto reductase family 1 member C3 (AKR1C3) is a vital enzyme in the intracrine androgen synthesis pathway. In this study, mesoporous silica nanoparticles (MSNs) were employed to deliver small interfering RNA targeting AKR1C3 (siAKR1C3) to downregulate AKR1C3 expression in CPRC cells. The optimal weight ratio of MSNs/siAKR1C3 was determined by a gel retardation assay. Prostate cancer cells such as VCaP cells, which intracrinally express AKR1C3, and LNCaP-AKR1C3 cells stably transfected with AKR1C3 were used to investigate the antitumour effect of MSNs-siAKR1C3. Fluorescence detection and Western blot analyses were applied to confirm the entrance of MSNs-siAKR1C3 into the cells. A SRB (Sulforhodamine B) assay was employed to assess the cell viability, and a radioimmunoassay was used to measure the androgen concentration. Moreover, real-time PCR (RT-PCR), Western blot analysis and ELISA were used to determine the transcription and expression of prostate-specific antigen (PSA), AKR1C3 and androgen receptor (AR). Meanwhile, a reporter gene assay was performed to determine the AR activity. Additionally, a castrated nude mouse xenograft tumour model was produced to verify the inhibitory effect of MSNs-siAKR1C3 in vivo. The results showed that the optimal weight ratio of MSNs/siAKR1C3 was 140:1, and the complex could effectively enter cells, downregulate AKR1C3 expression, reduce the androgen concentration, inhibit AR activation, and inhibit CRPC development both in vitro and in vivo. These results indicate that decreasing intracrine androgen synthesis and inactivating AR signals by MSNs-siAKR1C3 may be a potential effective method for CRPC treatment.

3.
Ther Adv Med Oncol ; 12: 1758835920971421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240401

RESUMO

Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.

4.
Front Oncol ; 10: 579464, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072611

RESUMO

Malignant pleural mesothelioma (MPM) is the epitome of a recalcitrant cancer driven by pharmacologically intractable tumor suppressor proteins. A significant but largely unmet challenge in the field is the translation of genetic information on alterations in tumor suppressor genes (TSGs) into effective cancer-specific therapies. The notion that abnormal tumor genome subverts physiological cellular processes, which creates collateral vulnerabilities contextually related to specific genetic alterations, offers a promising strategy to target TSG-driven MPM. Moreover, emerging evidence has increasingly appreciated the therapeutic potential of genetic and pharmacological dependencies acquired en route to cancer development and drug resistance. Here, we review the most recent progress on vulnerabilities co-selected by functional loss of major TSGs and dependencies evolving out of cancer development and resistance to cisplatin based chemotherapy, the only first-line regimen approved by the US Food and Drug Administration (FDA). Finally, we highlight CRISPR-based functional genomics that has emerged as a powerful platform for cancer drug discovery in MPM. The repertoire of MPM-specific "Achilles heel" rises on the horizon, which holds the promise to elucidate therapeutic landscape and may promote precision oncology for MPM.

5.
Nat Commun ; 11(1): 5215, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060606

RESUMO

The sluggish electrochemical kinetics of sulfur species has impeded the wide adoption of lithium-sulfur battery, which is one of the most promising candidates for next-generation energy storage system. Here, we present the electronic and geometric structures of all possible sulfur species and construct an electronic energy diagram to unveil their reaction pathways in batteries, as well as the molecular origin of their sluggish kinetics. By decoupling the contradictory requirements of accelerating charging and discharging processes, we select two pseudocapacitive oxides as electron-ion source and drain to enable the efficient transport of electron/Li+ to and from sulfur intermediates respectively. After incorporating dual oxides, the electrochemical kinetics of sulfur cathode is significantly accelerated. This strategy, which couples a fast-electrochemical reaction with a spontaneous chemical reaction to bypass a slow-electrochemical reaction pathway, offers a solution to accelerate an electrochemical reaction, providing new perspectives for the development of high-energy battery systems.

6.
Phys Chem Chem Phys ; 22(33): 18703-18710, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32803209

RESUMO

Efficient production of cyclic polymers has been a hot topic in the past few decades. In this work, we found that an adsorptive porous template with an appropriate size has the capability to accelerate the ring closure of a linear polymer chain in a dilute solution with a higher yield. The restricted pore provides a confined space and the effect of its characteristics, such as pore size, shape and adsorption strength on cyclization time, is systematically studied by using dissipative particle dynamics simulations. As a prerequisite of cyclization in confinement, the entry process of linear precursors has been studied as well. Total production time is governed by a tradeoff between the size effect caused by decreasing the size of the pore and the adsorption of the pore. The strong size effect suppresses polymer entry but accelerates cyclization. The stronger adsorption promotes polymer entry but decelerates cyclization. According to our defined total production time, a small spherical confinement with strong adsorption results in a shorter total production time of cyclic polymers compared to that in free solution. If chain cyclization is permitted during its entering the confinement, the interplay between steric hindrance caused by pore size and adsorption provides an additional 'virtual' confinement at the boundary between confinement and free solution. In this case, an optimal cyclization time is observed with an appropriate adsorption strength under small confinement. Our results provide useful guidance for designing suitable porous templates for producing cyclic polymers with high efficiency.

7.
Cancers (Basel) ; 12(8)2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32824422

RESUMO

Background: Malignant pleural mesothelioma (MPM) is driven by the inactivation of tumor suppressor genes (TSGs). An unmet need in the field is the translation of the genomic landscape into effective TSG-specific therapies. Methods: We correlated genomes against transcriptomes of patients' MPM tumors, by weighted gene co-expression network analysis (WGCNA). The identified aberrant biochemical networks and potential drug targets induced by tumor suppressor loss were validated by integrative data analysis and functional interrogation. Results: CDKN2A/2B loss activates G2/M checkpoint and PI3K/AKT, prioritizing a co-targeting strategy for CDKN2A/2B-null MPM. CDKN2A deficiency significantly co-occurs with deletions of anti-viral type I interferon (IFN-I) genes and BAP1 mutations, that enriches the IFN-I signature, stratifying a unique subset, with deficient IFN-I, but proficient BAP1 for oncolytic viral immunotherapies. Aberrant p53 attenuates differentiation and SETD2 loss acquires the dependency on EGFRs, highlighting the potential of differentiation therapy and pan-EGFR inhibitors for these subpopulations, respectively. LATS2 deficiency is linked with dysregulated immunoregulation, suggesting a rationale for immune checkpoint blockade. Finally, multiple lines of evidence support Dasatinib as a promising therapeutic for LATS2-mutant MPM. Conclusions: Systematic identification of abnormal cellular processes and potential drug vulnerabilities specified by TSG alterations provide a framework for precision oncology in MPM.

8.
Heliyon ; 6(6): e04243, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32613119

RESUMO

Un-differentiated (UD) and well-differentiated (WD) normal human primary bronchial/tracheal epithelial cells are important respiratory cell models. Mature, WD cells which can be derived by culturing UD cells at an air-liquid interface represent a good surrogate for in vivo human airway epithelium. The overall protein profile of WD cells is poorly understood; therefore, the current study evaluated the proteomic characteristics of WD and UD cells using label-free LC-MS/MS and LC-PRM/MS. A total of 3,579 proteins were identified in WD and UD cells. Of these, 198 proteins were identified as differentially expressed, with 121 proteins upregulated and 77 proteins downregulated in WD cells compared with UD cells. Differentially expressed proteins were mostly enriched in categories related to epithelial structure formation, cell cycle, and immunity. Fifteen KEGG pathways and protein interaction networks were enriched and identified. The current study provides a global protein profile of WD cells, and contributes to understanding the function of human airway epithelium.

9.
Chem Biol Drug Des ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32603003

RESUMO

The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy)ethyl)-5-[125/131 I]iodo-1,2,3-triazole-diestradiol ([125/131 I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [125/131 I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [125/131 I]ITE2 had good stability in vitro and moderate molar activity (0.3 ± 0.2 GBq/µmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [131 I]ITE2 had high uptake in ER-abundant uterine and ovarian (5.7 ± 0.4 and 10.1 ± 1.4%ID/g at 1 hr postinjection) and could be blocked by co-injection of estradiol (2.7 ± 0.1 and 5.5 ± 0.4%ID/g) obviously. In the SPECT/CT imaging study, [125 I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1 ± 0.4%ID/g) than that of MDA-MB-231 (0.9 ± 0.1%ID/g). Furthermore, the specific uptake of [125 I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2 ± 0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis.

10.
Environ Sci Pollut Res Int ; 27(25): 31477-31488, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32483722

RESUMO

Submerged macrophytes and phytoplankton assemblage play significant roles in the functioning of aquatic ecosystems. An experiment was carried out in Beijing in order to further evaluate the environmental factors that affect the growth of submerged macrophytes and phytoplankton assemblage. Submerged macrophytes (i.e., Vallisneria natans, Hydrilla verticillata, and Ceratophyllum demersum) constructed the growth system with some controllable influencing factors (i.e., the flow rate and water depth gradient). The flow rates were set separately as 4 L/h (1#), 6 L/h (2#), and 12 L/h (3#), while the water depth gradient was of 0.5-1.7 m in eutrophic water. Generally, all macrophytes could grow normally in the experiment, and the system could maintain and improve the effluent quality. The average removal rates of NH3-N, COD, NO3-N, TN, and TP were about 90%, 33%, 65%, 45%, and 40%, respectively. Seen from the results of the water depth gradient experiments, it is indicated that Vallisneria natans grows better in shallow water (0.5 m) and moderate shallow water (0.7 m) area, with an average relative growth rate (ARGA) of 57%. Hydrilla verticillata and Ceratophyllum demersum grow better in moderate deep water (1.2 m) and deep water (1.7 m) area (ARGA of 66% and 64%, respectively). Results of the flow rate experiments showed that the moderate flow rate (6 L/h) was the best for those three macrophytes' growth. As the fitting results of the rapid light curves (RLCs) showed that the utilization of light and the tolerance to strong light were different for these macrophytes, if they are ranked in the order of the utilization and the tolerance from strong to weak, they are Hydrilla verticillata, Ceratophyllum demersum, and Vallisneria natans. Microbial analyses indicated that the overall system diversity of the experimental groups have been improved after cultivation of macrophytes. However, the accumulated Cyanobacteria caused by the low flow rate (1#) would lead to the suppression of microbial organics decomposition and nutrient metabolism in the macrophytes. To sum up, the results of this study provided theoretical guidance and technical support for the restoration of submerged macrophytes in eutrophic water.


Assuntos
Hydrocharitaceae , Fitoplâncton , Pequim , Biomassa , Ecossistema , Lagos , Fotossíntese , Água
11.
Nucl Med Biol ; 86-87: 44-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474281

RESUMO

OBJECTIVE: Accurate evaluation of tumor programmed death ligand 1 (PD-L1) expression can assist in predicting whether a patient will respond to anti-PD-L1 therapy. In this study, we aimed to develop stable radioiodinated PD-L1 antibodies that can be used for PD-L1 targeted SPECT/PET imaging. METHODS: Radioiodination was accomplished via a prosthetic group ([131I]SIB or [124I]SIB) to give radioiodinated anti-human PD-L1 and anti-mouse PD-L1 antibody (anti-PD-L1 and anti-PD-L1M). MicroSPECT/PET imaging and biodistribution of radioiodinated antibodies were studied in two immune-competent murine models (B16F10 and 4T1 syngeneic tumor models) and patient-derived xenograft (PDX) model of lung adenocarcinoma to evaluate the feasibility of identifying tumor PD-L1 expression. RESULTS: Radioiodinated PD-L1 antibodies had high radiochemical purity (>99%) and favorable stability in vivo. There was high uptake of [131I]SIB-anti-PD-L1M in both 4T1 and B16F10 syngeneic tumors when injected with 5.5 MBq radiotracers containing 200 µg anti-mouse-PD-L1. The presence of excess unlabeled anti-PD-L1 antibody increased [131I]SIB-anti-PD-L1M uptake in tumors. The highly specific PD-L1-positive tumor uptake detected by SPECT imaging indicated that radioiodinated antibody could be used for PD-L1 expression imaging. In addition, PET imaging of the PDX model was performed with [124I]SIB-anti-PD-L1, which showed high signal intensity in tumors and optimal contrast between tumor and muscle (tumor-to-muscle ratios at 6 h p.i. and 24 h p.i. were 2.5 and 5.3, respectively). CONCLUSIONS: This study provides an efficient strategy for synthesizing stable radioiodinated PD-L1 antibodies with excellent pharmacokinetics to identify PD-L1 expression in tumors.

13.
ACS Sens ; 5(7): 2184-2190, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32571009

RESUMO

Current strategies for the detection of disease biomarkers often require enzymatic assays that may have limited sensitivity due to inferior stability and vulnerable catalytic activity of the enzyme. A new enzyme-free amplification method for identifying suitable biomarkers is necessary to lower the limit of detection and improve many critical diagnosis applications. Here, we presented an enzyme-free amplified plasmonic immunoassay that enhanced the detection sensitivity of disease biomarkers by combining a novel plasmon-induced silver photoreduction system with a silver nanoparticle (AgNP)-linked immunoassay. The key step to achieving ultrasensitivity was to use Ag+ from dissolved AgNPs that control the growth rate of the silver coating on plasmonic nanosensors under visible light illumination. We demonstrated the outstanding sensitivity and robustness of this assay by detecting the disease biomarker alpha-fetoprotein (AFP) at a low concentration of 3.3 fg mL-1. The detection of AFP was further confirmed in the sera of hepatocellular carcinoma patients.

14.
Front Immunol ; 11: 911, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536915

RESUMO

Hemocytes play unequivocally central roles in host immune defense of bivalve mollusks, though the exact mechanisms underlying their functional differentiation are only partially understood. To this end, granulocytes and hyalinocytes were sorted via flow cytometry from hemocytes of the Pacific oyster Crassostrea gigas, and consequently quantitative transcriptomic analysis revealed a striking array of differentially expressed genes (DEGs), which were globally upregulated in granulocytes, dedicating to functional differentiation among oyster hemocytes. Our network of DEGs illustrated actively engaged signaling pathways, with Cdc42/Cdc42l being a core regulator of pathway network, which was validated by a dramatically reduced capacity for hemocyte phagocytosis in the presence of Cdc42 inhibitors. Additionally, a number of transcription factors were identified among DEGs, including ELK, HELT, and Fos, which were predominantly expressed in granulocytes. The AP-1 transcription factor Fos was confirmed to facilitate functional differentiation of hemocytes in an assay on binding to target genes by the AP-1 binding site, consistent with downstream phagocytosis and ROS production. Importantly, Cdc42/Cdc42l were also regulated by the expression of Fos, providing a possible regulatory mechanism-guided hemocyte functional differentiation. Findings in this study have bridged a knowledge gap on the mechanistic underpinnings of functional differentiation of hemocytes in a marine invertebrate C. gigas, which promise to facilitate research on the evolution of immune defense and functional differentiation of phagocyte in higher-order and more recent phyla.

15.
Proc Natl Acad Sci U S A ; 117(21): 11233-11239, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32393637

RESUMO

Pulsating flows through tubular geometries are laminar provided that velocities are moderate. This in particular is also believed to apply to cardiovascular flows where inertial forces are typically too low to sustain turbulence. On the other hand, flow instabilities and fluctuating shear stresses are held responsible for a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates. Geometrical distortions of small, yet finite, amplitude are found to excite a state consisting of helical vortices during flow deceleration. The resulting flow pattern grows rapidly in magnitude, breaks down into turbulence, and eventually returns to laminar when the flow accelerates. This scenario causes shear stress fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions can adversely affect blood vessels and have been shown to promote inflammation and dysfunction of the shear stress-sensitive endothelial cell layer.

16.
Nanoscale ; 12(21): 11364-11394, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32428057

RESUMO

Two-dimensional (2D) materials have been the focus of materials research for many years due to their unique fascinating properties and large specific surface area (SSA). They are very sensitive to the analytes (ions, glucose, DNA, protein, etc.), resulting in their wide-spread development in the field of sensing. New 2D materials, as the basis of applications, are constantly being fabricated and comprehensively studied. In a variety of sensing applications, the solution-gated transistor (SGT) is a promising biochemical sensing platform because it can work at low voltage in different electrolytes, which is ideal for monitoring body fluids in wearable electronics, e-skin, or implantable devices. However, there are still some key challenges, such as device stability and reproducibility, that must be faced in order to pave the way for the development of cost-effective, flexible, and transparent SGTs with 2D materials. In this review, the device preparation, device physics, and the latest application prospects of 2D materials-based SGTs are systematically presented. Besides, a bold perspective is also provided for the future development of these devices.

18.
Sci Rep ; 10(1): 6577, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313134

RESUMO

Phagosomes are task-force organelles of innate immune systems, and evolutionary diversity and continuity abound in the protein machinery executing this coordinately regulated process. In order to clarify molecular mechanisms underlying phagocytosis, we studied phagocyte response to beads and Vibrio species, using hemocytes of the Pacific oysters (Crassostrea gigas) as a marine invertebrate model. Phagosomes from different stages of phagocytosis were isolated by density-gradient centrifugation, and more than 400 phagosome-associated proteins were subsequently identified via high-throughput quantitative proteomics. In modeling key networks of phagosomal proteins, our results support the essential roles of several processes driving phagosome formation and maturation, including cytoskeleton remodeling and signal transduction by Rab proteins. Several endoplasmic reticulum (ER)-associated proteins were identified, while live cell imaging confirms an apparent intimate interaction between the ER and phagosomes. In further quantitative proteomic analysis, the signal transducers CgRhoGDI and CgPI4K were implicated. Through experimental validation, CgRhoGDI was shown to negatively regulate actin cytoskeleton remodeling in the formation of oyster phagosomes, while CgPI4K signaling drives phagosome maturation and bacterial killing. Our current work illustrates the diversity and dynamic interplay of phagosomal proteins, providing a framework for better understanding host-microbe interactions during phagosome activities in under-examined invertebrate species.


Assuntos
Citoesqueleto/genética , Hemócitos/metabolismo , Fagocitose/genética , Proteoma/genética , Animais , Organismos Aquáticos/genética , Organismos Aquáticos/metabolismo , Crassostrea/genética , Crassostrea/metabolismo , Citoesqueleto/metabolismo , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Fagossomos/metabolismo
19.
PLoS Genet ; 16(4): e1008663, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243438

RESUMO

Previous studies have surveyed the potential impact of loss-of-function (LoF) variants and identified LoF-tolerant protein-coding genes. However, the tolerance of human genomes to losing enhancers has not yet been evaluated. Here we present the catalog of LoF-tolerant enhancers using structural variants from whole-genome sequences. Using a conservative approach, we estimate that individual human genomes possess at least 28 LoF-tolerant enhancers on average. We assessed the properties of LoF-tolerant enhancers in a unified regulatory network constructed by integrating tissue-specific enhancers and gene-gene interactions. We find that LoF-tolerant enhancers tend to be more tissue-specific and regulate fewer and more dispensable genes relative to other enhancers. They are enriched in immune-related cells while enhancers with low LoF-tolerance are enriched in kidney and brain/neuronal stem cells. We developed a supervised learning approach to predict the LoF-tolerance of all enhancers, which achieved an area under the receiver operating characteristics curve (AUROC) of 98%. We predict 3,519 more enhancers would be likely tolerant to LoF and 129 enhancers that would have low LoF-tolerance. Our predictions are supported by a known set of disease enhancers and novel deletions from PacBio sequencing. The LoF-tolerance scores provided here will serve as an important reference for disease studies.


Assuntos
Elementos Facilitadores Genéticos/genética , Genoma Humano/genética , Mutação com Perda de Função , Sequência Conservada , Doença/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Especificidade de Órgãos/genética , Curva ROC , Reprodutibilidade dos Testes , Aprendizado de Máquina Supervisionado
20.
PLoS One ; 15(4): e0231399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32276269

RESUMO

Vibrio coralliilyticus is a pathogen of coral and mollusk, contributing to dramatic losses worldwide. In our study, we found that V. coralliilyticus challenge could directly affect adult Tridacna crocea survival; there were dead individuals appearing at 6 h post infection, and there were 45.56% and 56.78% mortality rates in challenged groups after 36 h of infection. The apoptosis rate of hemocytes was significantly increased by 1.8-fold at 6 h after V. coralliilyticus injection. To shed light on the mechanistic molecular responses of T. crocea to V. coralliilyticus infection, we used transcriptome sequencing analysis and other relevant techniques to analyze T. crocea hemocytes at 0 h, 6 h, 12 h and 24 h after V. coralliilyticus challenge. Our results revealed that the total numbers of unigenes and DEGs were 195651 and 3446, respectively. Additional details were found by KEGG pathway enrichment analysis, where DEGs were significantly enriched in immune-related signaling pathways, such as the TLR signaling pathway, and some were associated with signaling related to apoptosis. Quantitative validation results illustrated that with exposure to V. coralliilyticus, the expression of TLR pathway members, TLR, MyD88, IRAK4, TRAF6, and IкB-α, were significantly upregulated (by 22.9-, 9.6-, 4.0-, 3.6-, and 3.9-fold, respectively) at 6 h. The cytokine-related gene IL-17 exhibited an increase of 6.3-fold and 10.5-fold at 3 h and 6 h, respectively. The apoptosis-related gene IAP1 was dramatically increased by 2.99-fold at 6 h. These results indicate that adult T. crocea could initiate the TLR pathway to resist V. coralliilyticus, which promotes the release of inflammatory factors such as IL-17 and leads to the activation of a series of outcomes, such as apoptosis. The response mechanism is related to the T. crocea immunoreaction stimulated by V. coralliilyticus, providing a theoretical basis for understanding T. crocea immune response mechanisms.


Assuntos
Bivalves/imunologia , Transcriptoma , Vibrio/patogenicidade , Animais , Bivalves/genética , Bivalves/microbiologia , Citocinas/genética , Citocinas/metabolismo , Hemócitos/metabolismo , Hemócitos/microbiologia , Imunidade Inata , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
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