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2.
Imeta ; 3(2): e181, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882496

RESUMO

Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

3.
Front Chem ; 12: 1416059, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828017

RESUMO

The cathode in lithium-selenium (Li-Se) batteries has garnered extensive attention owing to its superior specific capacity and enhanced conductivity compared to sulfur. Nonetheless, the adoption and advancement of Li-Se batteries face significant challenges due to selenium's low reactivity, substantial volume fluctuations, and the shuttle effect associated with polyselenides. Single-atom catalysts (SACs) are under the spotlight for their outstanding catalytic efficiency and optimal atomic utilization. To address the challenges of selenium's low chemical activity and volume expansion in Li-Se batteries, through electrospun, we have developed a lotus root-inspired carbon nanofiber (CNF) material, featured internal multi-channels and anchored with molybdenum (Mo) single atoms (Mo@CNFs). Mo single atoms significantly enhance the conversion kinetics of selenium (Se), facilitating rapid formation of Li2Se. The internally structured multi-channel CNF serves as an effective host matrix for Se, mitigating its volume expansion during the electrochemical process. The resulting cathode, Se/Mo@CNF composite, exhibits a high discharge specific capacity, superior rate performance, and impressive cycle stability in Li-Se batteries. After 500 cycles at a current density of 1 C, it maintains a capacity retention rate of 82% and nearly 100% coulombic efficiency (CE). This research offers a new avenue for the application of single-atom materials in enhancing advanced Li-Se battery performance.

4.
Mater Horiz ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864466

RESUMO

Nanosprings demonstrate promising mechanical characteristics, positioning them as pivotal components in a diverse array of potential nanoengineering applications. To unlock the full potential of these nanosprings, ongoing research is concentrated on emulating springs at the nanoscale in terms of both morphology and function. This review underscores recent advancements in the field and provides a comprehensive overview of the diverse methods employed for nanospring preparation. Understanding the general mechanism behind nanospring formation lays the groundwork for the informed design of nanosprings. The synthesis section delineates four prominent methods employed for nanospring fabrication: vapor phase synthesis, templating methods, post-treatment techniques, and molecular engineering. Each method is critically analyzed, highlighting its strengths, limitations, and potential for scalability. Mechanical properties of nanosprings are explored in depth, discussing their response to external stimuli and their potential applications in various fields such as sensing, energy storage, and biomedical engineering. The interplay between nanospring morphology and mechanical behavior is elucidated, providing insights into the design principles for tailored functionality. Additionally, we anticipate that the evolution of state-of-the-art characterization tools, such as in situ transmission electron microscopy, 3D electron tomography, and machine learning, will significantly contribute to both the study of nanospring mechanisms and their applications.

5.
Cell Rep ; 43(6): 114324, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38850536

RESUMO

Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo ß-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.


Assuntos
Hepatócitos , Piroptose , Sepse , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Hepatócitos/metabolismo , Hepatócitos/imunologia , Sepse/imunologia , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Lipopolissacarídeos , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Mitofagia , Lectinas Tipo C/metabolismo , Imunidade Inata , Histonas/metabolismo , beta-Glucanas/farmacologia , Imunidade Treinada
6.
Waste Manag ; 183: 209-219, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38761485

RESUMO

Lithium iron phosphate batteries, known for their durability, safety, and cost-efficiency, have become essential in new energy applications. However, their widespread use has highlighted the urgency of battery recycling. Inadequate management could lead to resource waste and environmental harm. Traditional recycling methods, like hydrometallurgy and pyrometallurgy, are complex and energy-intensive, resulting in high costs. To address these challenges, this study introduces a novel low-temperature liquid-phase method for regenerating lithium iron phosphate positive electrode materials. By using N2H4·H2O as a reducing agent, missing Li+ ions are replenished, and anti-site defects are reduced through annealing. This process restores nearly all missing Li+ ions at 80 °C/6h. After high-temperature sintering at 700 °C/2h, the regenerated LiFePO4 matches commercial LiFePO4 in terms of anti-site defects and exhibits excellent performance with a 97 % capacity retention rate after 100 cycles at 1C. Compared to high-temperature techniques, this low-temperature liquid-phase method is simpler, safer, and more energy-efficient, offering a blueprint for reclaiming discarded LiFePO4 and similar materials.


Assuntos
Fontes de Energia Elétrica , Lítio , Fosfatos , Reciclagem , Reciclagem/métodos , Lítio/química , Fosfatos/química , Temperatura , Eletrodos , Compostos Férricos , Ferro
7.
Sci Rep ; 14(1): 10903, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740773

RESUMO

Assembly construction is extensively employed in bridge construction due to its ability to accelerate construction and improve quality. To speed the recovery of bridges after major earthquakes, this study proposes an assembled connection for precast piers and footings based on assembly construction. The precast piers are connected to the footings using ultra-high-performance concrete (UHPC) post-cast cupped sockets. Two specimens are tested with a 1:4 scale, namely, the cast-in-place (CIP) specimen and, the UHPC cupped socket pier specimen. Finite element models (FEM) of a continuous girder bridge with cupped socket connections are developed and verified by experimental results. The seismic fragility analysis is conducted to investigate the difference between the cupped socket connection and the CIP connection. The experimental results showed that the plastic hinge was formed on the precast piers and there was little damage to the UHPC sockets. The results of FEA indicate that UHPC cupped socket piers have slightly higher seismic fragility than the seismic fragility of cast-in-place piers. Then, some methods were proposed to reduce the seismic fragility of UHPC cupped socket piers, and their availability was confirmed by comparing them with the seismic fragility of CIP piers. Finally, an example bridge with this connection is introduced to illustrate replacing prefabricated piers after an earthquake.

8.
Nanoscale ; 16(6): 2945-2954, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38236129

RESUMO

In various domains spanning materials synthesis, chemical catalysis, life sciences, and energy materials, in situ transmission electron microscopy (TEM) methods exert a profound influence. These methodologies enable the real-time observation and manipulation of gas-phase and liquid-phase reactions at the nanoscale, facilitating the exploration of pivotal reaction mechanisms. Fundamental research areas like crystal nucleation, growth, etching, and self-assembly have greatly benefited from these techniques. Additionally, their applications extend across diverse fields such as catalysis, batteries, bioimaging, and drug delivery kinetics. However, the intricate nature of 'soft matter' presents a challenge due to the unique molecular properties and dynamic behavior of these substances that remain insufficiently understood. Investigating soft matter within in situ liquid-phase TEM settings demands further exploration and advancement compared to other research domains. This research harnesses the potential of in situ liquid-phase TEM technology while integrating deep learning methodologies to comprehensively analyze the quantitative aspects of soft matter dynamics. This study centers on diverse phenomena, encompassing surfactant molecule nucleation, block copolymer behavior, confinement-driven self-assembly, and drying processes. Furthermore, deep learning techniques are employed to precisely analyze Ostwald ripening and digestive ripening dynamics. The outcomes of this study not only deepen the understanding of soft matter at its fundamental level but also serve as a pivotal foundation for developing innovative functional materials and cutting-edge devices.

9.
Fish Shellfish Immunol ; 144: 109285, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092095

RESUMO

Poly(I:C) is known as an agonist of the TLR3 receptor which could prime inflammation and elicit the host immune response, which is widely applied as adjuvant or antivirus treatment. However, the negative effects of poly(I:C) on regulating immune response to protect the host from inflammatory diseases remain largely unknown. Here, we establish an in vivo model to pre-treat zebrafish larvae with poly(I:C) at 2 dpf, then challenge them with LPS at 6 dpf, and find that poly(I:C) training could significantly alleviate the LPS challenge-induced septic shock and inflammatory phenotypes. Moreover, the poly(I:C)-trained larvae exhibit decreased number of macrophages, but not neutrophils, after secondary LPS challenge. Furthermore, training the larvae with poly(I:C) could elevate the transcripts of mTOR signaling and heighten the H3K4me3-mediated epigenetic modifications. And interestingly, we find that inhibiting the H3K4me3 modification, rather than mTOR signaling, could recover the number of macrophages in poly(I:C)-trained larvae, which is consistent with the observations of inflammatory phenotypes. Taken together, these results suggest that poly(I:C) training could induce epigenetic rewiring to mediate the anti-inflammatory response against secondary LPS challenge-induced septic shock through decreasing macrophages' number in vivo, which might expand our understanding of poly(I:C) in regulating fish immune response.


Assuntos
Lipopolissacarídeos , Choque Séptico , Animais , Lipopolissacarídeos/efeitos adversos , Peixe-Zebra , Larva , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Serina-Treonina Quinases TOR
10.
Opt Express ; 31(20): 33113-33122, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859098

RESUMO

Recently, the diffractive deep neural network (D2NN) has demonstrated the advantages to achieve large-scale computational tasks in terms of high speed, low power consumption, parallelism, and scalability. A typical D2NN with cascaded diffractive elements is designed for monochromatic illumination. Here, we propose a framework to achieve the multi-wavelength D2NN (MW-D2NN) based on the method of weight coefficients. In training, each wavelength is assigned a specific weighting and their output planes construct the wavelength weighting loss function. The trained MW-D2NN can implement the classification of images of handwritten digits at multi-wavelength incident beams. The designed 3-layers MW-D2NN achieves a simulation classification accuracy of 83.3%. We designed a 1-layer MW-D2NN. The simulation and experiment classification accuracy are 71.4% and 67.5% at RGB wavelengths. Furthermore, the proposed MW-D2NN can be extended to intelligent machine vision systems for multi-wavelength and incoherent illumination.

11.
J Immunol ; 211(11): 1693-1700, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37843506

RESUMO

B lymphocytes engaged in humoral immunity play a critical role in combating pathogenic infections; however, the mechanisms of NK cells in regulating the responses of B cells remain largely unknown. In the present study, we established an Edwardsiella piscicida infection model in turbot (Scophthalmus maximus) and found that the production of IgM was decreased. Meanwhile, through establishing the head kidney-derived lymphocyte infection model, we revealed that the impairment of IgMhi B cells was associated with bacterial infection-induced perforin production. Interestingly, we reveal that perforin production in NK cells is tightly regulated by an inhibitory novel immune-type receptor, NITR12. Moreover, we confirm that inhibiting NITR12 can result in elevated perforin production, engaging the impairment of IgMhi B cells. Taken together, these findings demonstrate an innovative strategy of NK cells in mediating B lymphocyte killing in turbot and suggest that relieving NK cells through NITR12 might be the target for the development of efficacious vaccines.


Assuntos
Doenças dos Peixes , Linguados , Animais , Perforina , Células Matadoras Naturais , Linfócitos B , Morte Celular
12.
Dev Comp Immunol ; 149: 104904, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37543221

RESUMO

Pyroptosis, an inflammatory form of programmed cell death, is directly executed by gasdermin (GSDM) depending on its N-terminal pore-forming fragment-mediated membrane-disrupting, triggering intracellular contents release, which plays important roles in mammalian anti-infection and anti-tumor immune responses. However, whether pyroptosis engages in the regulation of tissue regeneration remains largely unknown. Here, utilizing Hydra vulgaris as the research model, we found that an HyCARD2-HyGSDME-mediated pyroptosis signalling is activated in both head and foot regenerated tips after amputation. Impeding pyroptosis by knocking down the expression of either HyGSDME or HyCARD2 significantly hampered both head and foot regeneration in Hydra. Mechanistically, the activation of HyCARD2-HyGSDME axis at wound sites is dependent of intracellular mitochondrial reactive oxygen species (mtROS), the removing of which hindered Hydra head regeneration. Moreover, the HyCARD2-HyGSDME axis-gated pyroptosis was found to enhance the initial secretion and upregulated expression of Wnt3. Collectively, these findings indicate that gasdermin-gated pyroptosis is critical for the evoking of Wnt signalling to facilitate Hydra tissue regeneration, which provides insights into functional diversification within the gasdermin family in the animal kingdom.


Assuntos
Hydra , Piroptose , Animais , Hydra/metabolismo , Gasderminas , Apoptose , Via de Sinalização Wnt , Inflamassomos/metabolismo , Mamíferos
13.
Fish Shellfish Immunol ; 141: 109005, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37604262

RESUMO

T-helper 17 lymphocytes (Th17) are the most common inflammatory cells identified in mammals. However, the identification of Th17 cells and the clarification of their function in teleost fish remain largely unknown. In this study, we took advantage of the single-cell RNA sequencing-based immune cell atlas that was identified in turbot (Scophthalmus maximus), and revealed two chemokine-related genes, ccl20a.3 and ccl20l, that were specifically expressed in Th17 cells. Moreover, through immuno-fluorescence analysis, we found that CCL20a.3 or CCL20l was co-expressed with the classical makers in Th17 cells, including IL17a/f1 and IL22. Furthermore, through a Th17 lineage-specific transcription factor RORc inhibitor GSK805 treatment, we found that the expression of ccl20a.3 and ccl20l was significantly impaired, compared with other T cell markers. Besides, we also found that ccl20a.3 and ccl20l exhibited the same dynamic response with the classical markers that were identified in Th17 cells during bacterial infection. Taken together, these results provide potential gene markers for better understanding of the dynamic immune responses of Th17 cells in teleost fish.

14.
Nanoscale ; 15(33): 13718-13727, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37577754

RESUMO

In situ liquid phase transmission electron microscopy (TEM) and three-dimensional electron tomography are powerful tools for investigating the growth mechanism of MOFs and understanding the factors that influence their particle morphology. However, their combined application to the study of MOF etching dynamics is limited due to the challenges of the technique such as sample preparation, limited field of view, low electron density, and data analysis complexity. In this research, we present a study employing in situ liquid phase TEM to investigate the etching mechanism of colloidal zeolitic imidazolate framework (ZIF) nanoparticles. The etching process involves two distinct stages, resulting in the development of porous structures as well as partially and fully hollow morphologies. The etching process is induced by exposure to an acid solution, and both in situ and ex situ experiments demonstrate that the outer layer etches faster leading to overall volume shrinking (stage I) while the inner layer etches faster giving a hollow morphology (stage II), although both the outer layer and inner layer have been etched in the whole process. 3D electron tomography was used to quantify the properties of the hollow structures which show that the ZIF-67 crystal etching rate is larger than that of the ZIF-8 crystal at the same pH value. This study provides valuable insights into MOF particle morphology control and can lead to the development of novel MOF-based materials with tailored properties for various applications.

15.
Sci Adv ; 9(29): eadh4054, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478191

RESUMO

Inflammatory caspases sensing lipopolysaccharide (LPS) to drive gasdermin (GSDM)-mediated pyroptosis is an important immune response mechanism for anti-infection defense in mammals. In this work, we resolved an LPS-induced and GSDM-gated pyroptosis signaling cascade in Cnidarians. Initially, we identified a functional GSDM protein, HyGSDME, in Hydra, executing cytosolic LPS-induced pyroptosis in a caspase-dependent manner. Further, we identified a proinflammatory caspase, HyCaspA, capable of sensing cytosolic LPS by an uncharacterized N-terminal domain relying on its unique hydrophobic property, thereby triggering its oligomerization and self-activation. Subsequently, the LPS-activated HyCaspA cleaved an apoptotic caspase, HyCARD2, to trigger HyGSDME-gated pyroptosis. Last, HyGSDME exhibited an enriched distribution on the ectodermal layer of Hydra polyps, exerting a canonical immune defense function against surface-invading bacteria. Collectively, our work resolved an ancient pyroptosis signaling cascade in Hydra, suggesting that inflammatory caspases sensing cytosolic LPS to initiate GSDM-gated pyroptosis are a conserved immune defense mechanism from Cnidarians to mammals.


Assuntos
Caspases , Hydra , Piroptose , Caspases/metabolismo , Hydra/fisiologia , Lipopolissacarídeos , Gasderminas , Transdução de Sinais
16.
J Appl Microbiol ; 134(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37500265

RESUMO

AIMS: Pseudomonas plecoglossicida (P. plecoglossicida) is the causative agent of visceral granulomas disease in large yellow croaker (Larimichthys crocea) and it causes severe economic loss to its industry. Biofilm formation, related to intracellular cyclic bis (3'-5') diguanylic acid (c-di-GMP) levels, is essential for the lifestyle of P. plecoglossicida. This research aims to investigate the role of YfiR-a key regulator of the diguanylate cyclase YfiN to regulate c-di-GMP levels and reveal its regulatory function of bacterial virulence expression in P. plecoglossicida. METHODS AND RESULTS: A genetic analysis was carried out to identify the yfiBNR operon for c-di-GMP regulation in P. plecoglossicida. Then, we constructed a yfiR mutant and observed increased c-di-GMP levels, enhanced biofilm formation, increased exopolysaccharides, and diminished swimming and swarming motility in this strain. Moreover, through establishing a yolk sac microinjection infection model in zebrafish larvae, an attenuated phenotype of yfiR mutant that manifested as restored survival and lower bacterial colonization was found. CONCLUSIONS: YfiR is the key regulator of virulence in P. plecoglossicida, which contributes to c-di-GMP level, biofilm formation, exopolysaccharides production, swimming, swarming motility, and bacterial colonization in zebrafish model.


Assuntos
Proteínas de Bactérias , Peixe-Zebra , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peixe-Zebra/metabolismo , Virulência , GMP Cíclico/genética , GMP Cíclico/metabolismo , Fenótipo , Regulação Bacteriana da Expressão Gênica , Biofilmes
17.
ACS Appl Mater Interfaces ; 15(17): 20583-20602, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37087764

RESUMO

Si-based rechargeable lithium-ion batteries (LIBs) have generated interest as silicon has remarkably high theoretical specific capacity. It is projected that LIBs will meet the increasing need for extensive energy storage systems, electric vehicles, and portable electronics with high energy densities. However, the Si-based LIB has a substantial problem due to the volume cycle variations brought on by Si, which result in severe capacity loss. Making Si-based anodes-enabled high-performance LIBs that are easy to utilize requires an understanding of the fading mechanism. Due to its distinct advantage in morphological changes from microscale to nanoscale, even approaching atomic resolution, electron microscopy is one of the most popular methods. Based on operando electron microscopy characterization, the general comprehension of the fading mechanism and the morphology evolution of Si-based LIBs are debated in this review. The current advancements in compositional and structural interpretation for Si-based LIBs using advanced electron microscopy characterization methods are outlined. The future development trends in pertinent silicon materials characterization methods are also highlighted, along with numerous potential research avenues for Si-based LIBs design and characterization.

18.
Fish Shellfish Immunol ; 136: 108746, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37054766

RESUMO

Bacterial disease is one of the important factors leading to economic losses in the turbot (Scophthalmus maximus) cultivation industry. T lymphocytes are major components of cellular immunity, whereas B lymphocytes produce immunoglobulins (Ig) that are key elements of humoral immune responses against infection. However, the genomic organization of genes encoding T-cell receptors (TCR) and immunoglobulin heavy chains (IgHs) in turbot remains largely unknown. In this study, abundant full-length transcripts of TCRs and IgHs were sequenced by Isoform-sequencing (Iso-seq), and we investigated and annotated the V, D, J and C gene loci of TCRα, TCRß, IgT, IgM and IgD in turbot. Furthermore, through single-cell RNA sequencing (scRNA-seq) of blood leukocytes, we confirmed that these identified TCRs and IgHs were highly expressed in T/B cell clusters, respectively. Meanwhile, we also identified the IgM+IgD+ B and IgT+ B cells with differential gene expression profiles and potential functions. Taken together, our results provide a comprehensive understanding of TCRs and IgHs loci in turbot, which will contribute to evolutionary and functional characterization of T and B lymphocytes in teleost.


Assuntos
Receptores de Antígenos de Linfócitos T , Linfócitos T , Animais , Receptores de Antígenos de Linfócitos T/genética , Cadeias Pesadas de Imunoglobulinas/genética , Evolução Biológica , Imunoglobulina M/genética , Imunoglobulina M/metabolismo
19.
Front Plant Sci ; 13: 991074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340390

RESUMO

Black shank disease caused by Phytophthora nicotianae is one of the most important diseases in tobacco worldwide and can result in a devastating loss in tobacco cultivation. Many efforts have been carried out to identify the chromosome segment from Nicotiana plumbaginifolia containing a resistance locus carrying a gene named Php; however, the Php gene has not been cloned, and knowledge of the potential mechanism of the Php gene in the resistant lines is limited. To further characterize the resistance mechanism of the Php gene, we first used the resistant line "RBST" and the susceptible cultivar "Honghuadajinyuan" (HD) to obtain the near-isogenic line RBS89 containing the Php gene from RBST. RBS89 showed high resistance to black shank disease. Transcriptomic and iTRAQ analyses were applied to explore the potential defense mechanisms in RBS89 plants in comparison with HD plants with or without inoculation. Many differentially expressed genes (DEGs) and proteins were identified, and some pathogenesis-related (PR) proteins were extensively abundant in the RBS89 plants when compared with the HD plants in response to black shank disease. Importantly, overexpression of the PR gene NtPR-1B in HD plants improved the resistance of tobacco plants to black shank disease, indicating that NtPR-1B and Php genes might have similar roles in protecting tobacco from black shank disease. However, the relationship between NtPR-1B and Php genes requires further analysis. Therefore, our study provides valuable information for breeding tobacco cultivars with black shank disease resistance and sheds light on the defense mechanism of black shank disease in tobacco for enhancing Phytophthora resistance in other Solanaceae crops.

20.
Front Pharmacol ; 13: 938391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910382

RESUMO

Background: Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD) worldwide, tubular injury is the driving force during the pathogenesis and progression of DN. Thus, we aim to utilize the connectivity map (CMap) with renal tubulointerstitial transcriptomic profiles of biopsy-proven DN to identify novel drugs for treating DN. Methods: We interrogated the CMap profile with tubulointerstitial transcriptomic data from renal biopsy-proven early- and late-stage DN patients to screen potential drugs for DN. Therapeutic effects of candidate drug were assessed in Murine model of diabetic kidney disease (STZ-induced CD-1 mice), and HK-2 cells and immortalized bone marrow-derived macrophages (iBMDMs). Results: We identified CAY10603, a specific inhibitor of histone deacetylase 6 (HDAC6), as a potential drug that could significantly reverse the altered genes in the tubulointerstitial component. In DN patients and mice, upregulation of HDAC6 was mainly observed in renal tubular cells and infiltrated macrophages surrounding the diluted tubules. In both early- and late-onset diabetic mice, daily CAY10603 administration effectively alleviated renal dysfunction and reduced macrophage infiltration, tubular injury and tubulointerstitial fibrosis. Mechanistically, CAY10603 suppressed NLRP3 activation in both HK-2 cells and iBMDMs. Conclusion: CAY10603 exhibited therapeutic potential for DN by suppressing NLRP3 inflammasome activation in both tubular cells and macrophages.

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