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With the flourishing of spatial omics technologies, alignment and stitching of slices becomes indispensable to decipher a holistic view of 3D molecular profile. However, existing alignment and stitching methods are unpractical to process large-scale and image-based spatial omics dataset due to extreme time consumption and unsatisfactory accuracy. Here we propose SANTO, a coarse-to-fine method targeting alignment and stitching tasks for spatial omics. SANTO firstly rapidly supplies reasonable spatial positions of two slices and identifies the overlap region. Then, SANTO refines the positions of two slices by considering spatial and omics patterns. Comprehensive experiments demonstrate the superior performance of SANTO over existing methods. Specifically, SANTO stitches cross-platform slices for breast cancer samples, enabling integration of complementary features to synergistically explore tumor microenvironment. SANTO is then applied to 3D-to-3D spatiotemporal alignment to study development of mouse embryo. Furthermore, SANTO enables cross-modality alignment of spatial transcriptomic and epigenomic data to understand complementary interactions.
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Neoplasias de la Mama , Animales , Ratones , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Transcriptoma/genética , Microambiente Tumoral/genética , Epigenómica/métodos , Genómica/métodos , Algoritmos , Embrión de Mamíferos/metabolismo , Imagenología Tridimensional/métodosRESUMEN
Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured ß cells and mouse ß cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.
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Diferenciación Celular , Células Madre Pluripotentes , Humanos , Animales , Ratones , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citología , Células Secretoras de Somatostatina/metabolismo , Células Secretoras de Somatostatina/citología , Endodermo/citología , Endodermo/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Páncreas/citología , Páncreas/metabolismo , Somatostatina/metabolismo , Linaje de la Célula , Insulina/metabolismo , Secreción de InsulinaRESUMEN
MOTIVATION: Macrocyclic peptides hold great promise as therapeutics targeting intracellular proteins. This stems from their remarkable ability to bind flat protein surfaces with high affinity and specificity while potentially traversing the cell membrane. Research has already explored their use in developing inhibitors for intracellular proteins, such as KRAS, a well-known driver in various cancers. However, computational approaches for de novo macrocyclic peptide design remain largely unexplored. RESULTS: Here, we introduce HELM-GPT, a novel method that combines the strength of the hierarchical editing language for macromolecules (HELM) representation and generative pre-trained transformer (GPT) for de novo macrocyclic peptide design. Through reinforcement learning (RL), our experiments demonstrate that HELM-GPT has the ability to generate valid macrocyclic peptides and optimize their properties. Furthermore, we introduce a contrastive preference loss during the RL process, further enhanced the optimization performance. Finally, to co-optimize peptide permeability and KRAS binding affinity, we propose a step-by-step optimization strategy, demonstrating its effectiveness in generating molecules fulfilling both criteria. In conclusion, the HELM-GPT method can be used to identify novel macrocyclic peptides to target intracellular proteins. AVAILABILITY AND IMPLEMENTATION: The code and data of HELM-GPT are freely available on GitHub (https://github.com/charlesxu90/helm-gpt).
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Péptidos Cíclicos , Péptidos Cíclicos/química , Biología Computacional/métodos , Diseño de Fármacos , Péptidos/química , Humanos , Algoritmos , Programas InformáticosRESUMEN
All-polymer solar cells have experienced rapid development in recent years by the emergence of polymerized small molecular acceptors (PSMAs). However, the strong chain entanglements of polymer donors (PDs) and polymer acceptors (PAs) decrease the miscibility of the resulting polymer mixtures, making it challenging to optimize the blend morphology. Herein, we designed three PAs, namely PBTPICm-BDD, PBTPICγ-BDD and PBTPICF-BDD, by smartly using a BDD unit as the polymerized unit to copolymerize with different Y-typed non-fullerene small molecular acceptors (NF-SMAs), thus achieving a certain degree of distortion and giving the polymer system enough internal space to reduce the entanglements of the polymer chains. Such effects increase the chances of the PD being interspersed into the acceptor material, which improve the solubility between the PD and PA. The PBTPICγ-BDD and PBTPICF-BDD displayed better miscibility with PBQx-TCl, leading to a well optimized morphology. As a result, high power conversion efficiencies (PCEs) of 17.50 % and 17.17 % were achieved for PBQx-TCl : PBTPICγ-BDD and PBQx-TCl : PBTPICF-BDD devices, respectively. With the addition of PYFT-o as the third component into PBQx-TCl : PBTPICγ-BDD blend to further extend the absorption spectral coverage and finely tune microstructures of the blend morphology, a remarkable PCE of 18.64 % was realized finally.
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Systemic lupus erythematosus (SLE) is recognized as a prevalent autoimmune disorder characterized by a multifaceted pathogenesis potentially influenced by a combination of environmental factors, genetic predisposition, and hormonal regulation. The continuous study of immune system activation is especially intriguing. Analysis of blood samples from individuals with SLE reveals an abnormal increase in interferon levels, along with the existence of anti-double-stranded DNA antibodies. This evidence suggests that the development of SLE may be initiated by innate immunity. The presence of abnormal dsDNA fragments can activate DNA sensors within cells, particularly immune cells, leading to the initiation of downstream signaling cascades that result in the upregulation of relevant cytokines and the subsequent initiation of adaptive immune responses, such as B cell differentiation and T cell activation. The intricate pathogenesis of SLE results in DNA sensors exhibiting a wide range of functions in innate immune responses that are subject to variation based on cell types, developmental processes, downstream effector signaling pathways and other factors. The review aims to reorganize how DNA sensors influence signaling pathways and contribute to the development of SLE according to current studies, with the aspiration of furnishing valuable insights for future investigations into the pathological mechanisms of SLE and potential treatment approaches.
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ADN , Inmunidad Innata , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , ADN/inmunología , Animales , Transducción de Señal , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Citocinas/metabolismo , Citocinas/inmunologíaRESUMEN
The JAK-STAT pathway is a central communication node for various biological processes. Its activation is characterized by phosphorylation and nuclear translocation of the transcription factor STAT. The regulatory balance of JAK-STAT signaling is important for maintenance of immune homeostasis. Protein tyrosine phosphatases (PTPs) induce dephosphorylation of tyrosine residues in intracellular proteins and generally function as negative regulators in cell signaling. However, the roles of PTPs in JAK-STAT signaling, especially in invertebrates, remain largely unknown. Pacific white shrimp Penaeus vannamei is currently an important model for studying invertebrate immunity. This study identified a novel member of the dual-specificity phosphatase (DUSP) subclass of the PTP superfamily in P. vannamei, named PvDUSP14. By interacting with and dephosphorylating STAT, PvDUSP14 inhibits the excessive activation of the JAK-STAT pathway, and silencing of PvDUSP14 significantly enhances humoral and cellular immunity in shrimp. The promoter of PvDUSP14 contains a STAT-binding motif and can be directly activated by STAT, suggesting that PvDUSP14 is a regulatory target gene of the JAK-STAT pathway and mediates a negative feedback regulatory loop. This feedback loop plays a role in maintaining homeostasis of JAK-STAT signaling and is involved in antibacterial and antiviral immune responses in shrimp. Therefore, the current study revealed a novel inhibitory mechanism of JAK-STAT signaling, which is of significance for studying the regulatory mechanisms of immune homeostasis in invertebrates.
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Retroalimentación Fisiológica , Quinasas Janus , Penaeidae , Factores de Transcripción STAT , Transducción de Señal , Animales , Penaeidae/inmunología , Penaeidae/genética , Transducción de Señal/inmunología , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Fosforilación , Fosfatasas de Especificidad Dual/metabolismo , Fosfatasas de Especificidad Dual/genética , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/metabolismoRESUMEN
Chemodynamic therapy (CDT) is a novel antitumor strategy that employs Fenton or Fenton-like reactions to generate highly toxic hydroxyl radical (OHâ¢) from hydrogen peroxide (H2O2) for inducing tumor cell death. However, the antitumor efficacy of the CDT strategy is harshly limited by the redox homeostasis of tumor cells; especially the OH ⢠is easily scavenged by glutathione (GSH) and the intracellular H2O2 level is insufficient in the tumor cells. Herein, we propose the Mn2+-menadione (also known as vitamin K3, MK3) cascade biocatalysis strategy to disrupt the redox homeostasis of tumor cells and induce a OH⢠storm, resulting in enhanced CDT effect. A nanoliposome encapsulating Mn-MK3 (Mn-MK3@LP) was prepared for the treatment of hepatic tumors in this study. After Mn-MK3@LPs were taken up by tumor cells, menadione could facilitate the production of intracellular H2O2 via redox cycling, and further the cytotoxic OH ⢠burst was induced by Mn2+-mediated Fenton-like reaction. Moreover, high-valent manganese ions were reduced by GSH and the depletion of GSH further disrupted the redox homeostasis of tumor cells, thus achieving synergistically enhanced CDT. Overall, both cellular and animal experiments confirmed that the Mn-MK3@LP cascade biocatalysis nanoliposome exhibited excellent biosafety and tumor suppression efficacy. This study may provide deep insights for developing novel CDT-based strategies for tumor therapy.
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Glutatión , Peróxido de Hidrógeno , Radical Hidroxilo , Vitamina K 3 , Animales , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Humanos , Ratones , Glutatión/metabolismo , Glutatión/química , Vitamina K 3/química , Vitamina K 3/farmacología , Biocatálisis , Línea Celular Tumoral , Manganeso/química , Oxidación-Reducción/efectos de los fármacos , Ratones Endogámicos BALB C , Liposomas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones Desnudos , Células Hep G2 , Antineoplásicos/farmacología , Antineoplásicos/química , Nanopartículas/química , HierroRESUMEN
Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.
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Conexina 43 , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Calcio/metabolismo , Conexinas/metabolismo , Conexinas/farmacología , Transducción de Señal , Uniones Comunicantes , Comunicación CelularRESUMEN
A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.
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Volatile solid additives have attracted increasing attention in optimizing the morphology and improving the performance of currently dominated non-fullerene acceptor-based organic solar cells (OSCs). However, the underlying principles governing the rational design of volatile solid additives remain elusive. Herein, a series of efficient volatile solid additives are successfully developed by the crossbreeding effect of chalcogenation and iodination for optimizing the morphology and improving the photovoltaic performances of OSCs. Five benzene derivatives of 1,4-dimethoxybenzene (DOB), 1-iodo-4-methoxybenzene (OIB), 1-iodo-4-methylthiobenzene (SIB), 1,4-dimethylthiobenzene (DSB) and 1,4-diiodobenzene (DIB) are systematically studied, where the widely used DIB is used as the reference. The effect of chalcogenation and iodination on the overall property is comprehensively investigated, which indicates that the versatile functional groups provided various types of noncovalent interactions with the host materials for modulating the morphology. Among them, SIB with the combination of sulphuration and iodination enabled more appropriate interactions with the host blend, giving rise to a highly ordered molecular packing and more favorable morphology. As a result, the binary OSCs based on PM6:L8-BO and PBTz-F:L8-BO as well as the ternary OSCs based on PBTz-F:PM6:L8-BO achieved impressive high PCEs of 18.87%, 18.81% and 19.68%, respectively, which are among the highest values for OSCs.
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The burning loss of Al and Ti elements in superalloys during electroslag remelting has become a prevalent issue. And the existing slag system is not suitable for smelting the ATI 718PlusTM alloy. Therefore, it is imperative to develop a new slag system for smelting the ATI 718PlusTM alloy. To mitigate this issue, a thermodynamic model of the oxidation reaction of Al and Ti at the slag and alloy interface was established based on the ion and molecule coexistence theory (IMCT). The thermodynamic model was used to investigate the correlation between the equilibrium content of Al and Ti, slag composition, smelting temperature, and initial Al and Ti content of the electrode. The results indicate that while increasing the smelting temperature can effectively inhibit the burning loss of Al, it will exacerbate the burning loss of Ti. Increasing CaO and Al2O3 contents can inhibit the Al burning loss, while an increase in the TiO2 content can inhibit the Ti burning loss. Although an increase in the MgO content results in the burning loss of Al, its impact on the Al is minimal. The burning loss of Al and Ti was not affected by the change in the CaF2 content. The high Al content in ATI 718PlusTM makes it prone to burning loss of Al during the electroslag remelting. The combustion loss of Al can be reduced by increasing the Ti content in the electrode or adding a suitable amount of aluminum powder to the slag system. The accuracy of the model had been validated through experimental verification.
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Double-stranded RNA (dsRNA) can specifically inhibit gene expression by RNA interference and has important application potential in animal disease control. White spot syndrome virus (WSSV) is one of the most harmful pathogens in shrimp aquaculture, causing huge economic losses every year. In this study, we investigated the function of the WSSV-encoded wsv108 protein. We demonstrated that wsv108 could promote apoptosis by interacting with heat shock protein 70 (HSP70) and enhancing the expression of multiple apoptosis-related genes. Silencing of wsv108 gene by injection with specific dsRNA prepared by in vitro transcription significantly increased the survival rate of WSSV-infected shrimp and reduced the viral load in tissues, suggesting that wsv108 is important for WSSV pathogenicity. Based on this, we expressed the wsv108 specific dsRNA in engineered Escherichia coli. Oral feeding of this bacterium could inhibit the expression of wsv108, increase the survival rate of WSSV-infected shrimp, and decrease the viral load of WSSV in tissues. Therefore, this study developed a new method for treatment of WSSV disease by oral administration of bacterially expressed dsRNA against a novel therapeutic target molecule, which could be a potential candidate strategy for WSSV control in aquaculture.
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Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Virus del Síndrome de la Mancha Blanca 1/genética , ARN Bicatenario/genética , Interferencia de ARN , Penaeidae/genéticaRESUMEN
Plants rely on systemic signalling mechanisms to establish whole-body defence in response to insect and nematode attacks. GLUTAMATE RECEPTOR-LIKE (GLR) genes have been implicated in long-distance transmission of wound signals to initiate the accumulation of the defence hormone jasmonate (JA) at undamaged distal sites. The systemic signalling entails the activation of Ca2+-permeable GLR channels by wound-released glutamate, triggering membrane depolarization and cytosolic Ca2+ influx throughout the whole plant. The systemic electrical and calcium signals rapidly dissipate to restore the resting state, partially due to desensitization of the GLR channels. Here we report the discovery of calmodulin-mediated, Ca2+-dependent desensitization of GLR channels, revealing a negative feedback loop in the orchestration of plant systemic wound responses. A CRISPR-engineered GLR3.3 allele with impaired desensitization showed prolonged systemic electrical signalling and Ca2+ waves, leading to enhanced plant defence against herbivores. Moreover, this Ca2+/calmodulin-mediated desensitization of GLR channels is a highly conserved mechanism in plants, providing a potential target for engineering anti-herbivore defence in crops.
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Proteínas de Arabidopsis , Arabidopsis , Calmodulina , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transducción de Señal/genética , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo , Plantas/metabolismoRESUMEN
The limited selection of wide bandgap polymer donors for all-polymer solar cells (all-PSCs) is a bottleneck problem restricting their further development and remains poorly studied. Herein, a new wide bandgap polymer, namely PBBTz-Cl, is designed and synthesized by bridging the benzobisthiazole acceptor block and chlorinated benzodithiophene donor block with thiophene units for application as an electron donor in all-PSCs. PBBTz-Cl not only possesses wide bandgap and deep energy levels but also displays strong absorption, high-planar structure, and good crystallinity, making it a promising candidate for application as a polymer donor in organic solar cells. When paired with the narrow bandgap polymer acceptor PY-IT, a fibril-like morphology forms, which facilitates exciton dissociation and charge transport, contributing to a power conversion efficiency (PCE) of 17.15% of the corresponding all-PSCs. Moreover, when introducing another crystalline polymer acceptor BTP-2T2F into the PBBTz-Cl:PY-IT host blend, the absorption ditch in the range of 600-750 nm is filled, and the blend morphology is further optimized with the trap density reducing. As a result, the ternary blend all-PSCs achieve a significantly improved PCE of 18.60%, which is among the highest values for all-PSCs to date.
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Minimizing interfacial charged traps in perovskite films is crucial for reducing the non-radiative recombination and improving device performance. In this study, succinic acid (SA) derivatives varying active sites and spatial configurations are designed to modulate defects and crystallization in perovskite film. The SA derivative with two symmetric Br atoms, dibromosuccinic acid (DBSA), exhibits the optimal spatial arrangement for defect passivation. Experimental and theoretical results indicate that the carboxyl group and atomic Br in DBSA synergistically interact with the under-coordinated Pb2+ . Moreover, the strong electronegativity of Br efficiently stabilizes the formamidinium cation via electrostatic interaction. Consequently, film quality is significantly improved and non-radiative recombination is markedly depressed, resulting in a photoluminesence lifetime of exceeding 4 µs of and a carrier diffusion length of 3 µm. An exceptional efficiency of 25.41% (certified at 25.00%) along with a high fill factor of 84.39% and excellent long-term operational stability have been achieved finally.
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Heterogeneous data is endemic due to the use of diverse models and settings of devices by hospitals in the field of medical imaging. However, there are few open-source frameworks for federated heterogeneous medical image analysis with personalization and privacy protection without the demand to modify the existing model structures or to share any private data. Here, we proposed PPPML-HMI, a novel open-source learning paradigm for personalized and privacy-preserving federated heterogeneous medical image analysis. To our best knowledge, personalization and privacy protection were discussed simultaneously for the first time under the federated scenario by integrating the PerFedAvg algorithm and designing the novel cyclic secure aggregation with the homomorphic encryption algorithm. To show the utility of PPPML-HMI, we applied it to a simulated classification task namely the classification of healthy people and patients from the RAD-ChestCT Dataset, and one real-world segmentation task namely the segmentation of lung infections from COVID-19 CT scans. Meanwhile, we applied the improved deep leakage from gradients to simulate adversarial attacks and showed the strong privacy-preserving capability of PPPML-HMI. By applying PPPML-HMI to both tasks with different neural networks, a varied number of users, and sample sizes, we demonstrated the strong generalizability of PPPML-HMI in privacy-preserving federated learning on heterogeneous medical images.
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COVID-19 , Privacidad , Humanos , Algoritmos , Hospitales , AprendizajeRESUMEN
The success of Y6-type nonfullerene small molecule acceptors (NF-SMAs) in polymer solar cells (PSCs) can be attributed to their unique honeycomb stacking style, which leads to favorable thin-film morphologies. The intermolecular interactions related to the crystallization tendency of these NF-SMAs is closely governed by their electron accepting end groups. For example, the high performance Y6 derivative L8-BO (BTP-4F) presents three types of stacking modes in contrast to two stacking modes of Y6. Hence, it is ultimately interesting to obtain more insight on the packing properties and the preferences influenced by chemical modifications such as end group engineering. This work designs and synthesizes asymmetric and symmetric L8-BO derivatives with brominated end groups and explores the stacking preferences in various modes. The asymmetric BTP-3FBr displays an optimized crystallization tendency and thin film morphology, leading to a decent power conversion efficiency (PCE) of 18.34% in binary devices and a top PCE of 19.32% in ternary devices containing 15 wt% IDIC as the second acceptor.
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The NF-κB pathway plays an important role in immune regulation. Basigin, an immunoglobulin superfamily membrane protein, is involved in the activation of NF-κB. However, its role in NF-κB signaling in response to pathogen infection remains unclear. In this study, we identified the Basigin gene from Pacific white shrimp, Penaeus vannamei, a representative species for studying the innate immune system of invertebrates. Basigin promoted the degradation of the IκB homolog Cactus, facilitated the nuclear translocation of the NF-κB family member Dorsal, and positively regulated the expression of Dorsal pathway downstream antimicrobial peptide genes. Interestingly, recombinant Basigin protein could bind a variety of Gram-positive and Gram-negative bacteria. Silencing of Basigin inhibited the Dorsal signaling activated by V. parahaemolyticus infection and significantly decreased the survival rate of V. parahaemolyticus-infected shrimp. The expression levels of the antimicrobial peptides ALF1 and ALF2 were downregulated, and the phagocytosis of hemocytes was attenuated in Basigin-silenced shrimp. Similar results were observed in shrimp treated with a recombinant extracellular region of the Basigin protein that was able to compete with endogenous Basigin. Therefore, to the best of our knowledge, this study is the first to demonstrate the function of Basigin as a pathogen recognition receptor that activates NF-κB signaling for antibacterial immunity in shrimp.
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Penaeidae , Vibrio parahaemolyticus , Virus del Síndrome de la Mancha Blanca 1 , Animales , FN-kappa B/metabolismo , Basigina , Antibacterianos , Proteínas de Artrópodos , Bacterias Gramnegativas , Bacterias Grampositivas , Inmunidad Innata/genética , Vibrio parahaemolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiologíaRESUMEN
IMPORTANCE: Viruses are able to mimic the physiological or pathological mechanism of the host to favor their infection and replication. Virus-mock basement membrane (VMBM) is a Megalocytivirus-induced extracellular structure formed on the surface of infected cells and structurally and functionally mimics the basement membrane of the host. VMBM provides specific support for lymphatic endothelial cells (LECs) rather than blood endothelial cells to adhere to the surface of infected cells, which constitutes a unique phenomenon of Megalocytivirus infection. Here, the structure of VMBM and the interactions between VMBM components and LECs have been analyzed at the molecular level. The regulatory effect of VMBM components on the proliferation and migration of LECs has also been explored. This study helps to understand the mechanism of LEC-specific attachment to VMBM and to address the issue of where the LECs come from in the context of Megalocytivirus infection.
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Membrana Basal , Células Endoteliales , Iridoviridae , Vasos Linfáticos , Membrana Basal/metabolismo , Membrana Basal/virología , Células Endoteliales/citología , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Iridoviridae/fisiología , Vasos Linfáticos/citología , Proliferación Celular , Movimiento Celular , Vasos Sanguíneos/citología , Interacciones Microbiota-HuespedRESUMEN
Modification of the molecular packing of nonfullerene acceptors through fluorination represents one of the most promising strategies to achieve highly efficient organic solar cells (OSCs). In this work, three nonfused electron acceptors, namely, DTCBT-Fx (x = 0, 5, 9) with precisely controlled amounts of fluorine atoms in the side chains are designed and synthesized, and the effect of side chain fluorination is systematically studied. The results demonstrate that the light absorption, energy levels, molecular ordering, and film morphology could be effectively tuned by precisely controlling the side chain fluorination. DTCBT-F5 with an appropriate fluorine functionalization exhibits suitable miscibility with the donor polymer (PM6), leading to diminished charge recombination and improved charge carrier mobility. Consequently, a promising power conversion efficiency of 12.7% was obtained for DTCBT-F5-based solar cells, which outperforms those OSCs based on DTCBT-F0 (11.4%) and DTCBT-F9 (11.6%), respectively. This work demonstrates that precise control of the fluorine functionalization in side chains of nonfused electron acceptors is an effective strategy for realizing highly efficient OSCs.