Virus infection has drawn extensive attention since it causes serious or even deadly diseases, consequently inducing a series of social and public health problems. Caveolin-1 is the most important ...structural protein of caveolae, a membrane invagination widely known for its role in endocytosis and subsequent cytoplasmic transportation. Caveolae/caveolin-1 is tightly associated with a wide range of biological processes, including cholesterol homeostasis, cell mechano-sensing, tumorigenesis, and signal transduction. Intriguingly, the versatile roles of caveolae/caveolin-1 in virus infections have increasingly been appreciated. Over the past few decades, more and more viruses have been identified to invade host cells via caveolae-mediated endocytosis, although other known pathways have been explored. The subsequent post-entry events, including trafficking, replication, assembly, and egress of a large number of viruses, are caveolae/caveolin-1-dependent. Deprivation of caveolae/caveolin-1 by drug application or gene editing leads to abnormalities in viral uptake, viral protein expression, or virion release, whereas the underlying mechanisms remain elusive and must be explored holistically to provide potential novel antiviral targets and strategies. This review recapitulates our current knowledge on how caveolae/caveolin-1 functions in every step of the viral infection cycle and various relevant signaling pathways, hoping to provide a new perspective for future viral cell biology research.
Alpha7 nicotinic acetylcholine receptor (α7 nAChR), a hub of the cholinergic anti-inflammatory pathway (CAP), is required for the treatment of inflammatory diseases. HIV-1 infection can upregulate ...the expression of α7 nAChR in T lymphocytes and affect the role of CAP. However, whether α7 nAChR regulates HIV-1 infection in CD4+ T cells is unclear. In this study, we first found that activation of α7 nAChR by GTS-21 (an α7 nAChR agonist) can promote the transcription of HIV-1 proviral DNA. Then, through transcriptome sequencing analysis, we found that p38 MAPK signaling was enriched in GTS-21 treated HIV-latent T cells. Mechanistically, activation of α7 nAChR could increase reactive oxygen species (ROS), reduce DUSP1 and DUSP6, and consequently enhance the phosphorylation of p38 MAPK. By co-immunoprecipitation and liquid chromatography tandem mass spectrometry, we found that p-p38 MAPK interacted with Lamin B1 (LMNB1). Activation of α7 nAChR increased the binding between p-p38 MAPK and LMNB1. We confirmed that knockdown of MAPK14 significantly downregulated NFATC4, a key activator of HIV-1 transcription. Taken together, activation of the α7 nAChR could trigger ROS/p-p38 MAPK/LMNB1/NFATC4 signaling pathway enhancing HIV-1 transcription. We have revealed an unrecognized mechanism of α7 nAChR-mediated neuroimmune regulation of HIV infection.
Whether α7 nAChR regulates HIV-1 infection in CD4+ T cells is unclear. Wen et al. reveal that activation of the α7 nAChR could trigger ROS/p38 MAPK/LMNB1/NFATC4 signaling pathway enhancing HIV-1 transcription. Display omitted
•Activation of α7 nAChR promotes HIV-1 transcriptional initiation.•Activation of α7 nAChR reduces phosphorylation of p38 MAPK.•Phosphorylation of p38 MAPK is required for α7 nAChR-mediated HIV transcription.•Activation of α7 nAChR promotes HIV-1 transcription depending on interaction between p-p38 MAPK and LMNB1.
Abstract
The emerging coronavirus (CoV) pandemic is threatening the public health all over the world. Cytoskeleton is an intricate network involved in controlling cell shape, cargo transport, signal ...transduction, and cell division. Infection biology studies have illuminated essential roles for cytoskeleton in mediating the outcome of host‒virus interactions. In this review, we discuss the dynamic interactions between actin filaments, microtubules, intermediate filaments, and CoVs. In one round of viral life cycle, CoVs surf along filopodia on the host membrane to the entry sites, utilize specific intermediate filament protein as co-receptor to enter target cells, hijack microtubules for transportation to replication and assembly sites, and promote actin filaments polymerization to provide forces for egress. During CoV infection, disruption of host cytoskeleton homeostasis and modification state is tightly connected to pathological processes, such as defective cytokinesis, demyelinating, cilia loss, and neuron necrosis. There are increasing mechanistic studies on cytoskeleton upon CoV infection, such as viral protein‒cytoskeleton interaction, changes in the expression and post-translation modification, related signaling pathways, and incorporation with other host factors. Collectively, these insights provide new concepts for fundamental virology and the control of CoV infection.
Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause ...severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced the ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.
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Su and colleagues find that activation of α7 nAChR significantly limits ZIKV infection by enhancing autophagy and ferroptosis. Moreover, α7 nAChR is essential to control ZIKV-induced disease severity in neonatal mice. Harnessing α7 nAChR activation holds promising potential as a novel strategy to combat ZIKV infection and its associated complications.
Erythroleukemia belongs to acute myeloid leukemia (AML) type 6 (M6), and treatment remains difficult due to the poor prognosis of the disease. Friend virus (FV) is a complex of two viruses: Friend ...murine leukemia virus (F-MuLV) strain along with a defective spleen focus-forming virus (SFFV), which can induce acute erythroleukemia in mice. We have previously reported that activation of vagal α7 nicotinic acetylcholine receptor (nAChR) signaling promotes HIV-1 transcription. Whether vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain unclear. In this study, sham and vagotomized mice were intraperitoneally injected with FV. FV infection caused anemia in sham mice, and vagotomy reversed this change. FV infection increased erythroblasts ProE, EryA, and EryB cells in the spleen, and these changes were blocked by vagotomy. In bone marrow, FV infection reduced EryC cells in sham mice, an effect that was counteracted by vagotomy. FV infection increased choline acetyltransferase (ChAT) expression in splenic CD4+ and CD8+ T cells, and this change was reversed by vagotomy. Furthermore, the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4+ T cells. In bone marrow, FV infection reduced EryB and EryC cells in sham mice, whereas lack of ChAT in CD4+ T cells did not affect this change. Activation of muscarinic acetylcholine receptor 4 (mAChR4) by clozapine N-oxide (CNO) significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected mice. Thus, vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute erythroleukemia. We uncover an unrecognized mechanism of neuromodulation in erythroleukemia.
•Vagotomy reverses FV infection-induced increases in ProE, EryA, and EryB cells in the spleen.•Vagotomy can counteract the decrease in EryC cells in the bone marrow caused by FV infection.•Deletion of ChAT in CD4+ T cells reverses the increase in EryA and EryB cells in FV infected spleen.•Activation of mAChR4 increases spleen EryB but decreases bone marrow EryC cell populations from FV-infected mice.
3D referring expression comprehension (3DREC) and segmentation (3DRES) have overlapping objectives, indicating their potential for collaboration. However, existing collaborative approaches ...predominantly depend on the results of one task to make predictions for the other, limiting effective collaboration. We argue that employing separate branches for 3DREC and 3DRES tasks enhances the model's capacity to learn specific information for each task, enabling them to acquire complementary knowledge. Thus, we propose the MCLN framework, which includes independent branches for 3DREC and 3DRES tasks. This enables dedicated exploration of each task and effective coordination between the branches. Furthermore, to facilitate mutual reinforcement between these branches, we introduce a Relative Superpoint Aggregation (RSA) module and an Adaptive Soft Alignment (ASA) module. These modules significantly contribute to the precise alignment of prediction results from the two branches, directing the module to allocate increased attention to key positions. Comprehensive experimental evaluation demonstrates that our proposed method achieves state-of-the-art performance on both the 3DREC and 3DRES tasks, with an increase of 2.05% in Acc@0.5 for 3DREC and 3.96% in mIoU for 3DRES.
Recent advancements in automatic 3D avatar generation guided by text have
made significant progress. However, existing methods have limitations such as
oversaturation and low-quality output. To ...address these challenges, we propose
X-Oscar, a progressive framework for generating high-quality animatable avatars
from text prompts. It follows a sequential Geometry->Texture->Animation
paradigm, simplifying optimization through step-by-step generation. To tackle
oversaturation, we introduce Adaptive Variational Parameter (AVP), representing
avatars as an adaptive distribution during training. Additionally, we present
Avatar-aware Score Distillation Sampling (ASDS), a novel technique that
incorporates avatar-aware noise into rendered images for improved generation
quality during optimization. Extensive evaluations confirm the superiority of
X-Oscar over existing text-to-3D and text-to-avatar approaches. Our anonymous
project page: https://xmu-xiaoma666.github.io/Projects/X-Oscar/.
Dielectric elastomer actuators (DEAs) with large actuation strain and high energy density are highly desirable for actuating soft robots. However, DEAs usually require high driving electric fields ...(>100 MV m
) to achieve high performances due to the low dielectric constant and high stiffness of dielectric elastomers (DEs). Here, we introduce polar fluorinated groups and nanodomains aggregated by long alkyl side chains into DE design, simultaneously endowing DE with a high dielectric constant and desirable modulus. Our DE exhibits a maximum area strain of 253% at a low driving electric field of 46 MV m
. Notably, it achieves an ultrahigh specific energy of 225 J kg
at only 40 MV m
, around 6 times higher than natural muscle and twice higher than the state-of-the-art DE. Using our DE, soft robots reach an ultrafast running speed of 20.6 BL s
, 60 times higher than that of commercial VHB 4910, representing the fastest DEA-driven soft robots ever reported.
Abstract Stretchable dielectric polymer with high dielectric constant is a major component for electroluminescent devices. However, the intrinsic instability toward water severely limits their ...further applications in marine environment. Here, a transparent, underwater stable, and self‐healable dielectric material with high dielectric constant is reported. The electroluminescent device based on this newly designed fluoropolymer can work stably in aqueous conditions. There is no significant attenuation of mechanical and optoelectronic property after immersed in water and salty water for a month. The intrinsic self‐healing ability of the device makes it robust and resilient against unexpected minor or severe damages.
Hyperelastic materials exhibit a nonlinear elastic response to large strains, whereas hydrogels typically possess a low elastic range due to the nonuniform cross-linking and limited chain segments ...among cross-links. We developed a hyperelastic hydrogel that possesses a broader elastic range by introducing a reversible pearl-necklace structure, in which beads are connected by strings. The subnanometric beads can efficiently unfold and refold under cyclic mechanical strains; thus, the hydrogel can rapidly recover after being stretched to an areal strain of more than 10,000%. Additionally, the hydrogel can quickly heal from minor mechanical damages such as needle punctures and cuts. These advancements make our ionic hydrogels ideal for multifunctional pneumatic gripper materials; they simultaneously offer an ultralarge gripping range, self-sensing capabilities, and fast healing abilities.
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