The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have improved considerably in recent years with the development of fused‐ring electron acceptors (FREAs). Currently, FREAs‐based ...OSCs have achieved high PCEs of over 19% in single‐junction OSCs. Whereas the relatively high synthetic complexity and the low yield of FREAs typically result in high production costs, hindering the commercial application of OSCs. In contrast, noncovalently fused‐ring electron acceptors (NFREAs) can compensate for the shortcomings of FREAs and facilitate large‐scale industrial production by virtue of the simple structure, facile synthesis, high yield, low cost, and reasonable efficiency. At present, OSCs based on NFREAs have exceeded the PCEs of 15% and are expected to reach comparable efficiency as FREAs‐based OSCs. Here, recent advances in NFREAs in this review provide insight into improving the performance of OSCs. In particular, this paper focuses on the effect of the chemical structures of NFREAs on the molecule conformation, aggregation, and packing mode. Various molecular design strategies, such as core, side‐chain, and terminal group engineering, are presented. In addition, some novel polymer acceptors based on NFREAs for all‐polymer OSCs are also introduced. In the end, the paper provides an outlook on developing efficient, stable, and low‐cost NFREAs for achieving commercial applications.
Noncovalently fused‐ring electron acceptors (NFREAs) have attracted much attention because of the advantage of simple structure, facile synthesis, and low cost, which have great potential for commercial applications in organic solar cells. This review presents the recent development of NFREAs for organic solar cells and focuses on the effect of their chemical structure on the molecule conformation, aggregation, and packing structure.
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy ...person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown.
Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19.
We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients.
Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions.
National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program.
Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex ...(LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB-mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow-derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L(-/-) mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients.
This study aimed to investigate dental pulp responses to novel bioactive glass (BG) pulp capping materials after direct pulp capping in vivo.
Novel BG pulp capping materials are composed of powder ...and fluid. The powder is BG (82.36% SiO2, 15.36% CaO, and 2.28% P2O5), and the fluid is provided in 2 kinds: (1) phosphate buffer solution (BG-PB) and (2) phosphate buffer solution with the addition of 1 wt% sodium alginate (BG-PB-SA). After mixing the powder and fluid, BG-PB and BG-PB-SA were prepared. Cavities with mechanical pulp exposure were prepared on maxillary first molars of Wistar rats. The exposures were randomly capped with BG-PB, BG-PB-SA, or mineral trioxide aggregate (MTA). After 1 (n = 6) and 4 weeks (n = 8), maxillary segments were obtained and prepared for histologic analysis with a scoring system. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney U tests with the significance set at .05.
After 1 week, few inflammatory cells were present in the BG-PB, BG-PB-SA, and MTA groups. Moreover, a thin layer of newly generated matrix was observed in most specimens. After 4 weeks, all specimens from the 3 groups formed a heavy dentin bridge. BG-PB and BG-PB-SA groups exhibited no or slight inflammatory response, whereas the MTA group exhibited a slight to moderate inflammatory response. No significant difference was observed in pulp inflammation and dentin formation among the 3 groups at either time point (P > .05).
When used as a pulp capping agent, BG-PB and BG-PB-SA had similar favorable cellular and inflammatory pulp responses to those of MTA. Therefore, BG is a promising pulp capping material.
•Direct pulp capping on a rat first maxillary model was built.•Two kinds of bioactive glass (BG) pulp capping materials, namely BG-PB and BG-PB-SA were tested.•Histologic sections were made and stained; we evaluated the sections using a scoring system.•BG-PB and BG-PB-SA showed similar favorable responses with MTA on direct pulp capping.
Robust immune responses are essential for eliminating pathogens but must be metered to avoid prolonged immune activation and potential host damage. Upon recognition of microbial DNA, the cytosolic ...DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent interferon (IFN) production. We report that the direct interaction between cGAS and the Beclin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stranded DNA (dsDNA) stimulation or herpes simplex virus-1 infection, but also enhances autophagy-mediated degradation of cytosolic pathogen DNA to prevent excessive cGAS activation and persistent immune stimulation. Specifically, this interaction releases Rubicon, a negative autophagy regulator, from the Beclin-1 complex, activating phosphatidylinositol 3-kinase class III activity and thereby inducing autophagy to remove cytosolic pathogen DNA. Thus, the cGAS-Beclin-1 interaction shapes innate immune responses by regulating both cGAMP production and autophagy, resulting in well-balanced antimicrobial immune responses.
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•DNA sensor cGAS binds Beclin-1 autophagy protein upon HSV infection or DNA exposure•Beclin-1 binding deregulates cGAS activity to block cGAMP and IFN production•cGAS binding to Beclin-1 releases Rubicon, inducing autophagy of cytosolic DNA
Antimicrobial responses limit infection but require regulation to prevent host damage. Liang et al. show that crosstalk between the DNA sensor cGAS and Beclin-1 autophagy protein not only suppresses cGAS to halt cGAMP and subsequent interferon production, but also enhances autophagy-mediated degradation of microbial DNA to avoid persistent immune stimulation.
RSK1, an essential cellular kinase for Kaposi's sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate ...phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosphorylation via two separated functional regions: SIMs and amino acid 17-90, respectively, which do not affect each other. Similar to KSHV ORF45, ORF45 of Rhesus Macaque Rhadinovirus has only one SIM and also increases RSK1 SUMOylation in a SIM-dependent manner, while other ORF45 homologues do not have this function. Our work characterized ORF45 as a novel virus encoded SUMO E3 ligase, which is required for ORF45-RSK1 axis-mediated KSHV lytic gene expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS) synthesizes the second messenger cyclic GMP-AMP (cGAMP) that binds to the STING, triggering antiviral interferon-β (IFN-β) production. However, it ...has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts’ immune responses to DNA stimulation.
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•Akt-mediated phosphorylation robustly suppresses cGAS enzymatic activity•Akt-mediated phosphorylation changes cytokine production and HSV-1 replication•Akt phosphorylation-resistant cGAS enhances IFN-β production upon virus infection
Although a robust cGAS-mediated antiviral response is essential for controlling viral infection, this response must be metered to avoid excessive production of cytokines. Seo et al. show that Akt phosphorylates cGAS and dampens its enzymatic activity as well as anti-viral activity in response to DNA stimulation and DNA virus infection.
Telemedicine imaging services usually require wireless transmission of a large number of medical images MRI/CT, etc., in the network, which are subject to noise interference and block effect during ...transmission and compression, leading to degradation of image reconstruction quality, thus affecting diagnostic accuracy. In this paper, iterative shrinkage thresholding (ISTA)-based anti-noise compressive perceptual image reconstruction network is proposed to solve the problem. The network adopts a constrained sparse model, which incorporates both orthogonal and binary constraints of the sampling matrix into the network; in addition, the network adopts feature extraction subnetwork, parameter initialization subnetwork, and reconstruction anti-noise subnetwork for compressed perceptual image reconstruction, incorporates the channel attention mechanism, and proposes a hybrid network for anti-noise deblocking in the reconstruction anti-noise subnetwork. Experiments show that the maximum peak signal-to-noise ratio achievable by the network is in the range of 29.70–39.31 dB under different noise interference scenarios.
Open reading frame 45 (ORF45) of Kaposi sarcoma-associated herpesvirus (KSHV) causes sustained activation of p90 ribosomal S6 kinase (RSK), which is crucial for KSHV lytic replication, but the exact ...functional roles remain to be determined. To characterize the biological consequence of persistent RSK activation by ORF45, we screened known cellular substrates of RSK. We found that ORF45 induced phosphorylation of eukaryotic translation initiation factor 4B (eIF4B), increased its assembly into translation initiation complex, and subsequently facilitated protein translation. The ORF45/RSK-mediated eIF4B phosphorylation was distinguishable from that caused by the canonical AKT/mammalian target of rapamycin/ribosomal S6 kinase and MEK/ERK/RSK pathways because it was resistant to both rapamycin (an mammalian target of rapamycin inhibitor) and U1026 (an MEK inhibitor). The rapamycin and U1026 doubly insensitive eIF4B phosphorylation was induced during KSHV reactivation but was abolished if either ORF45 or RSK1/2 were ablated by siRNA, a pattern that is correlated with reduced lytic gene expression as we observed previously. Ectopic expression of eIF4B but not its phosphorylation-deficient mutant form increased KSHV lytic gene expression and production of progeny viruses. Together, these results indicated that ORF45/RSK axis-induced eIF4B phosphorylation is involved in translational regulation and is required for optimal KSHV lytic replication.
Background: ORF45 of Kaposi sarcoma-associated herpesvirus (KSHV) causes sustained activation of p90 ribosomal S6 kinases (RSKs).
Results: ORF45 increases phosphorylation of eIF4B through p90 RSKs.
Conclusion: The ORF45/RSK axis promotes protein translation during lytic replication.
Significance: This mechanism is crucial for understanding of translational regulation during KSHV lytic replication.
RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi's ...sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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