Innate sensors recognize pathogen‐associated molecular patterns (PAMPs) or damage‐associated molecular patterns (DAMPs) to initiate innate immune response by activating downstream signaling. These ...evolutionarily conserved innate sensors usually locate in the plasma membrane or cytoplasm. However, the nucleus‐localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. Furthermore, these nuclear innate sensors evolve varied mechanisms for discriminating self from non‐self nucleic acids to maintain immune homeostasis and avoid autoinflammatory immune response. In this review, we summarize the recent findings on the identification of nuclear innate sensors for nucleic acids, such as hnRNPA2B1, IFI16, SAFA, and their roles in host defense and inflammatory response.
To realize the vision of “carbon neutrality” in China, the use of clean energy and hydrogen energy storages can be integrated to optimize the structure of power systems and ensure safe, stable, and ...low-carbon operation of power. However, the current cost of hydrogen production is primarily associated to the high price of electricity, and the construction of an integrated energy system is a promising approach to solve this problem. In this study, a solitary grid energy system that integrates water and hydrogen has been developed, which consists of a hydroelectric power station, hydrogen production equipment, a hydrogen storage device, and a fuel cell. Furthermore, a two-layer programming model is designed. The upper layer is aimed at minimizing the construction cost to improve the hydrogen production capacity, hydrogen storage, fuel cell performance, and other facilities. Meanwhile, the lower layer is aimed at minimizing the decrease in daily operations to optimize the utilization of all the facilities in the integrated energy system under different scenarios. The Asynchronous Advantage Actor-Critic (A3C) reinforcement learning algorithm and Gurobi are used to solve the model. The results of typical scenarios show that the water-hydrogen integrated energy system saves water resources, maintains the stability of electric power, and provides improved economic benefits than those offered by single hydroelectric systems, thereby increasing the overall resource, social, and economic values of the system.
An isolated water-hydrogen integrated energy coordination system was established, and its planning and operation scheduling were carried out. The research results verified its resource, social and economic advantages. Display omitted
•A water-hydrogen integrated energy complementary system is constructed.•A two-layer planning and operation scheduling model of the water-hydrogen integrated energy system is proposed.•A two-layer reinforcement learning algorithm is used to solve the planning problem.
Osteoprotegerin (OPG) is supposed to participate in the development of atherosclerosis and cardio-cerebrovascular disease. However, the results of research on relationship between OPG and ischemic ...stroke (IS) are controversial. Therefore, we carried out the first systematic review and meta-analysis to evaluate prognostic effect of osteoprotegerin in patients with IS.
We comprehensively searched databases of PubMed, Embase, and the Cochrane Library through 21 August 2023 to identify observational studies that evaluated effect of OPG on poor functional outcome (modified Rankin Scale mRS Score of 3-6) and mortality in patients with IS. Adjusted odds ratios (aOR) with a 95% confidence interval (CI) of each included study were used as much as possible to assess the pooled effect.
Five studies that enrolled 4,506 patients in total fulfilled our inclusion criteria. Three studies were included in the pooled analysis for each endpoint since one of the included studies had provided data on poor functional outcome as well as mortality. OPG was neither associated with poor functional outcome (aOR 1.29, 95% CI 0.90-1.85) nor with mortality (aOR 1.57, 95% CI 0.90-2.74) in patients with IS.
There is insufficient evidence to demonstrate the correlation between OPG and mortality or poor functional outcome in IS patients. OPG cannot be applied to predict worse neurological function in IS patients based on the current evidence.
The innate RNA sensor RIG-I is critical in the initiation of antiviral type I interferons (IFNs) production upon recognition of “non-self” viral RNAs. Here, we identify a host-derived, IFN-inducible ...long noncoding RNA, lnc-Lsm3b, that can compete with viral RNAs in the binding of RIG-I monomers and feedback inactivate the RIG-I innate function at late stage of innate response. Mechanistically, binding of lnc-Lsm3b restricts RIG-I protein’s conformational shift and prevents downstream signaling, thereby terminating type I IFNs production. Multivalent structural motifs and long-stem structure are critical features of lnc-Lsm3b for RIG-I binding and inhibition. These data reveal a non-canonical self-recognition mode in the regulation of immune response and demonstrate an important role of an inducible “self” lncRNA acting as a potent molecular decoy actively saturating RIG-I binding sites to restrict the duration of “non-self” RNA-induced innate immune response and maintaining immune homeostasis, with potential utility in inflammatory disease management.
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•lnc-Lsm3b competes with viral RNA for binding but stabilizing inactive RIG-I•Deficiency of lnc-Lsm3b specifically enhances RIG-I-initiated IFN production•Structural motifs of lnc-Lsm3b are vital for its optimal binding to RIG-I proteins•lnc-Lsm3b acts as a decoy for RIG-I and prevents downstream signaling
A self-recognition mode between RIG-I and an inducible host lncRNA functions to restrict innate immune response in a feedback manner.
Volcanic history of the Imbrium basin Zhang, Jinhai; Yang, Wei; Hu, Sen ...
Proceedings of the National Academy of Sciences - PNAS,
04/2015, Letnik:
112, Številka:
17
Journal Article
Recenzirano
Odprti dostop
We report the surface exploration by the lunar rover Yutu that landed on the young lava flow in the northeastern part of the Mare Imbrium, which is the largest basin on the nearside of the Moon and ...is filled with several basalt units estimated to date from 3.5 to 2.0 Ga. The onboard lunar penetrating radar conducted a 114-m-long profile, which measured a thickness of ∼5 m of the lunar regolith layer and detected three underlying basalt units at depths of 195, 215, and 345 m. The radar measurements suggest underestimation of the global lunar regolith thickness by other methods and reveal a vast volume of the last volcano eruption. The in situ spectral reflectance and elemental analysis of the lunar soil at the landing site suggest that the young basalt could be derived from an ilmenite- rich mantle reservoir and then assimilated by 10–20% of the last residual melt of the lunar magma ocean.
The helicase RIG-I initiates an antiviral immune response after recognition of pathogenic RNA. TRIM25, an E3 ubiquitin ligase, mediates K63-linked ubiquitination of RIG-I, which is crucial for RIG-I ...downstream signaling and the antiviral innate immune response. The components and mode of the RIG-I-initiated innate signaling remain to be fully understood. Here we identify a novel long noncoding RNA (Lnczc3h7a) that binds to TRIM25 and promotes RIG-I-mediated antiviral innate immune responses. Depletion of Lnczc3h7a impairs RIG-I signaling and the antiviral innate response to RNA viruses in vitro and in vivo. Mechanistically, Lnczc3h7a binds to both TRIM25 and activated RIG-I, serving as a molecular scaffold for stabilization of the RIG-I-TRIM25 complex at the early stage of viral infection. Lnczc3h7a facilitates TRIM25-mediated K63-linked ubiquitination of RIG-I and thus promotes downstream signaling transduction. Our findings reveal that host RNAs can enhance the response of innate immune sensors to foreign RNAs, ensuring effective antiviral defense.
Multinuclear complexes as metallo-agents for clinical use have caught extensive attention. In this paper, using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as both a functioning ...unit and a constructing junction, we build a series of DOTA-branched organic frameworks with multiple chelating holes by organizing DOTA layer by layer. These giant chelators are well characterized, which reveals their nanosized and soft structures. Further experiments demonstrate that they could efficiently hold abundant metal ions with much higher kinetic stabilities than the conventional small DOTA chelator. Their corresponding polynuclear complexes containing Gd3+, Tb3+, or both show superior imaging properties, excellent feasibility for peripheral modification, and unusual kinetic stability. This work can be easily extended to the fabrication of diverse homomultinuclear complexes and core/shell heteromultinuclear complexes with multifunctional properties. We expect that this new type of giant molecules and the ligand-branching strategy would open up a new avenue for the design and construction of next-generation polymetallic agents with high performance and stabilities for biomedical applications.
Tumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL) regulates multiple physiological or pathological functions, including osteoclast differentiation and osteoporosis. ...TNFRSF11A (also called RANK) is considered to be the sole receptor for RANKL. Herein we report that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL. LGR4 competes with RANK to bind RANKL and suppresses canonical RANK signaling during osteoclast differentiation. RANKL binding to LGR4 activates the Gαq and GSK3-β signaling pathway, an action that suppresses the expression and activity of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (NFATC1) during osteoclastogenesis. Both whole-body (Lgr4(-/-)) and monocyte conditional knockout mice of Lgr4 (Lgr4 CKO) exhibit osteoclast hyperactivation (including elevation of osteoclast number, surface area, and size) and increased bone erosion. The soluble LGR4 extracellular domain (ECD) binds RANKL and inhibits osteoclast differentiation in vivo. Moreover, LGR4-ECD therapeutically abrogated RANKL-induced bone loss in three mouse models of osteoporosis. Therefore, LGR4 acts as a second RANKL receptor that negatively regulates osteoclast differentiation and bone resorption.
We comment the recent paper which reported a series of TPA derivatives to show acid-induced tunable white light emission.
Display omitted We comment the recent paper which reported a series of TPA ...derivatives to show acid-induced tunable white light emission.
Visualization of biological targets such as crucial cells and biomolecules in living subjects is critical for the studies of important biological processes. Though 1H magnetic resonance imaging (MRI) ...has demonstrated its power in offering detailed anatomical and pathological information, its capacity for in vivo tracking of biological targets is limited by the high biological background of 1H. 19F distinguishes itself from its competitors as an exceptional complement to 1H in MRI through its high sensitivity, low biological background, and broad chemical shift range. The specificity and sensitivity of 19F MRI can be further boosted with activatable nanoprobes. The advantages of 19F MRI with activatable nanoprobes enable in vivo detection and imaging at the cellular or even molecular level in deep tissues, rendering this technique appealing as a potential solution for visualization of biological targets in living subjects. Here, recent progress over the past decades on activatable 19F MRI nanoprobes made from three major 19F‐containing compounds, as well as present challenges and potential opportunities, are summarized to provide a panoramic prospective for the people who are interested in this emerging and exciting field.
19F magnetic resonance imaging (MRI) with activatable nanoprobes enables real‐time, deep‐tissue, and background‐free imaging of cells and biomolecules in living subjects. Recent progress on activatable 19F MRI nanoprobes made from three major 19F‐containing compounds as well as present challenges and potential opportunities are discussed, giving more insights into activatable probe design for this emerging and encouraging field.
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