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"Lin, Hongyu"
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The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response
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.
RIG-I is an RNA sensor and is required for effective antiviral immunity. Cao and colleagues demonstrate that the previously undescribed long noncoding RNA Lnczc3h7a serves an essential scaffolding role in supporting productive RIG-I signaling.
Journal Article
Super-multiplexed imaging and coding in the range of radio frequency
The era of the Internet has led to an information explosion, creating significant challenges for current techniques in information storage and access. High-performance strategies that expand existing methods offer a promising solution. Imaging-based approaches are vital for information perception but remain underexplored for information processing due to limited multiplexity. Here, we introduce
19
F magnetic resonance imaging-Empowered information Assess and Storage Technique (FEAST), enabled by 22 fluorinated quaternary ammonium derivatives with distinct
19
F chemical shifts. We developed three coding platforms for FEAST: fluorinated choline analog solutions, fluorinated deep eutectic solvents, and fluorinated ionogels. These platforms allow 2-spatial-dimensional applications, such as 16-bit encoding, “dual-color” watermarking, multiplexed Colorcodes, and encrypted QR codes, as well as 3-spatial-dimensional applications like “cubic” information storage, implanted anti-counterfeit labels, and FEAST-guided encryption. This work highlights FEAST’s potential for advanced information storage and access, which is inspiring for further developments with versatile and robust coding platforms.
Imaging-based approaches have potential in information storage but achieving the required multiplexity can be challenging. Here, the authors report the development of an MRI-based technique using 22 fluorinated quaternary ammonium derivatives with distinct
19
F chemical shifts.
Journal Article
Prognostic effect of osteoprotegerin in patients with ischemic stroke: A systematic review and meta-analysis
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.
Journal Article
Spatial temporal trends and inequality in agricultural eco-efficiency under carbon constraints in China
Eco-efficiency in cultivated land use is crucial for ensuring food security and promoting sustainable agriculture amidst the challenges posed by urbanization and climate change. Distinct from much of the existing literature, this paper adopts a super-efficiency EBM model that integrates both radial and non-radial perspectives to estimate the eco-efficiency of cultivated land use and identify sources of inefficiency under carbon emission constraints, focusing on 180 prefecture-level cities in China’s major grain-producing regions. Additionally, spatial kernel density estimation is applied to analyze the spatiotemporal dynamics and long-term trends in eco-efficiency, while the Dagum Gini coefficient is used to examine the causes of spatiotemporal disparities. The key findings include (1) The Songhua River Basin shows significantly higher eco-efficiency (mean: 0.718) than the Yellow River (mean: 0.559) and Yangtze River Basins (mean: 0.587), with distinct evolutionary patterns; (2) Long-term evolution reflects a bipolar pattern with spatial agglomeration disparities; (3) Positive spatial spillover effects are evident in regions with efficiency levels between 0.4 and 0.9, with inter-regional differences and super-variable density as significant spatial variation sources. This study reveals a “long-term increase - short-term decline” trend in ecological efficiency, highlighting carbon emissions as the primary limiting factor, although this constraint is gradually diminishing.
Journal Article
Association between inflammation indicators and albuminuria in US adults: a cross-sectional study
Previous studies have established associations between the C-reactive protein to lymphocyte ratio (CLR), inflammatory load index (IBI), and neutrophil to albumin ratio (NAR) with various conditions. However, the evidence for such associations in individuals with albuminuria remains unclear. This study aimed to investigate the relationship between inflammatory biomarkers and the presence of albuminuria by utilizing data derived from the National Health and Nutrition Examination Survey (NHANES). Participants were classified into two groups according to their urinary albumin-to-creatinine ratio (UACR): those who presented with albuminuria and those who did not. The association between inflammatory biomarkers and the occurrence of albuminuria was assessed through multivariate regression models. To explore possible non-linear relationships, restricted cubic spline (RCS) analysis was applied. Furthermore, subgroup and sensitivity analyses were conducted to ensure the reliability and consistency of the findings. The study included 18,876 participants, of whom 2,321 were classified in the albuminuria group and 16,555 in the non-albuminuria group. The results from a fully adjusted logistic regression model indicated a significant positive relationship between the natural logarithm-transformed inflammatory markers—Ln-CLR, Ln-IBI, and Ln-NAR—and the risk of presence albuminuria. Specifically, each unit increase in Ln-CLR, Ln-IBI, and Ln-NAR was linked with a 12%, 15%, and 79% heightened risk of albuminuria, respectively. RCS analysis showed a linear relationship between Ln-CLR, Ln-IBI and Ln-NAR and albuminuria. Subgroup analyses demonstrated consistent findings across various populations, and numerous sensitivity tests confirmed the reliability of these outcomes. This study demonstrates a positive correlation between CLR, IBI, and NAR and the presence albuminuria in US adults. Given these results, early monitoring of these inflammatory markers in high-risk populations is essential for identifying the onset of albuminuria and mitigating kidney damage progression.
Journal Article
LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption
LGR4 has been identified as a new receptor for RANKL in bone cells where it opposes RANK signaling to inhibit osteoclasts differentiation, and its therapeutic targeting promotes reduced bone loss in three mouse models of osteoporosis.
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 Gα
q
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.
Journal Article
Volcanic history of the Imbrium basin
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.
Journal Article
Ash1l and lnc-Smad3 coordinate Smad3 locus accessibility to modulate iTreg polarization and T cell autoimmunity
Regulatory T (Treg) cells are important for the maintenance of immune homoeostasis and prevention of autoimmune diseases. Epigenetic modifications have been reported to modulate autoimmunity by altering Treg cell fate. Here we show that the H3K4 methyltransferase Ash1l facilitates TGF-β-induced Treg cell polarization
in vitro
and protects mice from T cell-mediated colitis
in vivo
. Ash1l upregulates Smad3 expression by directly targeting
Smad3
promoter to increase local H3K4 trimethylation. Furthermore, we identify an lncRNA, namely lnc-Smad3, which interacts with the histone deacetylase HDAC1 and silences Smad3 transcription. After TGF-β stimulation, activated Smad3 suppresses lnc-Smad3 transcription, thereby recovering the
Smad3
promoter accessibility to Ash1l. By revealing the opposite regulatory functions of Ash1l and lnc-Smad3 in Smad3 expression, our data provide insights for the epigenetic control of Treg cell fate to potentially aid in the development of therapeutic intervention for autoimmune diseases.
The transcriptional program activated by Smad2/Smad3 is critical for the induction and function of regulatory T cells. Here the authors show that the expression of Smad3 is modulated by the complementary functions of a methyltransferase Ash1l and an lncRNA lnc-Smad3 on the promoter accessibility of the mouse
Smad3
locus.
Journal Article
Novel Pectic Polysaccharides Isolated from Immature Honey Pomelo Fruit with High Immunomodulatory Activity
A novel pectic polysaccharide (HPP-1) with high immunomodulatory activity was extracted and isolated from the immature honey pomelo fruit (Citrus grandis). Characterization of its chemical structure indicated that HPP-1 had a molecular weight of 59,024 D. In addition, HPP-1 was primarily composed of rhamnose, arabinose, fucose, mannose, and galactose at a molar ratio of 1.00:11.12:2.26:0.56:6.40. Fourier-transform infrared spectroscopy, periodic acid oxidation, and Smith degradation results showed that HPP-1 had α- and β-glycosidic linkages and 1 → 2, 1 → 4, 1 → 6, and 1 → 3 glycosidic bonds. 13C NMR and 1H NMR analyses revealed that the main glycogroups included 1,4-D-GalA, 1,6-β-D-Gal, 1,6-β-D-Man, 1,3-α-L-Ara, and 1,2-α-L-Rha. Immunomodulatory bioactivity analysis using a macrophage RAW264.7 model in vitro revealed that NO, TNF-α, and IL-6 secretions were all considerably increased by HPP-1. Moreover, RT-PCR results showed that HPP-1-induced iNOS, TNF-α, and IL-6 expression was significantly increased in macrophages. HPP-1-mediated activation in macrophages was due to the stimulation of the NF-κB and MAPK signaling pathways based on western blot analyses. HPP-1 extracted from immature honey pomelo fruit has potential applications as an immunomodulatory supplement.
Journal Article