Abstract
We report the observations of FRB 20220912A using the Five-hundred-meter Aperture Spherical radio Telescope. We conducted 17 observations totaling 8.67 hr and detected a total of 1076 bursts ...with an event rate up to 390 hr
−1
. The cumulative energy distribution can be well described using a broken power-law function with the lower- and higher-energy slopes of −0.38 ± 0.02 and −2.07 ± 0.07, respectively. We also report the
L
-band (1–1.5 GHz) spectral index of the synthetic spectrum of FRB 20220912A bursts, which is −2.6 ± 0.21. The average rotation measure value of the bursts from FRB 20220912A is −0.08 ± 5.39 rad m
−2
, close to 0 rad m
−2
and was relatively stable over 2 months. Most bursts have nearly 100% linear polarization. About 45% of the bursts have circular polarization with Signal-to-Noise ratio > 3, and the highest circular polarization degree can reach 70%. Our observations suggest that FRB 20220912A is located in a relatively clean local environment with complex circular polarization characteristics. These various behaviors imply that the mechanism of circular polarization of FRBs likely originates from an intrinsic radiation mechanism, such as coherent curvature radiation or inverse Compton scattering inside the magnetosphere of the FRB engine source (e.g., a magnetar).
Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate ...antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate antiviral immune response. How the binding of viral RNA to and activation of the RLRs are ...regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co-receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune response to RNA virus.
•ZCCHC3 mediates viral RNA-triggered innate immune response•ZCCHC3 binds to viral RNA•ZCCHC3 acts as a co-receptor for RIG-I and MDA5•ZCCHC3 mediates polyubiquitination and activation of RIG-I and MDA5 by TRIM25
Recognition of viral RNA by RIG-I-like receptors (RLRs) initiates innate antiviral response. Lian et al. demonstrate that ZCCHC3 is a co-receptor for RLRs, thereby acting as an important modulator of innate antiviral response.
Metal binding to microbial extracellular polymeric substances (EPS) greatly influences the distribution of heavy metals in microbial aggregates, soil and aquatic systems in nature. In this work, the ...thermodynamic characteristics of the binding between aqueous metals (with copper ion as an example) and EPS of activated sludge were investigated. Isothermal titration calorimetry was employed to estimate the thermodynamic parameters for the binding of Cu2+ onto EPS, while three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy with parallel factor analysis was used for quantifying the complexation of Cu2+ with the EPS. The binding mechanisms were further explored by X-ray absorption fine structure (XAFS) and Fourier transform infrared (FTIR) spectroscopy analysis. The results show that the proteins and humic substances in EPS were both strong ligands for Cu2+. The binding capacity N, binding constant K, binding enthalpy ΔH were calculated as 5.74 × 10−2 mmol/g, 2.18 × 105 L/mol, and −11.30 kJ/mol, respectively, implying that such a binding process was exothermic and thermodynamically favorable. The binding process was found to be driven mainly by the entropy change of the reaction. A further investigation shows that Cu2+ bound with the oxygen atom in the carboxyl groups in the EPS molecules of activated sludge. This study facilitates a better understanding about the roles of EPS in protecting microbes against heavy metals.
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► Thermodynamic characteristics of binding of Cu2+ to EPS are investigated. ► The binding process is exothermic and thermodynamically favorable. ► Cu2+ binds with the O atom in the carboxyl groups in EPS.
Cancer incidence is rising, and the efficacy of current available anticancer agents is limited by severe dose‐limiting toxicities and drug resistance problems. Nanoparticles are heralded as the next ...frontier in cancer treatment. Here, a pure physical method is used to efficiently fabricate very small silver particles even approaching the Ångstrom (Ång) dimension. Fructose is used as a dispersant and stabilizer to coat the Ång‐scale silver particles (AgÅPs). Functional and mechanistic studies demonstrate that fructose‐coated AgÅPs (F‐AgÅPs) can enter and accumulate in multiple cultured cancer cell lines to induce apoptotic death, whereas most normal cells are resistant to the efficacious dose of F‐AgÅPs; in vivo, intravenous administration of F‐AgÅPs potently inhibits the growth of pancreatic and lung cancer xenografts in nude mice, without inducing notable toxic effects on the healthy tissues. The results suggest the promising potential of F‐AgÅPs as a potent, safe, and broad‐spectrum agent for the cancer treatment.
Physical method‐fabricated fructose‐coated Ångstrom‐scale silver particles (F‐AgÅPs) have the ability to enter multiple cancer cells to induce apoptosis. Intravenous injection of F‐AgÅPs potently inhibits the growth of cancer xenograft models, without inducing notable toxic effects on healthy tissues. These results suggest that F‐AgÅPs have a great potential to be used as a potent, safe, and broad‐spectrum agent for cancer treatment.
Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
The changeable molecular dynamics of flexible polar cations in the variable confined space between inorganic chains brings about a new type of two‐step nonlinear optical (NLO) switch with genuine ...“off–on–off” second harmonic generation (SHG) conversion between one NLO‐active state and two NLO‐inactive states.
Strength and toughness are usually mutually exclusive for materials. The sacrificial bond strategy is used to address the trade‐off between strength and toughness. However, the complex construction ...process of sacrificial network limits the application of sacrificial network. This work develops a facile strategy to construct an interfacial interactions‐driven sacrificial network. The authors' group finds that there are the interfacial interactions between arginines (A) aggregates and molecular chains. Such interfacial interactions result in the mechanical properties of samples having a strong dependence on extension rates, which shows that A aggregates construct a network structure by interfacial interactions. The interfacial interactions between A aggregates and chains improve the strength of samples; while the A aggregate network driven by interfacial interactions preferentially ruptures to dissipate large energy for the improvement of fracture toughness, which can be considered as a sacrificial network. Therefore, their designed elastomers have both high strength and high toughness. This work provides an easier strategy for the construction of sacrificial networks, which can promote the industrial application of sacrificial networks in elastomer materials.
Through the interfacial interactions, an amino acid aggregate network forms. This work provides an easier strategy for the construction of sacrificial networks, which can promote the industrial application of sacrificial networks in elastomer materials.
Mediator of IRF3 activation (MITA, also known as stimulator of interferon genes, STING) senses the second messenger cyclic GMP-AMP (cGAMP) which is synthesized upon DNA virus infection and activates ...innate antiviral immune response. It has been demonstrated that the activity of MITA is delicately regulated by various post-translational modifications including polyubiquitination. In this study, we identified the deubiquitinating enzyme USP44 as a positive regulator of MITA. USP44 is recruited to MITA following DNA virus infection and removes K48-linked polyubiquitin moieties from MITA at K236, therefore prevents MITA from proteasome mediated degradation. USP44-deficiency results in acceleration of HSV-1-induced degradation of MITA and reduced induction of type I interferons (IFNs) and proinflammatory cytokines. Consistently, Usp44-/- mice are more susceptible to HSV-1 infection as indicated by higher tissue viral titers, greater tissue damage and lower survival rate. These findings suggest that USP44 plays a specific and critical role in the regulation of innate immune response against DNA viruses.
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