Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

<p>Abstract</p> <p>Background</p> <p>The nonstructural protein 1 (NSP1) of rotavirus has been reported to block interferon (IFN) signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs) and (or) the β-transducin repeat containing protein (β-TrCP). However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms.</p> <p>Results</p> <p>The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s) other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I), but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS), indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way.</p> <p>Conclusions</p> <p>Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.</p

Polymorphisms of the _ENPP1_ gene are not associated with type 2 diabetes or obesity in the Chinese Han population

*Objective:* Type 2 Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and with a major feature of insulin resistance. Genetic association studies have suggested that _ENPP1_ might play a potential role in susceptibility to type 2 diabetes and obesity. Our study aimed to examine the association between _ENPP1_ and type 2 diabetes and obesity.&#xd;&#xa;&#xd;&#xa;*Design:* Association study between two SNPs, rs1044498 (K121Q) and rs7754561 of ENPP1 and diabetes and obesity in the Chinese Han population.&#xd;&#xa;&#xd;&#xa;*Subjects:* 1912 unrelated patients (785 male and 1127 female with a mean age 63.8 &#xb1; 9 years), 236 IFG/IGT subjects (83 male and 153 female with a mean age 64 &#xb1; 9 years) and 2041 controls (635 male and 1406 female with a mean age 58 &#xb1; 9 years).&#xd;&#xa; &#xd;&#xa;*Measurements:* Subjects were genotyped for two SNPs using TaqMan technology on an ABI7900 system and tested by regression analysis.&#xd;&#xa;&#xd;&#xa;*Results:* By logistic regression analysis, rs1044498 (K121Q) and rs7754561 showed no statistical association with type 2 diabetes, obesity under additive, dominant and recessive models either before or after adjusting for sex and age. Haplotype analysis found a marginal association of haplotype C-G (p=0.05) which was reported in the previous study.&#xd;&#xa;&#xd;&#xa;*Conclusion:* Our investigation did not replicated the positive association found previously and suggested that the polymorphisms of _ENPP1_ might not play a major role in the susceptibility to type 2 diabetes or obesity in the Chinese Han population

A Thiazole Orange Derivative Targeting the Bacterial Protein FtsZ Shows Potent Antibacterial Activity.

The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli. The in vitro and in vivo results suggested that this compound disrupts the dynamic assembly of FtsZ protein and Z-ring formation through stimulating FtsZ polymerization. Moreover, this compound exhibits no activity on mammalian tubulin polymerization and shows low cytotoxicity on mammalian cells. Taken together, these findings could provide a new chemotype for development of antibacterials with FtsZ as the target

RFormer: Transformer-based Generative Adversarial Network for Real Fundus Image Restoration on A New Clinical Benchmark

Ophthalmologists have used fundus images to screen and diagnose eye diseases. However, different equipments and ophthalmologists pose large variations to the quality of fundus images. Low-quality (LQ) degraded fundus images easily lead to uncertainty in clinical screening and generally increase the risk of misdiagnosis. Thus, real fundus image restoration is worth studying. Unfortunately, real clinical benchmark has not been explored for this task so far. In this paper, we investigate the real clinical fundus image restoration problem. Firstly, We establish a clinical dataset, Real Fundus (RF), including 120 low- and high-quality (HQ) image pairs. Then we propose a novel Transformer-based Generative Adversarial Network (RFormer) to restore the real degradation of clinical fundus images. The key component in our network is the Window-based Self-Attention Block (WSAB) which captures non-local self-similarity and long-range dependencies. To produce more visually pleasant results, a Transformer-based discriminator is introduced. Extensive experiments on our clinical benchmark show that the proposed RFormer significantly outperforms the state-of-the-art (SOTA) methods. In addition, experiments of downstream tasks such as vessel segmentation and optic disc/cup detection demonstrate that our proposed RFormer benefits clinical fundus image analysis and applications. The dataset, code, and models are publicly available at https://github.com/dengzhuo-AI/Real-FundusComment: IEEE J-BHI 2022; The First Benchmark and First Transformer-based Method for Real Clinical Fundus Image Restoratio

Symmetry-breaking-induced nonlinear optics at a microcavity surface

Second-order nonlinear optical processes lie at the heart of many applications in both classical and quantum regimes1,2,3. Inversion symmetry, however, rules out the second-order nonlinear electric-dipole response in materials widely adopted in integrated photonics (for example, SiO_2, Si and Si_3N_4). Here, we report nonlinear optics induced by symmetry breaking at the surface of an ultrahigh-Q silica microcavity under a sub-milliwatt continuous-wave pump. By dynamically coordinating the double-resonance phase matching, a second harmonic is achieved with an unprecedented conversion efficiency of 0.049% W^(−1), 14 orders of magnitude higher than that of the non-enhancement case. In addition, the nonlinear effect from the intrinsic symmetry breaking at the surface can be identified unambiguously, with guided control of the pump polarization and the recognition of the second-harmonic mode distribution. This work not only extends the emission frequency range of silica photonic devices, but also lays the groundwork for applications in ultra-sensitive surface analysis

Enhanced Piezo-Photocatalytic Performance of Na₀.₅Bi₄.₅Ti₄O₁₅ by High-Voltage Poling

The internal electric field within a piezoelectric material can effectively inhibit the recombination of photogenerated electron–hole pairs, thus serving as a means to enhance photocatalytic efficiency. Herein, we synthesized a Na₀.₅Bi₄.₅Ti₄O₁₅ (NBT) catalyst by the hydrothermal method and optimized its catalytic performance by simple high-voltage poling. When applying light and mechanical stirring on a 2 kV mm⁻¹ poled NBT sample, almost 100% of Rhodamine B solution could be degraded in 120 min, and the reaction rate constant reached as high as 28.36 × 10⁻³ min⁻¹, which was 4.2 times higher than that of the unpoled NBT sample. The enhanced piezo-photocatalytic activity is attributed to the poling-enhanced internal electric field, which facilitates the efficient separation and transfer of photogenerated carriers. Our work provides a new option and idea for the development of piezo-photocatalysts for environmental remediation and pollutant treatment