A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling.

Interferons (IFNs) induce an antimicrobial state, protecting tissues from infection. Many viruses inhibit IFN signaling, but whether bacterial pathogens evade IFN responses remains unclear. Here, we demonstrate that the Shigella OspC family of type-III-secreted effectors blocks IFN signaling independently of its cell death inhibitory activity. Rather, IFN inhibition was mediated by the binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II and downstream JAK/STAT signaling. The growth of Shigella lacking OspC1 and OspC3 was attenuated in epithelial cells and in a murine model of infection. This phenotype was rescued in both models by the depletion of IFN receptors. OspC homologs conserved in additional pathogens not only bound CaM but also inhibited IFN, suggesting a widespread virulence strategy. These findings reveal a conserved but previously undescribed molecular mechanism of IFN inhibition and demonstrate the critical role of Ca2+ and IFN targeting in bacterial pathogenesis.

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum levels of fibroblast growth factor 21 (FGF21) are associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. The present study evaluated the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD. METHODS: We included patients undergoing MHD using AVF from January 2018 to December 2019. FGF21 concentration was detected using enzyme-linked immunosorbent assay. Patients were followed up to record two clinical outcomes, AVF functional patency loss and all-cause mortality. The follow-up period ended on April 30, 2022. RESULTS: Among 147 patients, the mean age was 58.49 ± 14.41 years, and the median serum level of FGF21 was 150.15 (70.57-318.01) pg/mL. During the median follow-up period of 40.83 months, the serum level of FGF21 was an independent risk factor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001-1.003, p = 0.003]). Patients with higher serum levels of FGF21 were more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000-1.003, p = 0.014]). The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/mL and 146.43 pg/mL, with AUCs of 0.701 (95% CI: 0.606-0.796, p < 0.001) and 0.677 (95% CI: 0.595-0.752, p = 0.002), respectively. CONCLUSIONS: Serum FGF21 levels were an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.

Total synthesis of (±)-mersicarpine following a 6-exo-trig radical cyclization.

Described is a total synthesis of racemic mersicarpine from diethyl 4-oxopimelate. The synthetic route takes advantage of a 2-indolyl radical cyclization to construct the pyrido[1,2-a]indole scaffold bearing the all-carbon quaternary stereocenter.

Design of mmWave Directional Antenna for Enhanced 5G Broadcasting Coverage.

5G mmWave broadcasting is considered to be the main method of future broadcasting. However, the mmWave transmission has a large space loss, especially in tunnels. In order to compensate for the attenuation of the broadcast signal, a directional horn antenna is designed in this paper. Substrate integrated waveguide (SIW) technology, dual-element arrays and extension structures are used to improve the antenna structure and achieve good directional characteristics. The multi-objective genetic algorithm (MOGA) is used to optimize the antenna parameters and improve optimization efficiency. Ultimately, the whole antenna was 28.2 mm in length and 28.6 mm in width, and the FR4 material, with a relative permittivity of 4.4, was used as a dielectric plate. The maximum gain of the antenna is 8.06 dB, and the bandwidth with gain greater than 6.5 dB is nearly 2 GHz. Antenna performance simulation and test results show that the extended semicircular structure is beneficial in enhancing the directional radiation of the antenna. This provides a reference method for directional antennas applied to 5G millimeter wave bands to increase gain and narrow beams.

Self-Assembled Colloidal Particle Clusters from In Situ Pickering-Like Emulsion Polymerization via Single Electron Transfer Mechanism.

A simple route is reported to synthesize colloidal particle clusters (CPCs) from self-assembly of in situ poly(vinylidene fluoride)/poly(styrene-co-tert-butyl acrylate) [PVDF/P(St-co-tBA)] Janus particles through one-pot seeded emulsion single electron transfer radical polymerization. In the in situ Pickering-like emulsion polymerization, the tBA/St/PVDF feed ratio and polymerization temperature are important for the formation of well-defined CPCs. When the tBA/St/PVDF feed ratio is 0.75 g/2.5 g/0.5 g and the reaction temperature is 35 °C, relatively uniform raspberry-like CPCs are obtained. The hydrophobicity of the P(St-co-tBA) domains and the affinity of PVDF to the aqueous environment are considered to be the driving force for the self-assembly of the in situ formed PVDF/P(St-co-tBA) Janus particles. The resultant raspberry-like CPCs with PVDF particles protruding outward may be promising for superhydrophobic smart coatings.

The nonstructural protein 1 of respiratory syncytial virus hijacks host mitophagy as a novel mitophagy receptor to evade the type I IFN response in HEp-2 cells.

Mitochondria are good targets for viruses to manipulate their hosts. However, it remains obscure whether respiratory syncytial virus (RSV) target mitochondria to suppress the type I interferon (IFN) responses. Here, we show that nonstructural protein 1 (NS1) protein of RSV interacts with Tu translation elongation factor mitochondrial (TUFM), which can lead to its localization in mitochondria and finally induce TUFM-dependent mitophagy and inhibition of IFNß. Mechanically, NS1-mediated TUFM-dependent mitophagy does not depend on the PINK1-PARKIN pathway and classic mitophagy receptors. Importantly, NS1 may act as a new receptor protein to bridge mitochondria and autophagosomes by interacting with TUFM and LC3B. The LIR motif of NS1 protein is essential for its interaction with LC3B and is of great importance for its mitophagy induction and IFNß suppression. Finally, NS1-induced TUFM-dependent mitophagy was essential for its attenuated IFNß response using autophagy-deficient cells and mice. Our study provides a novel mitophagy receptor molecular and a new antiviral option by suppressing antiviral innate immune via targeting TUFM-dependent mitophagy. IMPORTANCE It is a worthy concern for us to understand virus-host interactions which affect progression and prognosis of disease. We demonstrated that the non-structural protein 1 of respiratory syncytial virus (RSV NS1) may act as a novel mitophagy receptor to induce mitophagy by binding LC3B and mitochondrial protein TUFM, and finally dampen interferon (IFN) responses induced by RIG1 and RSV infection. TUFM is beneficial for RSV replication in vivo and vitro. It is new and interesting that RSV NS1 may function as a mitophagy receptor to interact with LC3B. The LIR motif of NS1 protein is essential for its interaction with LC3B. We further confirm that RSV NS1 inhibited IFNß response and promoted RSV replication in autophagy-dependent mechanisms in vivo and vitro. Our study contributes to understanding virus-host interaction, enriching our insights into RSV pathogenic mechanism and exploiting new antiviral treatments targeting TUFM.

Are people willing to buy natural disaster insurance in China? Risk awareness, insurance acceptance, and willingness to pay.

After the Wenchuan earthquake (magnitude 7.9, May 12, 2008), intensive debates on how China should establish a natural disaster insurance system were initiated among researchers, policymakers, and insurance professionals. Our focus was the social aspects of disaster insurance, explored in China through a nationwide survey. Our questionnaires investigated people's risk awareness, insurance acceptance, their opinions on governmental measures for disaster management, and their willingness to pay for disaster house insurance. We analyzed the results at both regional and individual scales. We found that the integrated hazard index and respondents' experience of insurance (considered objective factors), and their opinions on the importance of insurance and government responsibility (considered subjective factors) showed strong correlation with the regional overall acceptance of disaster insurance. An individual's decision to participate highly depended on his/her experience of both insurance and disaster and his/her opinion on the importance of insurance as a coping mechanism. Respondents from poverty-stricken or less-developed counties were not necessarily more reluctant to accept natural disaster insurance, though they exhibited relatively lower ability to afford insurance. In general, respondents had correct perceptions of natural disasters in their areas; however, people from regions with a greater multihazard threat showed less willingness to accept disaster insurance because they tended to expect the government to undertake to cover losses and considered insurance to be less important. People's willingness to pay for an assumed disaster house insurance was also investigated and analyzed. We consequently discuss the policy implications for developing a disaster insurance system in China.