MnFe Prussian Blue Analogue Open Cages for Sodium-Ion Batteries: Simultaneous Evolution of Structure, Morphology, and Energy Storage Properties.

Prussian blue analogues (PBAs) exhibiting hollow morphologies have garnered considerable attention owing to their remarkable electrochemical properties. In this study, a one-pot strategy is proposed for the synthesis of MnFe PBA open cages. The materials are subsequently employed as cathode electrode in sodium-ion batteries (SIBs). The simultaneous evolution of structure, morphology, and performance during the synthesis process is investigated. The findings reveal substantial structural modifications as the reaction time is prolonged. The manganese content in the samples diminishes considerably, while the potassium content experiences an increase. This compositional variation is accompanied by a significant change in the spin state of the transition metal ions. These structural transformations trigger the occurrence of the Kirkendall effect and Oswald ripening, culminating in a profound alteration of the morphology of MnFe PBA. Moreover, the shifts in spin states give rise to distinct changes in their charge-discharge profiles and redox potentials. Furthermore, an exploration of the formation conditions of the samples and their variations before and after cycling is conducted. This study offers valuable insights into the intricate relationship between the structure, morphology, and electrochemical performance of MnFe PBA, paving the way for further optimizations in this promising class of materials for energy storage applications.

High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis.

BACKGROUND: The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein. METHODS: C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined. RESULTS: HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells. CONCLUSIONS: This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.

Nonstructural Protein NSs Activates Inflammasome and Pyroptosis through Interaction with NLRP3 in Human Microglial Cells Infected with Severe Fever with Thrombocytopenia Syndrome Bandavirus.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1ß (IL-1ß) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1ß and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1ß secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.

Ionic COF Composite Membranes for Selective Perfluoroalkyl Substances Separation.

High-performance membranes are critical to membrane separation technology. In recent years, 2D covalent organic frameworks (2D COFs) have attracted extensive attention in the field of membrane separation due to their high porosity, ordered channels, and fine-tuned pore sizes, which are considered as excellent candidate to solve the trade-off between membrane selectivity and permeability. Herein, two kinds of ionic 2D COFs with different charge properties (termed as iCOFs) are integrated into polyacrylonitrile (PAN) substrates to form two composite membranes (PAN@iCOFs) with excellent selective perfluoroalkyl substances (PFASs) separation performance with high solvent permeability and good mechanical properties. The as-prepared PAN@iCOFs composite membranes can selectively reject more than 99.0% of positively and negatively charged PFASs in wastewater while maintaining good stability and recyclability.

Phosphoinositide 3-kinase/Akt and its related signaling pathways in the regulation of tumor-associated macrophages polarization.

Tumor-associated macrophages (TAMs) are a type of functionally plastic immune cell population in tumor microenvironment (TME) and mainly polarized into two phenotypes: M2 and M1-like TAMs. The M2-like TAMs could stimulate tumor growth and metastasis, tissue remodeling and immune-suppression, whereas M1-like TAMs could initiate immune response to dampen tumor progression. TAMs with different polarization phenotypes can produce various kinds of cytokines, chemokines and growth factors to regulate immunity and inflammatory responses. It is an effective method to treat cancer through ameliorating TME and modulating TAMs by converting M2 into M1-like phenotype. However, intracellular signaling mechanisms underlying TAMs polarization are largely undefined. Phosphoinositide 3-kinase (PI3K)/Akt is an important signaling pathway participating in M2-like TAMs polarization, survival, growth, proliferation, differentiation, apoptosis and cytoskeleton rearrangement. In the present review, we analyzed the mechanism of TAMs polarization focusing on PI3K/Akt and its downstream mitogen­activated protein kinase (MAPK) as well as nuclear factor kappa B (NF-κB) signaling pathways, thus provides the first evidence of intracellular targets for cancer immunotherapy.

DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation.

G-quadruplexes (G4) are noncanonical secondary structures formed in guanine-rich DNA and RNA sequences. MYC, one of the most critical oncogenes, forms a DNA G4 in its proximal promoter region (MycG4) that functions as a transcriptional silencer. However, MycG4 is highly stable in vitro and its regulatory role would require active unfolding. Here we report that DDX5, one of the founding members of the DEAD-box RNA helicase family, is extremely proficient at unfolding MycG4-DNA. Our results show that DDX5 is a highly active G4-resolvase that does not require a single-stranded overhang and that ATP hydrolysis is not directly coupled to G4-unfolding of DDX5. The chromatin binding sites of DDX5 are G-rich sequences. In cancer cells, DDX5 is enriched at the MYC promoter and activates MYC transcription. The DDX5 interaction with the MYC promoter and DDX5-mediated MYC activation is inhibited by G4-interactive small molecules. Our results uncover a function of DDX5 in resolving DNA and RNA G4s and suggest a molecular target to suppress MYC for cancer intervention.

The RNA helicase DDX5 supports mitochondrial function in small cell lung cancer.

DEAD-box helicase 5 (DDX5) is a founding member of the DEAD-box RNA helicase family, a group of enzymes that regulate ribonucleoprotein formation and function in every aspect of RNA metabolism, ranging from synthesis to decay. Our laboratory previously found that DDX5 is involved in energy homeostasis, a process that is altered in many cancers. Small cell lung cancer (SCLC) is an understudied cancer type for which effective treatments are currently unavailable. Using an array of methods, including short hairpin RNA-mediated gene silencing, RNA and ChIP sequencing analyses, and metabolite profiling, we show here that DDX5 is overexpressed in SCLC cell lines and that its down-regulation results in various metabolic and cellular alterations. Depletion of DDX5 resulted in reduced growth and mitochondrial dysfunction in the chemoresistant SCLC cell line H69AR. The latter was evidenced by down-regulation of genes involved in oxidative phosphorylation and by impaired oxygen consumption. Interestingly, DDX5 depletion specifically reduced intracellular succinate, a TCA cycle intermediate that serves as a direct electron donor to mitochondrial complex II. We propose that the oncogenic role of DDX5, at least in part, manifests as up-regulation of respiration supporting the energy demands of cancer cells.

Suppression of the IFN-α and -ß Induction through Sequestering IRF7 into Viral Inclusion Bodies by Nonstructural Protein NSs in Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection.

Induction of type I IFNs during viral infection is crucial for host defense. IRF 3 and IRF7 play a critical role as key transcription factors in the activation of the IFN induction. Viruses have evolved a variety of strategies to evade innate immunity. Our previous studies have shown that the nonstructural protein (NSs) of the severe fever with thrombocytopenia syndrome virus (SFTSV) can suppress the IFN-ß induction through its interaction with tank-binding kinase-1 and sequestering the inhibitor of nuclear factor kappa B kinase(IKK) complex into the inclusion bodies formed by NSs. In this study, we characterized the unique function of IRF7 in innate immunity and its role in inducing IFN-α in particular, regulated by NSs during the SFTSV infection in several cell types of human origin. Whereas IRF3 is constitutively expressed, IRF7 was significantly induced differentially in various cell types in response to SFTSV infection, promoted the induction of IFN-α2 and -α4, and further induced IFN-ß, thus contributing to suppressing the viral replication. Our data indicate that NSs directly interacted with and sequestered IRF7 into the inclusion bodies, which is different from IRF3 indirectly interacting with NSs. Although interaction of NSs with IRF7 did not inhibit IRF7 phosphorylation, p-IRF7 was trapped in the inclusion bodies, resulting in a significant reduction of the IFN-α2 and -α4 induction and therefore enhanced viral replication. Interaction of the viral NSs with both IRF7 and IRF3 and subsequent sequestration of these transcription factors into viral inclusion bodies, a unique strategy used by this phlebovirus, may ensure effective evasion and suppression of host innate immunity.

Photoinduced Self-Assembly of Carbon Nitride Quantum Dots.

The study of nanocrystal self-assembly into superlattices or superstructures is of great significance in nanoscience. Carbon nitride quantum dots (CNQDs), being a promising new group of nanomaterials, however, have hardly been explored in their self-organizing behavior. Here we report of a unique irradiation-triggered self-assembly and recrystallization phenomenon of crystalline CNQDs (c-CNQDs) terminated by abundant oxygen-containing groups. Unlike the conventional self-assembly of nanocrystals into ordered superstructures, the photoinduced self-assembly of c-CNQDs resembles a "click reaction" process of macromolecules, in which the activated -OH and -NH2 functional groups along the perimeters initiate cross-linking of adjacent QDs through a photocatalytic effect. Our findings unveil fundamental physiochemical features of CNQDs and open up new possibilities of manipulating carbon nitride nanomaterials via controlled assembly. Prospects for potential applications are discussed as well.

Systematic analysis of the basic/helix-loop-helix (bHLH) transcription factor family in pummelo (Citrus grandis) and identification of the key members involved in the response to iron deficiency.

BACKGROUND: Iron (Fe) deficiency is a common problem in citrus production. As the second largest superfamily of transcription factors (TFs), the basic/helix-loop-helix (bHLH) proteins have been shown to participate in the regulation of Fe homeostasis and a series of other biological and developmental processes in plants. However, this family of members in citrus and their functions in citrus Fe deficiency are still largely unknown. RESULTS: In this study, we identified a total of 128 CgbHLHs from pummelo (Citrus grandis) genome that were classified into 18 subfamilies by phylogenetic comparison with Arabidopsis thaliana bHLH proteins. All of these CgbHLHs were randomly distributed on nine known (125 genes) and one unknown (3 genes) chromosomes, and 12 and 47 of them were identified to be tandem and segmental duplicated genes, respectively. Sequence analysis showed detailed characteristics of their intron-exon structures, bHLH domain and conserved motifs. Gene ontology (GO) analysis suggested that most of CgbHLHs were annotated to the nucleus, DNA-binding transcription factor activity, response to abiotic stimulus, reproduction, post-embryonic development, flower development and photosynthesis. In addition, 27 CgbHLH proteins were predicted to have direct or indirect protein-protein interactions. Based on GO annotation, RNA sequencing data in public database and qRT-PCR results, several of CgbHLHs were identified as the key candidates that respond to iron deficiency. CONCLUSIONS: In total, 128 CgbHLH proteins were identified from pummelo, and their detailed sequence and structure characteristics and putative functions were analyzed. This study provides comprehensive information for further functional elucidation of CgbHLH genes in citrus.

Evaluation of the Risk Prediction Tools for Patients With Coronavirus Disease 2019 in Wuhan, China: A Single-Centered, Retrospective, Observational Study.

OBJECTIVES: To evaluate and compare the efficacy of National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment on predicting in-hospital death in patients with coronavirus disease 2019. DESIGN: A retrospective, observational study. SETTING: Single center, West Campus of Wuhan Union hospital-a temporary center to manage critically ill patients with coronavirus disease 2019. PATIENTS: A total of 673 consecutive adult patients with coronavirus disease 2019 between January 30, 2020, and March 14, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demography, comorbidities, vital signs, mental status, oxygen saturation, and use of supplemental oxygen at admission to the ward were collected from medical records and used to score National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Total number of patients was 673 (51% male) and median (interquartile range) age was 61 years (50-69 yr). One-hundred twenty-one patients died (18%). For predicting in-hospital death, the area under the receiver operating characteristics (95% CI) for National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment were 0.882 (0.847-0.916), 0.880 (0.845-0.914), 0.839 (0.800-0.879), 0.766 (0.718-0.814), and 0.694 (0.641-0.746), respectively. Among the parameters of National Early Warning Score, the oxygen saturation score was found to be the most significant predictor of in-hospital death. The area under the receiver operating characteristic (95% CI) for oxygen saturation score was 0.875 (0.834-0.916). CONCLUSIONS: In this single-center study, the discrimination of National Early Warning Score/National Early Warning Score 2 for predicting mortality in patients with coronavirus disease 2019 admitted to the ward was found to be superior to Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Peripheral oxygen saturation could independently predict in-hospital death in these patients. Further validation of our finding in multiple settings is needed to determine its applicability for coronavirus disease 2019.

Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease.

Hydatidiform moles are classified at the genetic level as androgenetic complete mole and diandric-monogynic partial mole. Conflicting data exist whether heterozygous complete moles are more aggressive clinically than homozygous complete moles. We investigated clinical outcome in a large cohort of hydatidiform moles in Chinese patients with an emphasis on genotypical correlation with post-molar gestational trophoblastic disease. Consecutive products of conceptions undergoing DNA genotyping and p57 immunohistochemistry to rule out molar gestations were included from a 5-year period at Beijing Obstetrics and Gynecology Hospital. Patient demographics and clinical follow-up information were obtained. Post-molar gestational trophoblastic disease or gestational trophoblastic neoplasia was determined by the 2002 WHO/FIGO criteria. A total of 1245 products of conceptions were classified based on genotyping results into 219 complete moles, 250 partial moles, and 776 non-molar gestations. Among 219 complete moles, 186 were homozygous/monospermic and 33 were heterozygous/dispermic. Among 250 partial moles, 246 were triploid dispermic, 2 were triploid monospermic, and 2 were tetraploid heterozygous partial moles. Among 776 non-molar gestations, 644 were diploid without chromosomal aneuploidies detectable by STR genotyping and 132 had various genetic abnormalities including 122 cases of various trisomies, 2 triploid digynic-monoandric non-molar gestations, 7 cases of possible chromosomal monosomy or uniparental disomy. Successful follow-up was achieved in 165 complete moles: post-molar gestational trophoblastic disease developed in 11.6% (16/138 cases) of homozygous complete moles and 37.0% (10/27 cases) of heterozygous complete moles. The difference between the two groups was highly significant (p = 0.0009, chi-square). None of the 218 partial moles and 367 non-molar gestations developed post-molar gestational trophoblastic disease. In conclusion, heterozygous/dispermic complete moles are clinically more aggressive with a significantly higher risk for development of post-molar gestational trophoblastic disease compared with homozygous/monospermic complete moles. Therefore, precise genotyping classification of complete moles is important for clinical prognosis and patient management.

Comprehensive Analysis of Autophagy-Related Genes in Sweet Orange (Citrus sinensis) Highlights Their Roles in Response to Abiotic Stresses.

Autophagy is a highly conserved intracellular degradation pathway that breaks down damaged macromolecules and/or organelles. It is involved in plant development and senescence, as well as in biotic and abiotic stresses. However, the autophagy process and related genes are largely unknown in citrus. In this study, we identified 35 autophagy-related genes (CsATGs-autophagy-related genes (ATGs) of Citrus sinensis, Cs) in a genome-wide manner from sweet orange (Citrus sinensis). Bioinformatic analysis showed that these CsATGs were highly similar to Arabidopsis ATGs in both sequence and phylogeny. All the CsATGs were randomly distributed on nine known (28 genes) and one unknown (7 genes) chromosomes. Ten CsATGs were predicted to be segmental duplications. Expression patterns suggested that most of the CsATG were significantly up- or down-regulated in response to drought; cold; heat; salt; mannitol; and excess manganese, copper, and cadmium stresses. In addition, two ATG18 members, CsATG18a and CsATG18b, were cloned from sweet orange and ectopically expressed in Arabidopsis. The CsATG18a and CsATG18b transgenic plants showed enhanced tolerance to osmotic stress, salt, as well as drought (CsATG18a) or cold (CsATG18b), compared to wild-type plants. These results highlight the essential roles of CsATG genes in abiotic stresses.

From One to Two: In Situ Construction of an Ultrathin 2D-2D Closely Bonded Heterojunction from a Single-Phase Monolayer Nanosheet.

Despite the many attempts to build ultrathin 2D-2D heterojunctions via wet chemical methods, the resulting composite materials reported to date suffer from poor interfacial bonding and/or complexity of the synthetic protocols. Encouraged by the structural compatibility of Bi2WO6 and Bi2O2S, both of which are 2D semiconductors sharing a rather similar structural unit of a [Bi2O2]2+ slice in their crystal structures, we have successfully fabricated an ultrathin nanosheet with a tightly bonded 2D-2D heterojunction between the two components by facilely joining the [Bi2O2]2+ and [S]2- slices using a simple two-step hydrothermal method. Such a Bi2WO6-Bi2O2S 2D-2D heterojunction has a five-alternating-layer (Bi2O2S-Bi2WO6-Bi2O2S-Bi2WO6-Bi2O2S) sandwich structure and a thickness down to ca. 5 nm and was obtained by simply growing the Bi2O2S layer in situ on the surface of monolayer Bi2WO6 nanosheets. The judicious combination of Bi2WO6 and Bi2O2S through a 2D-2D heterojunction not only extended light absorption in the visible range but also significantly enhanced photo(electro)chemical water splitting efficiencies in comparison to the bare Bi2WO6 nanosheets alone due to the close-bonding-promoted interfacial charge separation. Our findings provide a viable methodology to build a host of nanomaterials with closely bonded 2D nanosheets, which can be used as photocatalysts and electrocatalysts, among others.

Whole-transcriptome RNA sequencing reveals the global molecular responses and ceRNA regulatory network of mRNAs, lncRNAs, miRNAs and circRNAs in response to copper toxicity in Ziyang Xiangcheng (Citrus junos Sieb. Ex Tanaka).

BACKGROUND: Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus. RESULTS: Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and 'Ziyang Xiangcheng' (Citrus junos) was found to be the most tolerant genotype. Then the roots and leaves sampled from 'Ziyang Xiangcheng' with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of 'oxidation-reduction', 'phosphorylation', 'membrane', and 'ion binding'. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity. CONCLUSIONS: A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in 'Ziyang Xiangcheng' were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.

Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism.

DEAD-box proteins are a class of nonprocessive RNA helicases that dynamically modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However, the precise roles of individual members are not well understood. Work from our laboratory revealed that the DEAD-box protein Dbp2 in Saccharomyces cerevisiae is an active RNA helicase in vitro that functions in transcription by promoting mRNP assembly, repressing cryptic transcription initiation, and regulating long noncoding RNA activity. Interestingly, Dbp2 is also linked to glucose sensing and hexose transporter gene expression. DDX5 is the mammalian ortholog of Dbp2 that has been implicated in cancer and metabolic syndrome, suggesting that the role of Dbp2 and DDX5 in glucose metabolic regulation is conserved. Herein, we present a refined biochemical and biological comparison of yeast Dbp2 and human DDX5 enzymes. We find that human DDX5 possesses a 10-fold higher unwinding activity than Dbp2, which is partially due to the presence of a mammalian/avian specific C-terminal extension. Interestingly, ectopic expression of DDX5 rescues the cold sensitivity, cryptic initiation defects, and impaired glucose import in dbp2Δ cells, suggesting functional conservation. Consistently, we show that DDX5 promotes glucose uptake and glycolysis in mouse AML12 hepatocyte cells, suggesting that mammalian DDX5 and S. cerevisiae Dbp2 share conserved roles in cellular metabolism.

Enterovirus 71 suppresses interferon responses by blocking Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling through inducing karyopherin-α1 degradation.

Enterovirus 71 (EV71) has emerged as one of the most important enteroviruses since the eradication of poliovirus, and it causes severe neurological symptoms for which no effective antiviral drugs are available. Type I interferons (IFN) α/ß have been used clinically as antiviral therapy as the first line of defense against virus infections successfully for decades. However, treatment with type I interferons has not been effective in patients with EV71 infection. In this study, we found that in cells pretreated with IFN-ß, EV71 infection could still lead to a cytopathic effect, and the viral replication was not affected. The mechanism by which EV71 antagonizes interferon signaling, however, has been controversial. Our study indicated that EV71 infection did not inhibit phosphorylation of STAT1/2 induced by IFN-ß stimulation, but p-STAT1/2 transport into the nucleus was significantly blocked. We showed that EV71 infection reduced the formation of STAT/karyopherin-α1 (KPNA1) complex upon interferon stimulation and that the virus down-regulated the expression of KPNA1, a nuclear localization signal receptor for p-STAT1. Using specific caspase inhibitors and siRNA for caspase-3, we demonstrated that EV71 infection induced degradation of cellular KPNA1 in a caspase-3-dependent manner, which led to decreased induction of interferon-inducible genes and IFN response. Viral 2A and 3C proteases did not degrade KPNA1, inhibit the activity of ISRE or suppress the transcription of interferon-inducible genes induced by IFN-ß. Our study demonstrates a novel mechanism by which antiviral signaling is suppressed through degradation of KPNA1 by activated caspase-3 induced in an enteroviral infection.

Quasi-phase-matched second harmonic generation of long-range surface plasmon polaritons.

In this paper, we experimentally demonstrate the second harmonic generation of long-range surface plasmon polaritons via quasi-phase matching in lithium niobate. After depositing a 9/13 nm thick Au film on periodically poled lithium niobate, TiO2 of about 2.3 µm in thickness is evaporated on the sample as a refractive-index-matching material. This dielectric (periodically poled lithium niobate)-metal(Au)-dielectric(TiO2) sandwich structure can support the transmission of long-range surface plasmon polaritons through it. By designing a moderate ferroelectric domain period of periodically poled lithium niobate, the phase mismatch between the fundamental wave and second harmonic wave of the long-range surface plasmon polaritons can be compensated and a second harmonic wave can be generated effectively. This can be used to provide integrated plasmonic devices with attractive applications in quantum and classic information processing.

Phosphorus Particles Embedded in Reduced Graphene Oxide Matrix to Enhance Capacity and Rate Capability for Capacitive Potassium-Ion Storage.

Early studies indicate that graphite is feasible as the negative electrode of a potassium-ion battery, but its electrochemical performance still cannot meet the demands of applications. More efforts should be focused on increasing the specific capacity and improving the rate capability in the meantime. Thus, stainless-steel autoclave technology has been utilized to prepare phosphorus nanoparticles encapsulated in reduced graphene oxide matrix as the electrode materials for a potassium-ion battery. As a result, the composite matrix affords high reversible capacities of 354 and 253 mA h g-1 at 100 and 500 mA g-1 , respectively. The superior electrochemical performance is mainly because the composite matrix possesses better electronic conductivity and a robust structure, which can promote the electron-transfer performance of the electrode. Furthermore, phosphorus particles can contribute to the high capacity through an alloying mechanism. In addition, the silklike, ultrathin, film composite with a high surface area is conducive to capacitive potassium-ion storage, which plays a more important role in rate performance and a high current density capability.

Critical Role of HAX-1 in Promoting Avian Influenza Virus Replication in Lung Epithelial Cells.

The PB1-F2 protein of influenza A virus has been considered a virulence factor, but its function in inducing apoptosis may be of disadvantage to viral replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown. We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that the mutant virus replicated less efficiently in human lung epithelial cells. The PB1-F2-deficient virus produced less apoptotic cells, indicating that PB1-F2 of the H9N2 virus promotes apoptosis, occurring at the early stage of infection, in the lung epithelial cells. To understand how host cells regulate PB1-F2-induced apoptosis, we explored to identify cellular proteins interacting with PB1-F2 and found that HCLS1-associated protein X-1 (HAX-1), located mainly in the mitochondria as an apoptotic inhibitor, interacted with PB1-F2. Increased procaspase-9 activations, induced by PB1-F2, could be suppressed by HAX-1. In HAX-1 knockdown A549 cells, the replication of AIV H9N2 was suppressed in parallel to the activation of caspase-3 activation, which increased at the early stage of infection. We hypothesize that HAX-1 promotes AIV replication by interacting with PB1-F2, resulting in the suppression of apoptosis, prolonged cell survival, and enhancement of viral replication. Our data suggest that HAX-1 may be a promoting factor for AIV H9N2 replication through desensitizing PB1-F2 from its apoptotic induction in human lung epithelial cells.