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.

Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA.

Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.

Enhanced Molecularly Imprinted Fluorescent Test Strip for Rapid and Visual Detection of Norfloxacin via a Smartphone.

Paper-based test strips with on-site visual detection have become a hot spot in the field of target detection. Yet, low specific surface area and uneven deposition limit the further application of test strips. Herein, a novel "turn-on" ratio of molecularly imprinted membranes (Eu@CDs-MIMs) was successfully prepared based on a Eu complex-doped polyvinylidene fluoride membrane for the selective, rapid and on-site visual detection of norfloxacin (NOR). The formation of surface-imprinted polymer-containing carbon dots (CDs) improves the roughness and hydrophilicity of Eu@CDs-MIMs. Fluorescence lifetimes and UV absorption spectra verified that the fluorescence enhancement of CDs is based on the synergistic effect of charge transfer and hydrogen bonding between CDs and NOR. The fluorescent test strip showed a linear fluorescent response within the concentration range of 5-50 nM with a limit of detection of 1.35 nM and a short response time of 1 min. In comparison with filter paper-based test strips, Eu@CDs-MIMs exhibit a brighter and more uniform fluorescent color change from red to blue that is visible to the naked eye. Additionally, the applied ratio fluorescent test strip was combined with a smartphone to translate RGB values into concentrations for the visual and quantitative detection of NOR and verified the detection results using high-performance liquid chromatography. The portable fluorescent test strip provides a reliable approach for the rapid, visual, and on-site detection of NOR and quinolones.

LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity.

Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNA Malat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. Malat1 directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degrading Rbck1 pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency of Malat1 enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reduced MALAT1, augmented IRF3, and increased IFNA mRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation of MALAT1 in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclear Malat1 suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis.

RNA-binding protein hnRNP UL1 binds κB sites to attenuate NF-κB-mediated inflammation.

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a family of RNA-binding proteins, play important roles in various biological processes. However, the roles of hnRNPs members in immunity and inflammation remain to be fully understood. By a functional screening for hnRNPs members in LPS-stimulated macrophage inflammatory response, we identified hnRNP UL1 as a negative regulator of NF-κB-mediated inflammation. hnRNP UL1 constrains NF-κB-triggered transcriptional expression of pro-inflammatory cytokines in response to innate stimuli. Perturbation of hnRNP UL1 enhanced pro-inflammatory cytokine production in macrophages. In vivo deficiency of hnRNP UL1 increased the pro-inflammatory cytokine production once challenged with LPS. Accordingly, the expression of hnRNP UL1 decreased in peripheral blood mononuclear cells of rheumatoid arthritis patients. Mechanistically, hnRNP UL1 competes with NF-κB to bind κB sites to constrain the magnitude and duration of inflammatory response. Meanwhile, the broadly and dynamically binding of hnRNP UL1 on the target genes' promoter during inflammatory response is unraveled. Our study adds new insight into the functions of hnRNPs in NF-κB-mediated inflammation, proposing a potential therapeutic strategy for controlling inflammatory autoimmune diseases.

Construction of vesicle CdSe nano-semiconductors photocatalysts with improved photocatalytic activity: Enhanced photo induced carriers separation efficiency and mechanism insight.

Visible-light-driven photocatalysis as a green technology has attracted a lot of attention due to its potential applications in environmental remediation. Vesicle CdSe nano-semiconductor photocatalyst are successfully prepared by a gas template method and characterized by a variety of methods. The vesicle CdSe nano-semiconductors display enhanced photocatalytic performance for the degradation of tetracycline hydrochloride, the photodegradation rate of 78.824% was achieved by vesicle CdSe, which exhibited an increase of 31.779% compared to granular CdSe. Such an exceptional photocatalytic capability can be attributed to the unique structure of the vesicle CdSe nano-semiconductor with enhanced light absorption ability and excellent carrier transport capability. Meanwhile, the large surface area of the vesicle CdSe nano-semiconductor can increase the contact probability between catalyst and target and provide more surface-active centers. The photocatalytic mechanisms are analyzed by active species quenching. It indicates that h+ and O2- are the main active species which play a major role in catalyzing environmental toxic pollutants. Simultaneously, the vesicle CdSe nano-semiconductor had high efficiency and stability.

Enhanced Recyclability, Stability, and Selectivity of CdS/C@Fe3O4 Nanoreactors for Orientation Photodegradation of Ciprofloxacin.

A unique CdS/C@Fe3O4 nanoreactor was fabricated by the surface-imprinting technique, which effectively enhances the recyclability, stability, and selectivity for orientation recognition and photodegradation of ciprofloxacin in the binary mixed solution under visible-light irradiation. This work not only puts forward a novel design idea that develops the potential application value of CdS, but also provides a new approach for inhibiting its secondary pollution.

Hollow molecularly imprinted fluorescent sensor using europium complex as functional monomer for the detection of trace 2,4,6-trichlorophenol in real water samples.

As an important environmental indicator, 2,4,6-trichlorophenol (2,4,6-TCP) was proved extremely harmful to human body. In this article, hollow molecularly imprinted fluorescent polymers (@MIPs) for the selective detection of 2,4,6-TCP were devised and fabricated by sacrificial skeleton method based on SiO2 nanoparticles. As the most innovation, highly luminescent europium complex Eu(MAA)3phen played the role of both fluorophores and functional monomers of the MIPs. The obtained @MIPs showed monodispersity and the average particle size was around 130 nm. It had a linear fluorescent response within the concentration range 10-100 nmol L-1 with the correlation coefficient calculated as 0.99625, and the limit of detection was identified as 2.41 nmol L-1. The results show that Eu(MAA)3phen as a fluorophore has high luminescent properties, and as a functional monomer, it can improve the selectivity and anti-interference performance of MIPs. Furthermore, the hollow structure made it possible that the imprinted specific recognition sites distributed on both inner and outer surfaces of @MIPs. The experimental results showed that these @MIPs could be employed to the selective detection of chlorophenols under low concentration. And this work will provide a reference for further optimization of fluorescent imprinted sensors.

Novel Molecular Organic Framework Composite Molecularly Imprinted Nanofibrous Membranes with a Bioinspired Viscid Bead Structure for Selective Recognition and Separation of Atrazine.

In this work, novel atrazine (ATZ) molecularly imprinted nanofibrous membranes (A-MNMs) with a molecular organic framework (MOF)-based viscid bead structure were developed based on a natural spider-web-inspired strategy for selective separation of ATZ. Poly(vinylidene fluoride)/poly(vinyl alcohol) (PVDF/PVA) blended nanofibrous membranes as the basal membrane were synthesized by electrospinning technology combined with a chemical cross-linking procedure. The most critical design is that MOF nanocrystals as the matrix of the viscid bead structure were assembled on the PVDF/PVA blended nanofibrous membrane surface and the specific recognition sites were efficiently constructed on the surface and pores of the MOF-based viscid bead structure by a surface imprinting strategy. Significantly, the as-synthesized MOF-based viscid bead structure has an enhanced specific surface area, which helps to form abundant specific recognition sites in A-MNMs. Therefore, the A-MNMs with a spider-web-like structure presented an enhanced rebinding capacity (37.62 mg g-1) and permselectivity (permselectivity factors ß were 4.21 and 4.31) toward ATZ. Moreover, the A-MNMs display strong practicability in separation of ATZ from simulated environmental water samples. The presented work has shown tremendous potential for preparing natural spider-web-like molecularly imprinted membranes (MIMs) for selective separation of environment pollutants.

E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells.

Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.

Bio-inspired fabrication of Ester-functionalized imprinted composite membrane for rapid and high-efficient recovery of lithium ion from seawater.

Lithium ion (Li+) is one of the important sustainable resource and it's urgently demanded to develop high-selectivity and high-efficient method to extract of Li+ from seawater. Hence, we propose the ester-functionalized ion-imprinted membrane (IIMs) with high selectivity and stability for the rebinding and separation of Li+ in aqueous medium via ion imprinted technology and membrane separation technology. In this work, the hydrophilic polydimethylsiloxane membranes (PDMS) are synthesized by self-polymerization of dopamine (DA) in aqueous solution, resulting in the fabrication of dense poly-dopamine (PDA) layer on the surface of PDMS (PDMS-PDA). In view of weak bonding forces (such as hydrogen bond, ionic bond and Van der Waals' force) between traditional imprinted polymer and ligand, the ester groups are formed between modified PDMS-PDA and ligand by surface grafting. The obtained Li+ imprinted membranes (Li-IIMs) have a suitable cavity and high adsorption capacity toward Li+ which reveal a high rebinding capacity (50.872 mg g-1) toward Li+ based on ample rebinding sites and strong affinity force. The superior relative selectivity coefficients (αNa/Li, αK/Li and αRb/Li are 1.71, 4.56 and 3.80, respectively) can be also achieved. The selectivity factors of Li-IIMs for Na+, K+ and Rb+ are estimated to be 2.52, 2.8 and 3.03 times larger than Li+ non-imprinted membranes (Li-NIMs), which imply the superior selectivity of Li-IIMs toward Li+. The regeneration ability of Li-IIMs is observed by systematic batch experiments. In summary, it can be concluded that the rebinding capacities of Li-IIMs is slightly decrease after eluting process, owing to the Li-IIMs with outstanding stability performance. Presentation of the method pave a fine prospect for coming true the long-term use of imprinted membrane.

Anti-inflammatory effect of resveratrol on adjuvant arthritis rats with abnormal immunological function via the reduction of cyclooxygenase-2 and prostaglandin E2.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with unknown etiology. The present study investigated the anti-inflammatory effect of resveratrol on rats with adjuvant arthritis (AA) with abnormal immunological function via the reduction of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). AA model rats were established by injection of complete Freund's adjuvant and alterations in the rats secondary paw swelling and the polyarthritic scores were observed. Pathological examination of joint tissues was observed by hematoxylin and eosin staining. The proliferation of spleen cells was examined using a 3-(4,5-dimethylthiazol-2­yl)-2,5-diphenyltetrazolium bromide assay in vitro. The protein expression of COX-2 in the synovial tissues was detected by western blotting. The level of PGE2 in the serum was assayed using an ELISA kit. The results demonstrated that resveratrol (10 or 50 mg/kg) was able to significantly reduce paw swelling and decrease the arthritis scores. Compared with the AA model rats, a significant reduction in the proliferation of concanavalin A-stimulated spleen cells was observed, articular cartilage degeneration with synovial hyperplasia and inflammatory cell infiltration was suppressed and the production of COX-2 and PGE2 in AA rats was reduced by treatment with resveratrol. These results suggest that resveratrol has significant anti-inflammatory effects on AA rats, which may be associated with the reduction of COX-2 and PGE2 inflammatory mediators.

[Genomic characteristics of coxsackievirus B5 A210/KM/09 strain isolated in Yunnan, China].

OBJECTIVE: To characterize the complete genome sequence of coxsackievirus B5 (CVB5)A210/KM/09 strain which was isolated from Yunnan, China, 2009. METHODS: Eight overlapping clones covering the whole viral genome (excluding the poly-A tail)were obtained by RT-PCR and sequenced, with their nucleotide and amino acid sequences compared with other known CVB5 strains. RESULTS: The genome of the CVB5 A210/KM/09 strain had 7 372 nucleotides in length, and containing a 742-nt non-translated region (NTR) at the 5' end and a 98-nt NTR at the 3' end. The entire open reading frame contained 6 555 nt, encoding a 2 185-aa polyprotein. In the coding region, there appeared no nucleotide deletion or insertion, but some changes of amino acid seemed unique. Based on the complete genome sequence alignments, CVB5 isolate A210/KM/09 strain showed the highest nucleotide (92.5%) and amino acid (97.3%) identities to the CVB5/CC10/10. It also shared nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) homology with other CVB5 strains: 17Y, 19CSF, 20CSF, 1954/85/US, 2000/CSF/KOR, 03001N, CoxB5/Henan/2010, VB5/SD/09 and Faulkner. Blast between genome fragments, A210/KM/09 showed similarity on nucleotide (80.1%-92.5%) and amino acid (95.0%-97.3%) identities with other CVB5 strains. The phylogenetic tree, constructed on the complete VP1 regions, indicated that CVB5 could be divided into genotype A, B, C and D. while Genotype C and D could be further divided into C1-C4 and D1-D4 subgenotypes. CONCLUSION: A210/KM/09 and other CVB5 predominant strains isolated in China belonged to CVB5 subgenotype C4.

[Complete nucleotide sequence of a human coxsackievirus B3 strain A103/KM/09 isolated in Yunnan province, 2009].

OBJECTIVE: To analyze the genetic characterization of the complete genome from a human coxsackievirus B3 strain A103/KM/09 isolated in Yunnan province, 2009. METHODS: By using RT-PCR, all the eight fragments which containing about 1000 nucleotides and covering full viral genome, were sequenced. By using Mega 5.05,Geneious, RDP 3 and SimPlot 3.5.1 software, sequences were aligned with other enterovirus reference sequences. Phylogenetic and recombination analysis were also carried out. RESULTS: The A103/KM/09 isolate genome showed 7389 nucleotides in length , encoding for 2185 amino acids. In the complete genome, the homology of nucleotide and amino acid among the seven coxsackievirus B3 isolates were 81.0%-88.0% and 95.7%-98.0%, respectively. There appeared 81.0% and 95.7% homology when compared with that of Nancy prototype strain. Results from the Phylogenetic analysis showed that the coxsackievirus B3 formed five distinct clades, I-V. Nucleotide divergence rates between clades were 16.2%-24.3% . The A103/KM/09 strain belonged to clade V. Clade V was further divided into four sub-clades,A-D. The nucleotide divergence between sub-clades was 4.3%-11.4%. Putative recombinant event for A103/ KM/09 was detected. CONCLUSION: All coxsackievirus B3 isolates could be divided into five clades, with A103/KM/09 strain belonged to Clade V-D. Evolution of coxsackievirus B3 had occurred in China.

[Complete nucleotide sequence of a human echovirus 6 strain KM57-09 isolated in Yunnan, China, in 2009].

OBJECTIVE: To analyze the genetic characterization of the complete genome from a human echovirus 6 (Echo6) strain KM57-09 isolated in Yunnan, China, in 2009. METHODS: Using the RT-PCR, eight fragments containing about 1000 nucleotides which covered the whole viral genome were sequenced. The sequences were aligned with other reference enterovirus sequences downloaded from the GenBank, using Mega 5.05, RDP 3 and SimPlot 3.5.1 softwares. RESULTS: Similar to the other human enterovirus, KM57-09 isolate genome appeared to have 7419 nucleotides in length, encoding for 2191 amino acids. In the complete genome, the rates of homology on nucleotide and amino acid among the seven Echo6 isolates were 79.3% - 80.2% and 93.3% - 94.4%, respectively as well as 79.3% and 93.6% of the rates of homology when compared with that of D' Amor prototype strain. In different segment of genome. The 2C-3A genome region was most similar to the HN-2-E25 strain, the 5' UTR, VP4, 3D and 3' UTR genome region were most similar to the CoxB5-Henan-2010. In the VP1 gene, the rates of homology on nucleotide and amino acid among the China isolates were 80.0% - 96.0% and 95.8% - 99.0%, respectively, and showed 77.6% - 96.0% and 95.2% - 99.0% of the rates on homology when compared to the other Echo6 reference strains isolated from other countries or areas, respectively. RESULTS: from phylogenetic analysis showed that the Echo6 formed five distinct groups, A-E. The KM57-09 strain belonged to clade E. The nucleotide divergence between clades was 15.6% - 23.3%. The putative recombinant event for KM57-09 was detected with RDP 3, SimPlot 3.5.1 and 3D sequence phylogenetic analysis. CONCLUSION: All the Echo6 isolates could be divided into five clades, the KM57-09 strain belonged to Clade E. The Echo6 strains isolated in China were contributed to several different chains of transmission.