Heterologous expression of pediocin/papA in Bacillus subtilis.

Listeria monocytogenes is a food-borne pathogen. Pediocin is a group IIα bacteriocin with anti-listeria activity that is naturally produced by Pediococcus acidilactic and Lactobacillus plantarum. The pedA/papA gene encodes pediocin/plantaricin. In native hosts, the expression and secretion of active PedA/PapA protein rely on the accessory protein PedC/PapC and ABC transporter PedD/PapD on the same operon. The excretion machines were also necessary for pediocin protein expression in heterologous hosts of E. coli, Lactobacillus lactis, and Corynebacterium glutamicum. In this study, two vectors carrying the codon sequence of the mature PapA peptide were constructed, one with and one without a His tag. Both fragments were inserted into the plasmid pHT43 and transformed into Bacillus subtilis WB800N. The strains were induced with IPTG to secrete the fused proteins PA1 and PA2. Supernatants from both recombinant strains can inhibit Listeria monocytogenes ATCC54003 directly. The fused protein possesses inhibition activity as a whole dispense with removal of the leading peptide. This is the first report of active pediocin/PapA expression without the assistance of PedCD/PapCD in heterogeneous hosts. In addition, the PA1 protein can be purified by nickel-nitrilotriacetic acid (Ni-NTA) metal affinity chromatography.

Synthesis of Single-Layer Two-Dimensional Metal-Organic Frameworks M3 (HAT)2 (M=Ni, Fe, Co, HAT=1,4,5,8,9,12-hexaazatriphenylene) Using an On-Surface Reaction.

1,4,5,8,9,12-Hexaazatriphenylene (HAT) is one of the smallest polyheterocyclic aromatic building blocks for forming conjugated metal-organic frameworks (cMOFs). However, the strong inter-molecular steric hindrance impedes the growth of HAT-based cMOFs. Here we employ on-surface synthesis to grow single-layer two-dimensional cMOFs of M3 (HAT)2 (M=Ni, Fe, Co). Using scanning tunnelling microscopy and density-functional theory (DFT) analysis, we resolve that the frameworks comprise a hexagonal lattice of HAT molecules and a Kagome lattice of metal atoms. The DFT analysis indicates that Ni, Co and Fe carry a magnetic moment of 1.1, 2.5, and 3.7 µB, respectively. We anticipate that the small π-conjugated core of HAT and strong bidentate chelating coordination give rise to appealing electronic and magnetic properties.

Association of previous treatment with anti-tumour necrosis factor inhibitors with the effectiveness of secukinumab in the treatment of psoriatic arthritis: systematic review and meta-analysis.

OBJECTIVES: We sought to systematically investigate the effectiveness of secukinumab in psoriatic arthritis (PsA) patients who previously received TNFs inhibitor (TNFi) treatment and those who were TNFi naïve. METHODS: Databases (PubMed, EMBase and Cochrane library) and ClinicalTrials.gov were searched from inception to 22 May 2020 for randomized control trails and observational studies of secukinumab, with or without a history of previous anti-TNFi treatment, in PsA. Effectiveness data were extracted and combined using a random-effects meta-analysis. The ACR20 and ACR50 (20% and 50% improvement in American College of Rheumatology response criteria) responses were the endpoints. RESULTS: Six randomized controlled trials that reported the effectiveness of secukinumab by previous anti-TNFi treatment were included. Among patients exposed to a prior anti-TNFi treatment (n = 738), 33.7% (249/738) of patients achieved an ACR20 response. In contrast, in the anti-TNFi-naïve group (n = 1754), 49.8% (873/1754) of patients achieved an ACR20 response. Prior treatment with anti-TNFi was significantly associated with a poorer response to secukinumab compared with the anti-TNFi-naïve group with an effect size of 2.09 (95% CI: 1.69, 2.58). CONCLUSION: Some patients benefit from switching from TNFi to secukinumab, but previous anti-TNFi treatment is associated with poorer effectiveness of secukinumab.

The role and mechanism of ß-arrestin2 in signal transduction.

ß-arrestin2 is a ubiquitously expressed scaffold protein localized on the cytoplasm and plasma membrane. It was originally found to bind to GPCRs, uncoupling G proteins and receptors' binding and inhibiting the signal transduction of the GPCRs. Further investigations have revealed that ß-arrestin2 not only mediates the desensitization of GPCRs but also serves as a multifunctional scaffold to mediate receptor internalization, kinase activation, and regulation of various signaling pathways, such as TLR4/NF-κB, MAPK, Wnt, TGF-ß, and AMPK/mTOR pathways. ß-arrestin2 regulates cell invasion, migration, autophagy, angiogenesis, and anti-inflammatory effects by regulating various signaling pathways, which play a vital role in many physiological and pathological processes. This paper reviews the structure and function of ß-arrestin2, the regulation of ß-arrestin2 based signaling pathways. The role and mechanism of ß-arrestin2 signaling have been delineated in sufficient detail. The prospect of regulating the expression and activity of ß-arrestin2 in multisystem diseases holds substantial therapeutic promise.

Fourty-nine years old woman co-infected with SARS-CoV-2 and Mycoplasma: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the outbreak of respiratory illness known as coronavirus disease 2019 (CoVID-19). Mycoplasma is an uncommon co-infected pathogen with SARS-CoV-2 and has not yet been reported. Computed tomography (CT), used as an accessory examination, may play a more significant role in this co-infection. CASE SUMMARY: A 49-year-old female presented with a cough, expectoration and chest congestion followed by elevated C-reactive protein and erythrocyte sedimentation rate. CT images showed ground-glass opacities in bilateral lower lobes and a patchy and striate shadow in the right upper lobe. Immunoglobulin M antibody of Mycoplasma pneumoniae was positive and real-time fluorescence polymerase chain reaction of sputum was positive for SARS-CoV-2 nucleic acid. The diagnosis of CoVID-19 was made based on laboratory results, chest CT images, clinical manifestations and epidemiologic characteristics. She was treated with combination therapy for 17 d and showed a marked reCoVery. CONCLUSION: Co-infection with SARS-CoV-2 and Mycoplasma in CoVID-19 patients appears to be uncommon. CT is an acceptable method for the primary diagnosis and treatment should be initiated as soon as possible. Combination therapy with antiviral, anti-inflammatory, traditional Chinese herbal medicine and interferon inhalation may be a reference for further progress in treating this co-infection.

Synthesis and characterization of a single-layer conjugated metal-organic structure featuring a non-trivial topological gap.

We employ an on-surface assembly protocol to synthesize a single layer of a two-dimensional conjugated network (Ni3(HITP)2) on a Au(111) surface. The electronic coupling between the π orbital of the diimine ligand and the d orbital of the metal ion renders efficient π-conjugation. Density-functional theory calculations provide evidence of a non-trivial topological gap in the surface-adsorbed single layer. This work demonstrates that single-layer 2D metal-organic frameworks adsorbed on surfaces are a new class of 2D materials that host quantum phases.