Toxic Characteristics and Action Mode of the Mixotrophic Dinoflagellate Akashiwo sanguinea on Co-Occurring Phytoplankton and Zooplankton

The mixotrophic dinoflagellate Akashiwo sanguinea frequently forms harmful algal blooms around the world and has caused massive deaths of shellfish, finfish and birds, yet its toxic mechanism is still unclear. In this study, toxic effects of A. sanguinea on co-culturing phytoplankton and zooplankton were investigated. The results showed that sonicated cultures of A. sanguinea JX13 and JX14, isolated from the Pearl River Estuary, had a significant lethal effect on the rotifer Brachionus plicatilis, with the highest mortality rate of 80%. The highest inhibition rates of A. sanguinea cultures JX13 (90%) and JX14 (80%) on R. salina were much higher than that of AS2 (20%). Toxicity varied with the growth stage, during which A. sanguinea cells in the exponential stage showed the highest toxicity (40%), while A. sanguinea filtrate had the highest toxicity (10%) in the decline stage. The action mode of A. sanguinea toxicity on plankton was explored through an osmotic membrane culture device. It was found that A. sanguinea JX13 displayed an inhibitory effect on coexisting phytoplankton, whether they had contact or not, but the inhibition rate increased by 25% with contact. A lethal effect of A. sanguinea JX13 on rotifer Brachionus plicatilis was observed only in contact treatment. This study suggests that direct contact is the key action mode to trigger the release of toxins and induce toxic effects of A. sanguinea on co-occurring plankton.

LncRNA MIR155HG functions as a ceRNA of miR-223-3p to promote cell pyroptosis in human degenerative NP cells

Nucleus pulposus (NP) cell pyroptosis plays a critical role in the pathogenesis of intervertebral disk degeneration (IDD). MIR155 host gene (MIR155HG) is a long non-coding RNA with pro-inflammatory activity. However, very little is known about its role in NP cell pyroptosis. This study aimed to observe the impact of MIR155HG on cell pyroptosis and to explore the underlying mechanism in human degenerative NP cells. Our results demonstrated that MIR155HG expression was significantly increased in human degenerative NP tissue samples and showed a positive correlation with Pfirrmann score. Overexpression of MIR155HG through a lentiviral vector decreased miR-223-3p levels, up-regulated NLRP3 expression and induced cell pyroptosis in human degenerative NP cells. A ceRNA action mode was identified among MIR155HG, miR-223-3p and NLRP3. The stimulatory effect of MIR155HG on human degenerative NP cell pyroptosis was significantly reversed by pretreatment with miR-223-3p mimic or NLRP3 siRNA. In summary, these data suggest that MIR155HG sponges miR-223-3p to promote NLRP3 expression, leading to induction of cell pyroptosis in human degenerative NP cells. Targeting MIR155HG could be a novel and promising strategy to slow down the progression of IDD.

Retapamulin: Current Status and Future Perspectives

: Retapamulin is one of the antibiotics recently developed semi-synthetically to inhibit protein synthesis in a specific manner different from other antibiotics. This pleuromutilin derivative shows magnificent anti-bacterial activity in Gram-positive pathogens, especially Staphylococcus aureus and Streptococcus pyogenes, and now it is available in ointment formulations (1%) for clinical use with negligible side effects. Despite the low potential for resistance development, antimicrobial susceptibility rates are significantly high. This is especially important when the prevalence of mupirocin-resistant strains is increasing, and the need for new alternatives is urgent. Unfortunately, due to its oxidation by cytochrome p450, this drug cannot be used systemically. However, another pleuromutilin derivative with systemic use, lefamulin, was approved in August 2019 by the US Food and Drug Administration. In addition to pharmacokinetic features, financial issues are also barriers to consider in the progress of new antimicrobials. In this review, we attempt to take a brief look at the derivatives usable in humans and explore their structures, action mode, metabolism, possible ways of resistance, resistance rates, and their clinical use to explain and highlight the valuable points of these antibiotics.

Past and Current Progress in the Development of Antiviral/Antimicrobial Polymer Coating towards COVID-19 Prevention: A Review

The astonishing outbreak of SARS-CoV-2 coronavirus, known as COVID-19, has attracted numerous research interests, particularly regarding fabricating antimicrobial surface coatings. This initiative is aimed at overcoming and minimizing viral and bacterial transmission to the human. When contaminated droplets from an infected individual land onto common surfaces, SARS-CoV-2 coronavirus is able to survive on various surfaces for up to 9 days. Thus, the possibility of virus transmission increases after touching or being in contact with contaminated surfaces. Herein, we aim to provide overviews of various types of antiviral and antimicrobial coating agents, such as antimicrobial polymer-based coating, metal-based coating, functional nanomaterial, and nanocomposite-based coating. The action mode for each type of antimicrobial agent against pathogens is elaborated. In addition, surface properties of the designed antiviral and antimicrobial polymer coating with their influencing factors are discussed in this review. This paper also exhibits several techniques on surface modification to improve surface properties. Various developed research on the development of antiviral/antimicrobial polymer coating to curb the COVID-19 pandemic are also presented in this review.

Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription

The members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family play vital roles in multiple biological processes, including DNA damage response, metabolism, cell growth, mRNA decay, and transcription. TRRAP, as the only member lacking the enzymatic activity in this family, is an adaptor protein for several histone acetyltransferase (HAT) complexes and a scaffold protein for multiple transcription factors. TRRAP has been demonstrated to regulate various cellular functions in cell cycle progression, cell stemness maintenance and differentiation, as well as neural homeostasis. TRRAP is known to be an important orchestrator of many molecular machineries in gene transcription by modulating the activity of some key transcription factors, including E2F1, c-Myc, p53, and recently, Sp1. This review summarizes the biological and biochemical studies on the action mode of TRRAP together with the transcription factors, focusing on how TRRAP-HAT mediates the transactivation of Sp1-governing biological processes, including neurodegeneration.

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e–f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl2 or 5f with 3,4-Cl2). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC50 = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160–4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-N,N′,N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.

Efficient Degradation of Alginate And Preparation of Unsaturated Monosaccharides By A Novel Alginate Lyase And Effects of Domain Truncation On Biochemical Characteristics, Degradation Patterns

BackgroundBrown algae are considered promising crops for the production of sustainable biofuels. However, its commercial application has been limited by lack of efficient methods for converting alginate into fermentable sugars. Recently, exo-type alginate lyases have received extensive attention due to their excellent ability of conversion of alginate into 4-deoxy-L-erythro-5-hexoseulose uronate (DEH), a promising material for bioethanol production and biorefinery systems.ResultsHerein, we cloned and characterized a novel alginate lyase AlyPL17 from Pedobacter hainanensis NJ-02. It possessed outstanding catalytic efficiency towards polymannuronic acid (polyM), polyguluronic acid (polyG) and alginate sodium, with kcat of 39.42 + 1.9 s-1, 32.53 + 0.88 s-1, and 38.30 + 2.12 s-1, respectively. In addition, AlyPL17 adopts a unique hybrid action mode to degrade alginate by the synergistic effect of two domains. Furthermore, the combination of AlyPL17 and AlyPL6 exhibited apparently synergistic effect for the preparation of unsaturated monosaccharides. ConclusionOverall, the results show that AlyPL17 is a PL17 exo-type alginate lyase with high activity and a high conversion rate at low/moderate temperatures, which provides a useful enzymatic tool for the conversion of brown algae into biofuels and enhance our understanding of the function of modular domain of alginate lyase.