Host Lipids in Positive-Strand RNA Virus Genome Replication

Membrane association is a hallmark of the genome replication of positive-strand RNA viruses [(+)RNA viruses]. All well-studied (+)RNA viruses remodel host membranes and lipid metabolism through orchestrated virus-host interactions to create a suitable microenvironment to survive and thrive in host cells. Recent research has shown that host lipids, as major components of cellular membranes, play key roles in the replication of multiple (+)RNA viruses. This review focuses on how (+)RNA viruses manipulate host lipid synthesis and metabolism to facilitate their genomic RNA replication, and how interference with the cellular lipid metabolism affects viral replication

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum

The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor polyprenol, are unusual in eukaryotic cells. Our metabolomics studies revealed that cis-polyisoprenoids are more diverse in the malaria parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite’s development. Moreover, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite

An Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid Vesicles

Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices. It has been conventionally recognized that these helices serve as an anchor for viral replication protein to be associated with membranes. We report here that a peptide representing the amphipathic α-helix at the N-terminus of the poliovirus 2C protein not only binds to liposomes, but also remodels spherical liposomes into tubules. The membrane remodeling ability of this amphipathic alpha-helix is similar to that recognized in other amphipathic alpha-helices from cellular proteins involved in membrane remodeling, such as BAR domain proteins. Mutations affecting the hydrophobic face of the amphipathic alpha-helix severely compromised membrane remodeling of vesicles with physiologically relevant phospholipid composition. These mutations also affected the ability of poliovirus to form plaques indicative of reduced viral replication, further underscoring the importance of membrane remodeling by the amphipathic alpha-helix in possible relation to the formation of viral replication complexes

Programmed 6-Step Approach of Improved Liposuction-Curettage for Axillary Bromhidrosis

ABSTRACT: Background: Liposuction-curettage is a long-standing and effective treatment for axillary bromhidrosis. However, residual malodor and skin necrosis typically occur following this treatment. Therefore, we improved this method to ensure fewer complications and better outcomes. Here, we have presented our programmed 6-step approach of improved liposuction-curettage. Methods: The programmed 6-step approach of improved liposuction-curettage was used to remove the axillary apocrine glands. We used pointed and obtuse cannulas designed for liposuction-curettage. Results: Patients treated using the programmed 6-step approach of improved liposuction-curettage did not experience any serious complications or residual malodor. Conclusion: The programmed 6-step approach of improved liposuction-curettage was more effective than traditional surgery with respect to the treatment of axillary bromhidrosis

Access to green primary explosives via constructing coordination polymers based on bis-tetrazole oxide and non-lead metals

An environmentally friendly method to prepare new-generation green primary explosives with excellent performances has been developed on the basis of a coordination chemistry strategy. In the present work, constructing energetic coordination polymers (ECPs) based on tetrazole oxide 1H, 1' H-[ 5,5'-bitetrazole]1,1'- diol (H2BTO) with non-heavy metal cations Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) led to five novel green primary explosives without metal ion and organic pollution. Systematic research is conducted to prove these green ECPs as a novel class of lead-free primary explosives. For example, a thermal stability experiment shows that their thermal decomposition temperatures are all beyond 200 degrees C, while the thermalresistance experiment demonstrates that compounds 1 and 5 can maintain long-term stability under 100 degrees C. And the results based on sensitivity tests and detonation parameter simulation reveal that all these compounds possess excellent detonation and safety properties, far outperforming classical primary explosives such as lead azide. Moreover, a modified Koenen test has been conducted to characterize the explosion capacity of these ECPs and by this method compounds 1, 2, 3, and 5 were demonstrated with fast deflagration-to-detonation transition ability

Exogenous melatonin confers cold tolerance in rapeseed (Brassica napus L.) seedlings by improving antioxidants and genes expression

Rapeseed (Brassica napus L.) is an important oilseed crop globally. However, its growth and production are significantly influenced by cold stress. To reveal the protective role of exogenous melatonin (MEL) in cold tolerance, rapeseed seedlings were pretreated with different concentrations of MEL before cold stress. The results indicated that the survival rate was increased significantly by the MEL pretreatment under cold stress. Seedlings pretreated with 0.01 g L−1 MEL were all survived and were used to analyze the physiological characteristics and the expression level of various genes related to cold tolerance. Under cold stress, exogenous MEL significantly increased the contents of proline, soluble sugar, and soluble protein; while the malondialdehyde content was decreased by exogenous MEL under cold stress. On the other hand, the activities of antioxidant defense enzymes such as catalase, peroxidase, and superoxide dismutase were also significantly enhanced. The results also showed that MEL treatment significantly upregulated the expression of Cu-SOD, COR6.6 (cold-regulated), COR15, and CBFs (C-repeat binding factor) genes under cold stress. It was suggested exogenous MEL improved the content of osmotic regulatory substances to maintain the balance of cellular osmotic potential under cold stress and improved the scavenging capacity of reactive oxygen species by strengthening the activity of antioxidant enzymes and the cold-related genes expression

CRISPR/Cas9-mediated resistance to cauliflower mosaic virus.

Viral diseases are a leading cause of worldwide yield losses in crop production. Breeding of resistance genes (R gene) into elite crop cultivars has been the standard and most cost-effective practice. However, R gene-mediated resistance is limited by the available R genes within genetic resources and in many cases, by strain specificity. Therefore, it is important to generate new and broad-spectrum antiviral strategies. The CRISPR-Cas9 (clustered regularly interspaced palindromic repeat, CRISPR-associated) editing system has been employed to confer resistance to human viruses and several plant single-stranded DNA geminiviruses, pointing out the possible application of the CRISPR-Cas9 system for virus control. Here, we demonstrate that strong viral resistance to cauliflower mosaic virus (CaMV), a pararetrovirus with a double-stranded DNA genome, can be achieved through Cas9-mediated multiplex targeting of the viral coat protein sequence. We further show that small interfering RNAs (siRNA) are produced and mostly map to the 3 end of single-guide RNAs (sgRNA), although very low levels of siRNAs map to the spacer region as well. However, these siRNAs are not responsible for the inhibited CaMV infection because there is no resistance if Cas9 is not present. We have also observed edited viruses in systematically infected leaves in some transgenic plants, with short deletions or insertions consistent with Cas9-induced DNA breaks at the sgRNA target sites in coat protein coding sequence. These edited coat proteins, in most cases, led to earlier translation stop and thus, nonfunctional coat proteins. We also recovered wild-type CP sequence in these infected transgenic plants, suggesting these edited viral genomes were packaged by wild-type coat proteins. Our data demonstrate that the CRISPR-Cas9 system can be used for virus control against plant pararetroviruses with further modifications

Bisdemethoxycurcumin exerts a cell-protective effect via JAK2/STAT3 signaling in a rotenone-induced Parkinson’s disease model in vitro

Introduction. Oxidative stress and cell apoptosis have both been suggested to be closely associated with the pathogenesis of Parkinson’s disease (PD). Previously, bisdemethoxycurcumin (BDMC) has been shown to exhibit several desirable characteristics as a candidate neuroprotective agent, including antioxidant and anti-inflammatory activities in the nervous system. However, whether BDMC can exert cell-protective roles in an in vitro model of PD remains unknown. Material and methods. SH-SY5Y cells were pretreated with BDMC, with or without AG490 and SI-201, for 30 min, followed by a co-incubation with rotenone for 24 h. Subsequently, a cell viability assay and western blotting was performed, and SOD and GSH activities were analyzed. Results. The results revealed that the pretreatment with BDMC enhanced the cell survival, antioxidative stress capacity and the phosphorylation levels of JAK/STAT3 in SH-SY5Y cells treated with rotenone. However, following the incubation with AG490 and SI-201, inhibitors of the JAK/STAT3 signaling pathway, BDMC was unable to exert cell-protective roles in SH-SY5Y cells treated with rotenone. Conclusions. In conclusion, the results suggested that BDMC may exert a cell-protective role in SH-SY5Y cells in vitro via JAK2/STAT3 signaling, thus suggesting the possible application of BDMC for the treatment of neurodegenerative diseases related to JAK2/STAT3 signaling