Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine sulfated glycans

The Coronavirus disease pandemic has steered the global therapeutic research efforts toward the discovery of potential anti-severe acute respiratory syndrome coronavirus (SARS-CoV-2) molecules. The role of the viral spike glycoprotein (S-protein) has been clearly established in SARS-CoV-2 infection through its capacity to bind to the host cell surface heparan sulfate proteoglycan (HSPG) and angiotensin-converting enzyme-2. The antiviral strategies targeting these 2 virus receptors are currently under intense investigation. However, the rapid evolution of the SARS-CoV-2 genome has resulted in numerous mutations in the S-protein posing a significant challenge for the design of S-protein-targeted inhibitors. As an example, the 2 key mutations in the S-protein receptor-binding domain (RBD), L452R, and T478K in the SARS-CoV-2 Delta variant (B.1.617.2) confer tighter binding to the host epithelial cells. Marine sulfated glycans (MSGs) demonstrate excellent inhibitory activity against SARS-CoV-2 via competitive disruption of the S-protein RBD-HSPG interactions and thus have the potential to be developed into effective prophylactic and therapeutic molecules. In this study, 7 different MSGs were evaluated for their anti-SARS-CoV-2 activity in a virus entry assay utilizing a SARS-CoV-2 pseudovirus coated with S-protein of the wild-type (Wuhan-Hu-1) or the Delta (B.1.617.2) strain. Although all tested MSGs showed strong inhibitory activity against both strains, no correlations between MSG structural features and virus inhibition could be drawn. Nevertheless, the current study provides evidence for the maintenance of inhibitory activity of MSGs against evolving SARS-CoV-2 strains

A Case Report of Painless Moving Toes Syndrome

This is the first report of a case of painless moving toes syndrome with radiculopathy. The patient presented with bilateral painless moving toes and unilateral subclinical sacral (S1) radiculopathy. Bilateral movements with the unilateral lesion, and fluctuation with postural changes and distant muscle contraction suggest that the underlying pathomechanism was a central reorganization in the spinal level

Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products had weak anticoagulant activities as seen by aPTT and inhibitory assays using purified cofactors. In contrast, lower MW BoSG-derivatives retained anti-SARS-CoV-2 activity using SARS-CoV-2 spike (S)-protein pseudotyped lentivirus vector in HEK-293T-hACE2 cells monitored by GFP. Surface plasmon resonance confirmed that longer chains are necessary for BoSG to interact with coagulation cofactors but is not required for interactions with certain S-protein variants. We observed distinct affinities of BoSG derivatives for the S-proteins of different SARS-CoV-2 strains, including WT, N501Y (Alpha), K417T/E484K/N501Y (Gamma), and L542R (Delta) mutants, and stronger affinity for the N501Y-containing variants. Docking of the four possible monosulfated BoSG disaccharides in interactions with the N501Y mutant S-protein predicted potential binding poses of the BoSG constructs and favorable binding in close proximity to the 501Y residue. Our results demonstrate that depolymerization and fractionation of BoSG are an effective strategy to segregate its anticoagulant property from its anti-SARS-CoV-2 action

Study on fatigue experiment for transverse butt weldsunder 2G and 3G weld positions

ABSTRACTAlthough the transverse butt weld method with ceramic backing strip has been widely used in various industrial fields for its fabricational convenience, it is rarely used in offshore industries since the fatigue strength of the weld joint has not been proved sufficiently. This study conducted fatigue tests for series of butt weld specimens with horizontal (2G) and vertical (3G) welding positions in order to verify the fatigue strength compared to S-N curve by DNV (Det Norske Veritas), IIW (International Institute of Welding) and Eurocode 3. The difference of the 2G specimens and the 3G specimens are investigated in terms of angular distortion and the effect on the fatigue strength are analyzed

Application of PEEP using the i-gel during volume-controlled ventilation in anesthetized, paralyzed patients

PURPOSE: This prospective, randomized trial was designed to assess whether the i-gel supraglottic airway device is suitable for volume-controlled ventilation while applying positive end-expiratory pressure (PEEP) of 5 cmH(2)O under general anesthesia. It was believed that this device might improve arterial oxygenation. METHODS: Forty adult patients (aged 20–60 years) scheduled for elective orthopedic surgery were enrolled in this study. Twenty patients were ventilated without external PEEP [zero positive end-expiratory pressure (ZEEP) group], and the other 20 were ventilated with PEEP 5 cmH(2)O (PEEP group) after placing an i-gel device. Volume-controlled ventilation at a tidal volume (TV) of 8 ml/kg of ideal body weight, leak volume, and arterial blood gas analysis were investigated. RESULTS: The incidences of a significant leak were similar in the ZEEP and PEEP groups (3/20 and 1/20, respectively; P = 0.605), as were leak volumes. No significant PaO(2) difference was observed between the two groups at 1 h after satisfactory i-gel insertion (215 ± 38 vs. 222 ± 54; P = 0.502). CONCLUSIONS: The use of an i-gel during PEEP application at 5 cmH(2)O did not increase the incidence of a significant air leak, and a PEEP of 5 cmH(2)O failed to improve arterial oxygenation during controlled ventilation in healthy adult patients

EST sequencing and gene expression profiling in Scutellaria baicalensis

Scutellaria baicalensis is an important medicinal plant, but few genomic resources are available for this species, as well as for other non-model plants. One of the major new directions in genome research is to discover the full spectrum of genes transcribed from the whole genome. Here, we report extensive transcriptome data of the early growth stage of S. baicalensis. This transcriptome consensus sequence was constructed by de novo assembly of shotgun sequencing data, obtained using multiple next-generation DNA sequencing (NGS) platforms (Roche/454 GS_FLX+ and Illumina/Solexa HiSeq2000). We show that this new approach to obtain extensive mRNA is an efficient strategy for genome-wide transcriptome analysis. We obtained 1,226,938 and 161,417,646 reads using the GS_FLX and the Illumina/Solexa HiS-eq2000, respectively. De novo assembly of the high-quality GS_FLX and Illumina reads (95 % and 75 %) resulted in more than 82 Mb of mRNA consensus sequence, which we assembled into 51,188 contigs, with at least 500 bp per contig. Of these contigs, 39,581 contained known genes, as determined by BLASTX searches against non-redundant NCBI database. Of these, 20,498 different genes were expressed during the early growth stage of S. baicalensis. We have made the expressed sequences available on a public database. Our results demonstrate the utility of combining NGS technologies as a basis for the development of genomic tools in non-model, medicinal plant species. Knowledge of all described genes and quantitation of the expressed genes, including the transcription factors involved, will be useful in studies of the biology of S. baicalensis gene regulation

Comparison of once-daily versus twice-daily combination of Ropinirole prolonged release in Parkinson¿s disease

Trial registration : This study is registered with ClinicalTrials.gov, number NCT00986245.Background : Ropinirole prolonged release (RPR) is a once-daily formulation. However, there may be individual pharmacokinetic differences so that multiple dosing may be preferred in some individuals. This study compares once-daily and twice-daily RPR in patients with Parkinsons disease. Methods : This study was an open-label crossover study. We enrolled Parkinsons disease patients on dopamine agonist therapy with unsatisfactory control such as motor fluctuation, dyskinesia and sleep-related problems. Agonists were switched into equivalent dose of RPR. Subjects were consecutively enrolled into either once-daily first or twice-daily first groups, and received the same amount of RPR in a single and two divided dosing for 8 weeks respectively in a crossover manner without a washout period. The primary outcome was a questionnaire of the preference completed by patients in the last visit. The secondary outcome measures included the Unified Parkinsons Disease Rating Scale part 3 (mUPDRS), Hoehn and Yahr stage (H&Y); sleep questionnaire including overall quality of sleep, nocturnal off symptoms and early morning symptoms; Epworth Sleep Scale (ESS); compliances and patient global impression (PGI). Results : A total of 82 patients were enrolled and 61 completed the study. 31 patients preferred twice-daily regimen, 17 preferred the once-daily regimen, and 13 had no preference. Their mean mUPDRS, H&Y, ESS, sleep quality, compliance and adverse events were not statistically different in both regimens. PGI-improvement on wearing off defined was better in twice-daily dosing regimen. Conclusions : RPR is a once-daily formulation, but multiple dosing was preferred in many patients. Multiple dosing of RPR might be a therapeutic option if once-daily dosing is unsatisfactory.This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (A101273, BSJ).Peer Reviewe