ESL Club & Women Speak: Our Second Home in America

SWOSU ESL Club Newsletter: Fall 2017 is the third issue of the newsletter for the English as a Second Language Club (ESL).https://dc.swosu.edu/esl/1002/thumbnail.jp

Mechanism for controlling the monomer–dimer conversion of SARS coronavirus main protease

[[abstract]]The Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (Mpro) cleaves two virion polyproteins (pp1a and pp1ab); this essential process represents an attractive target for the development of anti-SARS drugs. The functional unit of Mpro is a homodimer and each subunit contains a His41/Cys145 catalytic dyad. Large amounts of biochemical and structural information are available on Mpro; nevertheless, the mechanism by which monomeric Mpro is converted into a dimer during maturation still remains poorly understood. Previous studies have suggested that a C-terminal residue, Arg298, interacts with Ser123 of the other monomer in the dimer, and mutation of Arg298 results in a monomeric structure with a collapsed substrate-binding pocket. Interestingly, the R298A mutant of Mpro shows a reversible substrate-induced dimerization that is essential for catalysis. Here, the conformational change that occurs during substrate-induced dimerization is delineated by X-ray crystallography. A dimer with a mutual orientation of the monomers that differs from that of the wild-type protease is present in the asymmetric unit. The presence of a complete substrate-binding pocket and oxyanion hole in both protomers suggests that they are both catalytically active, while the two domain IIIs show minor reorganization. This structural information offers valuable insights into the molecular mechanism associated with substrate-induced dimerization and has important implications with respect to the maturation of the enzyme.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子

Association of ORAI1 Haplotypes with the Risk of HLA-B27 Positive Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility. We carried out a case-control study to determine whether the genetic polymorphisms of ORAI1 gene, a major component of store-operated calcium channels that involved the regulation of immune system, is a susceptibility factor to AS in a Taiwanese population. We enrolled 361 AS patients fulfilled the modified New York criteria and 379 controls from community. Five tagging single nucleotides polymorphisms (tSNPs) at ORAI1 were selected from the data of Han Chinese population in HapMap project. Clinical statuses of AS were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Index (BAS-G). Our results indicated that subjects carrying the minor allele homozygote (CC) of the promoter SNP rs12313273 or TT homozygote of the SNP rs7135617 had an increased risk of HLA-B27 positive AS. The minor allele C of 3′UTR SNP rs712853 exerted a protective effect to HLA-B27 positive AS. Furthermore, the rs12313273/rs7135617 pairwise allele analysis found that C-G (OR 1.69, 95% CI 1.27, 2.25; p = 0.0003) and T-T (OR 1.75, 95% CI 1.36, 2.27; p<0.0001) haplotypes had a significantly association with the risk of HLA-B27-positive AS in comparison with the T-G carriers. This is the first study that indicate haplotypes of ORAI1 (rs12313273 and rs7135617) are associated with the risk of HLA-B27 positive AS

The mediating role of psychological well-being in the relationship between self-care knowledge and disease self-management in patients with hypertensive nephropathy

[[abstract]]Objective: This study aimed to investigate the correlation between self-care knowledge, psychological well-being, and disease self-management in patients with hypertensive nephropathy, and to assess the effect of psychological well-being as a mediator of self-care knowledge and disease self-management. Methods: This is a cross-sectional study. The 220 patients with hypertensive nephropathy were recruited from a teaching hospital in Taiwan using purposive sampling. The average age was 70.14 (SD = 11.96) years old. Among them, 128 (58.2%) were male and 92 (41.8%) were female. Instruments included a hypertensive nephropathy self-care knowledge scale, the World Health Organization-5 Well-Being Index, and the chronic kidney disease self-management instrument. The mediating effect was determined with linear regression models and the Sobel test. Results: The total explanatory variation of age, systolic blood pressure, psychological well-being, and self-care knowledge on the disease self-management was 27.7%. Psychological well-being was the most important explanatory factor and alone explains 16%. Psychological well-being was a partial mediator of self-care knowledge and quality of life in patients with hypertensive nephropathy, with a total effect of 23.2%. Conclusions: This study showed that older patients with hypertensive nephropathy and those with a higher systolic blood pressure had lower levels of disease self-management. The higher the patients' self-care knowledge and psychological well-being, the better their disease self-management

Universal ferroelectric switching dynamics of vinylidene fluoride-trifluoroethylene copolymer films

In this work, switching dynamics of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer films are investigated over unprecedentedly wide ranges of temperature and electric field. Remarkably, domain switching of copolymer films obeys well the classical domain nucleation and growth model although the origin of ferroelectricity in organic ferroelectric materials inherently differs from the inorganic counterparts. A lower coercivity limit of 50 MV/m and 180° domain wall energy of 60 mJ/m2 are determined for P(VDF-TrFE) films. Furthermore, we discover in copolymer films an anomalous temperature-dependent crossover behavior between two power-law scaling regimes of frequency-dependent coercivity, which is attributed to the transition between flow and creep motions of domain walls. Our observations shed new light on the switching dynamics of semi-crystalline ferroelectric polymers, and such understandings are critical for realizing their reliable applications.Published versio

Rapid HPLC Quantification Approach for Detection of Active Constituents in Modern Combinatorial Formula, San-Huang-Xie-Xin-Tang (SHXXT)

San-Huang-Xie-Xin-Tang (SHXXT), one of the most important traditional Chinese medicinal formulas, is comprised by three herbal medicines, the rhizome of Rheum officinale [or R. tanguticum (Polygonaceae) (Dahuang in Chinese)], the root of Scutellaria baicalensis (Labiatae) (Huangqin in Chinese), and the rhizome of Coptis chinensis (Ranunculaceae) (Huanglian in Chinese) in the ratios of 2:1:1 or 1:1:1. This study is aimed to quantitate and qualify of SHXXT, by a rapid, convenient, and effective HPLC-PDA approach associated with LC-MS technique. Of which method, nine chosen major bioactive components in SHXXT, including aloe-emodin (Ale), baicalin (Ba), berberine (Be), coptisine (Co), palmatine (Pa), resveratroloside (Res), rhein (Rh), sennoside A (Se-A), and wogonin (Wo), were evaluated within 30 minutes. The nine chemical markers were monitored in a high sensitivity with a low detection limit of 0.01‒0.55 μg/mL and the correlation coefficient of the regression curve revealed a good linearity with R2 > 0.99. Moreover, the extraction solution system and the HPLC elution conditions were also optimized in the present study. This present developed protocol was then successfully applied to quantify nine chemical markers of ten SHXXT products from eight Taiwanese TCM pharmaceutical companies. In quantitative results, Res was found as the major compound in SHXXT-1~5 & 8 with significantly higher amounts than those in other products, indicating the products SHXXT-1~5 & 8 may use R. tanguticum as the raw material, which possessed a higher concentration of the bioactive composition Res, instead of R. officinale. Simultaneously, Ale, Rh, and Wo were less than 2% in these ten products. Different chemical profiles of commercial products indicated that, probably, each product with the same named formula might be regarded as a sole medicine and need to be investigated individually. Importantly, it is never too much to emphasize the importance of quality control in TCM development

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3‐induced mitophagy

Abstract Neuroblastoma is the second most common pediatric malignancy and has a high rate of spontaneous remission. Uncovering the mechanisms underlying neuroblastoma cell differentiation is critical for therapeutic purposes. A neuroblastoma cell line (N2a) treated with either serum withdrawal (0.1 nmol/L) for 24 hours was used as a cell differentiation research model. Interestingly, the hyaluronan synthase 3 (HAS3) protein was induced in differentiated N2a cells. N2a‐allografted nude mice received an intraperitoneal injection of melatonin (40 or 80 mg/kg/day for 3 weeks). The mean tumor volume in mice treated with 80 mg/kg melatonin was smaller than that in PBS‐treated mice (1416.3 and 3041.3 mm3, respectively, difference = 1625 mm3, *P = 0.0003, n = 7 per group). Compared with the vector control group, N2a cells with forced HAS3 overexpression showed significantly increased neuron length (*P = 0.00082) and neurite outgrowth (*P = 0.00059). Intracellular changes in autophagy, including distorted mitochondria with abnormal circular inner membranes, were detected by transmission electron microscopy (TEM). Our study demonstrated that HAS3‐mediated signaling activated by physiological concentrations of melatonin (>0.1 nmol/L) triggered significant N2a cell differentiation. These results provide molecular data with potential clinical relevance for therapeutic drug development

Type-3 Hyaluronan Synthase Attenuates Tumor Cells Invasion in Human Mammary Parenchymal Tissues

The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic