Attitudes toward COVID-19 vaccines in Chinese college students

Background: Vaccination is an important preventative measure against the coronavirus disease 19 (COVID-19) pandemic. To implement vaccination and immunization programs effectively, it is essential to investigate public attitudes toward COVID-19 vaccines. This study examined the attitudes of Chinese college students toward COVID-19 vaccines and their associated factors. Methods: A cross-sectional study was conducted in college students nationwide from December 27, 2020 to January 18, 2021. Attitudes toward COVID-19 vaccines and acceptance of future vaccination programs were assessed. Results: Totally, 2,881 college students participated in this survey; of them, 76.3% (95% CI: 74.8% - 77.9%) were willing to accept a COVID-19 vaccine in the future. Multiple logistic analysis revealed that students living in urban (OR=1.409, 95% CI: 1.152 - 1.724, p=0.001) and those studying health-related courses (OR=1.581, 95% CI: 1.291 - 1.935, p<0.001) were more likely to have a positive attitude toward COVID-19 vaccines. In addition, those who were worried about being infected with COVID-19 (very much vs no, OR=1.690, 95% CI: 1.212-2.356, p=0.002), heard previously about COVID-19 vaccines (OR=1.659, 95% CI: 1.268-2.170, p<0.001), believed that vaccines are safe (Yes vs No, OR=3.570, 95% CI: 1.825-6.980), thought that vaccines can protect people from being infected with COVID-19 (Yes vs No, OR=1.957, 95% CI: 1.286-2.979, p=0.002), and had encouraged their family and friends to have a vaccine (Yes vs No, OR=17.745, 95% CI: 12.271-25.660, p<0.001) had higher acceptance of COVID-19 vaccination. Conclusions: A high rate of acceptance of COVID-19 vaccines was found among Chinese college students. However, vaccine uptake may be reduced by concerns about vaccine safety and efficacy. Alleviating these concerns and enhancing public confidence in vaccines are crucial for future immunization programs against the COVID-19 pandemic.     

Expression of Aeromonas caviae polyhydroxyalkanoate synthase gene in Burkholderia sp. USM (JCM15050) enables the biosynthesis of SCL-MCL PHA from palm oil products

AIMS: Burkholderia sp. USM (JCM15050) isolated from oil-polluted wastewater is capable of utilizing palm oil products and glycerol to synthesize poly(3-hydroxybutyrate) [P(3HB)]. To confer the ability to produce polymer containing 3-hydroxyhexanoate (3HHx), plasmid (pBBREE32d13) harbouring the polyhydroxyalkanoate (PHA) synthase gene of Aeromonas caviae (phaC(Ac)) was transformed into this strain. Methods and Results: The resulting transformant incorporated approximately 1 ± 0·3 mol% of 3HHx in the polymer when crude palm kernel oil (CPKO) or palm kernel acid oil was used as the sole carbon source. In addition, when the transformed strain was cultivated in the mixtures of CPKO and sodium valerate, PHA containing 69 mol% 3HB, 30 mol% 3-hydroxyvalerate and 1 mol% 3HHx monomers was produced. Batch feeding of carbon sources with 0·5% (v/v) CPKO at 0 h and 0·25% (w/v) sodium valerate at 36 h yielded 6 mol% of 3HHx monomer by controlled-feeding strategies. CONCLUSIONS: Burkholderia sp. USM (JCM15050) has the metabolic pathways to supply both the short-chain length (SCL) and medium-chain length (MCL) PHA monomers. By transforming the strain with the Aer. caviae PHA synthase with broader substrate specificity, SCL-MCL PHA was produced. Significance and Impact of the Study: This is the first study demonstrating the ability of transformant Burkholderia to produce P(3HB-co-3HHx) from a single carbon source.     

DNA accelerates the inhibition of human cathepsin V by serpins

A balance between proteolytic activity and protease inhibition is crucial to the appropriate function of many biological processes. There is mounting evidence for the presence of both papain-like cysteine proteases and serpins with a corresponding inhibitory activity in the nucleus. Well characterized examples of cofactors fine tuning serpin activity in the extracellular milieu are known, but such modulation has not been studied for protease-serpin interactions within the cell. Accordingly, we present an investigation into the effect of a DNA-rich environment on the interaction between model serpins (MENT and SCCA-1), cysteine proteases (human cathepsin V and human cathepsin L), and cystatin A. DNA was indeed found to accelerate the rate at which MENT inhibited cathepsin V, a human orthologue of mammalian cathepsin L, up to 50-fold, but unexpectedly this effect was primarily effected via the protease and secondarily by the recruitment of the DNA as a "template" onto which cathepsin V and MENT are bound. Notably, the protease-mediated effect was found to correspond both with an altered substrate turnover and a conformational change within the protease. Consistent with this, cystatin inhibition, which relies on occlusion of the active site rather than the substrate-like behavior of serpins, was unaltered by DNA. This represents the first example of modulation of serpin inhibition of cysteine proteases by a co-factor and reveals a mechanism for differential regulation of cathepsin proteolytic activity in a DNA-rich environment.     

Amyloid Precursor Protein Enhances Nav1.6 Sodium Channel Cell Surface Expression

Amyloid precursor protein (APP) is commonly associated with Alzheimer disease, but its physiological function remains unknown. Nav1.6 is a key determinant of neuronal excitability in vivo. Because mouse models of gain of function and loss of function of APP and Nav1.6 share some similar phenotypes, we hypothesized that APP might be a candidate molecule for sodium channel modulation. Here we report that APP colocalized and interacted with Nav1.6 in mouse cortical neurons. Knocking down APP decreased Nav1.6 sodium channel currents and cell surface expression. APP-induced increases in Nav1.6 cell surface expression were G_o protein-dependent, enhanced by a constitutively active G_o protein mutant, and blocked by a dominant negative G_o protein mutant. APP also regulated JNK activity in a G_o protein-dependent manner. JNK inhibition attenuated increases in cell surface expression of Nav1.6 sodium channels induced by overexpression of APP. JNK, in turn, phosphorylated APP. Nav1.6 sodium channel surface expression was increased by T668E and decreased by T668A, mutations of APP695 mimicking and preventing Thr-668 phosphorylation, respectively. Phosphorylation of APP695 at Thr-668 enhanced its interaction with Nav1.6. Therefore, we show that APP enhances Nav1.6 sodium channel cell surface expression through a G_o-coupled JNK pathway.     

Genetic mapping and comparative analysis of seven mutants related to seed fiber development in cotton

Mapping of genes that play major roles in cotton fiber development is an important step toward their cloning and manipulation, and provides a test of their relationships (if any) to agriculturally-important QTLs. Seven previously identified fiber mutants, four dominant (Li ₁, Li ₂, N ₁ and Fbl) and three recessive (n ₂, sma-4(h _a), and sma-4(fz)), were genetically mapped in six F₂ populations comprising 124 or more plants each. For those mutants previously assigned to chromosomes by using aneuploids or by linkage to other morphological markers, all map locations were concordant except n ₂, which mapped to the homoeolog of the chromosome previously reported. Three mutations with primary effects on fuzz fibers (N ₁, Fbl, n ₂) mapped near the likelihood peaks for QTLs that affected lint fiber productivity in the same populations, perhaps suggesting pleiotropic effects on both fiber types. However, only Li ₁ mapped within the likelihood interval for 191 previously detected lint fiber QTLs discovered in non-mutant crosses, suggesting that these mutations may occur in genes that played early roles in cotton fiber evolution, and for which new allelic variants are quickly eliminated from improved germplasm. A close positional association between sma-4(h _a ), two leaf and stem-borne trichome mutants (t ₁ , t ₂), and a gene previously implicated in fiber development, sucrose synthase, raises questions about the possibility that these genes may be functionally related. Increasing knowledge of the correspondence of the cotton and Arabidopsis genomes provides several avenues by which genetic dissection of cotton fiber development may be accelerated.     

A population-based LD map of the human chromosome 6p

The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human–mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits. Electronic supplementary material Electronic supplementary material is available for this article at and accessible for authorised users. H. Yu and J.-M. Chia should be regarded as joint first authors.     

The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine

Anthracyclines remain a mainstay of chemotherapy in spite of their well-recognized cardiotoxicity. Recent experience with trastuzumab (Herceptin) and anthracycline therapy has prompted a detailed analysis of the function of erbB2 in the heart. These studies demonstrate a cardioprotective effect of neuregulin, the endogenous ligand for the erbB4/erbB2 heterodimeric receptor complex. Although the mechanisms of cytoprotection remain incompletely understood, these studies have triggered the question of whether physiological manipulation of cardioprotective pathways that involve erbB can be used to improve outcome in patients treated with anthracyclines. The local activation of cardioprotection by cardiovascular exercise may be such a manipulation and warrants further investigation.     

A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II

Etoposide is a widely used anticancer drug that targets topoisomerase II, an essential nuclear enzyme. However, despite the fact that it has been in use and studied for more than 30 years the specific site on the enzyme to which it binds is unknown. In order to identify the etoposide binding site(s) on topoisomerase II, a diazirine-based photoaffinity etoposide analog probe has been synthesized and its photoreactivity and biological activities have been characterized. Upon UV irradiation, the diazirine probe rapidly produced a highly reactive carbene species that formed covalent adducts containing stable carbon-based bonds indicating that it should also be able to form stable covalent adducts with amino acid residues on topoisomerase II. The human leukemia K562 cell growth and topoisomerase II inhibitory properties of the diazirine probe suggest that it targets topoisomerase II in a manner similar to etoposide. The diazirine probe was also shown to act as a topoisomerase II poison through its ability to cause topoisomerase IIα-mediated double-strand cleavage of DNA. Additionally, the diazirine probe significantly increased protein–DNA covalent complex formation upon photoirradiation of diazirine probe-treated K562 cells, as compared to etoposide-treated cells. This result suggests that the photoactivated probe forms a covalent adduct with topoisomerase IIα. In conclusion, the present characterization of the chemical, biochemical, and biological properties of the newly synthesized diazirine-based photoaffinity etoposide analog indicates that use of a proteomics mass spectrometry approach will be a tractable strategy for future identification of the etoposide binding site(s) on topoisomerase II through covalent labeling of amino acid residues.