DataSheet_1_Cytokine IL-5 and HGF: combined prediction of non-/low immune response to hepatitis B vaccination at birth in infants born to HBsAg-positive mothers.docx

BackgroundThe immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential.Methods100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed.ResultsWe found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844.ConclusionThe present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.</p

Association rate, dissociation rate, and equilibrium dissociation constants of Trn1 and wild-type and mutant FUS-NLS.

<p>The 12 ALS mutations are organized in the order of decreasing affinity.</p>a<p>The relative affinity is defined as <i>K</i>_D of WT (M) divided by <i>K</i>_D of the FUS-NLS mutants <i>(</i>M<i>).</i></p><p>The correlation coefficient χ² value is a statistical measure of how closely the fitted curve fits the experimental data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047056#pone.0047056-Imasaki1" target="_blank">[15]</a> (see Methods).</p

The structure of the FUS-NLS/Trn1 complex.

<p>(A) The overall structure. (B) The 2<i>F_o</i> − <i>F_c</i> composite omit electron density map around the FUS-NLS fragment (residues 508–526) contoured at 1.0 σ (gray mesh). The Trn1 and the FUS-NLS are shown in cyan and yellow, respectively. (C) The superimposition of residues 508–526 of FUS-NLS (yellow; PDB code: 4FQ3) with the corresponding regions from hnRNP A1-NLS (blue; PDB code: 2H4M), hnRNP D-NLS (grey; PDB code: 2Z5N), hnRNP M-NLS (magenta; PDB code: 2OT8), and TAP-NLS (cyan; PDB code: 2Z5K). The α-helix is unique in FUS-NLS whereas no specific secondary structure was found in the other structures.</p

Subcellular localization of WT and mutant FUS.

<p>GFP-tagged WT full-length human FUS or different ALS mutants (S513P, G515C, R521G, R522G and P525L) were transfected into N2a cells. The cells were fixed in 4% paraformaldehyde and permeabilized by 0.1% Triton X-100 24 hours after transfection. The nuclei were stained by 4′,6-diamidino-2-phenylindole (DAPI). The coverslips were mounted and images were acquired using an Olympus confocal microscope (Olympus Fluoview, Ver.1.7c).</p

Multifunctional Electrochemical Platforms Based on the Michael Addition/Schiff Base Reaction of Polydopamine Modified Reduced Graphene Oxide: Construction and Application

In this paper, a new strategy for the construction of multifunctional electrochemical detection platforms based on the Michael addition/Schiff base reaction of polydopamine modified reduced graphene oxide was first proposed. Inspired by the mussel adhesion proteins, 3,4-dihydroxyphenylalanine (DA) was selected as a reducing agent to simultaneously reduce graphene oxide and self-polymerize to obtain the polydopamine-reduced graphene oxide (PDA-rGO). The PDA-rGO was then functionalized with thiols and amines by the reaction of thiol/amino groups with quinine groups of PDA-rGO via the Michael addition/Schiff base reaction. Several typical compounds containing thiol and/or amino groups such as 1-[(4-amino)­phenylethynyl] ferrocene (Fc-NH₂), cysteine (cys), and glucose oxidase (GOx) were selected as the model molecules to anchor on the surface of PDA-rGO using the strategy for construction of multifunctional electrochemical platforms. The experiments revealed that the composite grafted with ferrocene derivative shows excellent catalysis activity toward many electroactive molecules and could be used for individual or simultaneous detection of dopamine hydrochloride (DA) and uric acid (UA), or hydroquinone (HQ) and catechol (CC), while, after grafting of cysteine on PDA-rGO, simultaneous discrimination detection of Pb²⁺ and Cd²⁺ was realized on the composite modified electrode. In addition, direct electron transfer of GOx can be observed when GOx-PDA-rGO was immobilized on glassy carbon electrode (GCE). When glucose was added into the system, the modified electrode showed excellent electric current response toward glucose. These results inferred that the proposed multifunctional electrochemical platforms could be simply, conveniently, and effectively regulated through changing the anchored recognition or reaction groups. This study would provide a versatile method to design more detection or biosensing platforms through a chemical reaction strategy in the future

The interactions between the Trn1 and the FUS-NLS.

<p>(A) Summary of the polar/electrostatic interactions between FUS-NLS (yellow) and Trn1 (cyan). FUS-NLS is divided into region I (E523–Y526), region II (D512–R522), and region III (P508–M511). (B) Schematic illustration of the hydrophobic contacts between the region I of FUS-NLS (E523–R524–P525–Y526) and Trn1. (C) Schematic illustration of the hydrophobic contacts between the region III of FUS-NLS (P508–G509–K510–M511) and Trn1. (D). The interaction between R524 and Q519, D520 and R522 within FUS-NLS. The figure is prepared with LIGPLOT <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047056#pone.0047056-Wallace1" target="_blank">[38]</a>.</p

Correlation between the disease duration of familial ALS patients carrying R518K, R521G, R524S and P525L mutations and the relative binding affinity of the mutant proteins to Trn1.

<p>The coefficient of determination R² is 0.88, suggesting strong correlation. The number of patients for the R518K, R521G, R524S and P525L mutations are 12, 4, 2, and 8, respectively.</p

Sequence analysis of FUS-NLS.

<p>(A). Domain structure of FUS with the C-terminal NLS. The ALS mutations are clustered in the NLS and the mutations studied here are shown in red. (B) Amino acid sequence alignments of FUS-NLS with other PY NLS’s from hnRNP A1, hnRNP D, hnRNP M and TAP. (C). Sequence alignment of FUS-NLS from different organisms.</p

Perceptions about respiratory syncytial virus (RSV) and attitudes toward the RSV vaccine among the general public in China: A cross-sectional survey

Our study aims to assess the public’s perceptions of respiratory syncytial virus (RSV) and attitudes toward the RSV vaccine and to identify associated factors in China. A nationwide cross-sectional survey conducted using an online platform between August 16 and September 14, 2023. Questions related to socio-demographics, awareness, knowledge, perceptions of susceptibility and severity of RSV, and attitudes toward the RSV vaccine were included in the questionnaire. We used the chi-square test and logistic regression model to explore the associated factors. Overall, 2133 individuals were included in this study. Nearly a quarter of participants (24.3%) indicated that they had never heard of RSV. The proportion of individuals aged over 50 years reporting never having heard of RSV (36.5%) and having a low knowledge level of RSV (55.3%) was significantly higher that of other younger age groups. More than half of individuals (55.7%) exhibited low level of perceptions of susceptibility concerning RSV infection. A total of 68.4% of the participants expressed willingness to receive the RSV vaccine. Younger age was positively associated with a higher willingness to be vaccinated. The most frequent reason for declining the vaccine was “Concern about vaccine’s safety or side effects.” About 60% of individuals considered a price of RSV vaccine below 200 CNY (28 USD) as acceptable. The awareness and perceived susceptibility to RSV infection were limited to the Chinese public. It is necessary to take measures to address the low awareness and knowledge of RSV and acceptability of the RSV vaccine among older adults.</p

Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment

<p>Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood–brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms <i>in vivo</i> and <i>in vitro</i>. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.</p