Assessment of activity and mechanism of action of β-Dglucan against dengue virus

Purpose: To assess the antiviral efficiency of β-D-glucan (BDG) on human liver cell line (WRL68) infected with dengue virus (DENV).Methods: Cytotoxic activity was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Solid-phase virus binding assay was used to determine the presence of a chemical affinity between dengue virus type 2 (DENV-2) and BDG. Plaque formation assay was performed to measure the suppression of DENV-2.Results: Plaque formation assay results revealed that the inhibition of DENV infection by BDG was effective at 400 μg/mL which occurred by inhibiting virus replication. BDG inhibited DENV replication and produced minimal toxicity on WRL68 cells at 600 μg/mL in a concentration-dependent manner. Treatment of DENV-2 with the highest concentration of the BDG resulted in 60, 55, and 50 % viability at 24, 48, and 72 h, respectively. Plaque formation and binding efficiency data confirmed that BDG protected the WRL68 cells against DENV-2.Conclusion: The results indicate that in infected cells, β-D-glucan was found to be potent in inhibiting replication of the dengue virus.Keywords: Dengue, β-D-glucan, Polysaccharide, Antiviral, Plaque formation, Binding efficienc

Metagenomic insights into the abundance and composition of resistance genes in aquatic environments:Influence of stratification and geography

A global survey was performed with 122 aquatic metagenomic DNA datasets (92 lake water and 30 seawater) obtained from the Sequence Read Archive (SRA). Antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) were derived from the dataset sequences via bioinformatic analysis. The relative abundances of ARGs and MRGs in lake samples were in the ranges ND (not detected)-1.34x10(0) and 1.22x10(-3) -1.98x10(-1) copies per 16S rRNA, which were higher than those in seawater samples. Among ARGs, multidrug resistance genes and bacitracin resistance genes had high relative abundances in both lake and sea water samples. Multimetal resistance genes, mercury resistance genes and copper resistance genes had the greatest relative abundance for MRGs. No significant difference was found between epilimnion and hypolimnion in abundance or the Shannon diversity index for ARGs and MRGs. Principal coordinates analysis and permutational multivariate analysis of variance (PERMANOVA) test showed that stratification and geography had significant influence on the composition of ARGs and MRGs in lakes (p < 0.05, PERMANOVA). Coastal seawater samples had significantly greater relative abundance and a higher Shannon index for both ARGs and MRGs than deep ocean and Antarctic seawater samples (p < 0.05, Kruskal-Wallis one-way ANOVA), suggesting that human activity may exert more selective pressure on ARGs and MRGs in coastal areas than those in deep ocean and Antarctic seawater

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles

Perceptions, behaviours and attitudes towards smoking held by the male partners of Chinese pregnant women:a qualitative study

Abstract Background Direct associations of tobacco exposure during pregnancy with pregnancy complications and adverse birth outcomes have been proven. Previous studies suggest that expecting a child provides a valuable opportunity to promote behavioural changes, such as smoking cessation, among the male partners of pregnant women. Thorough understandings of Chinese expectant fathers’ smoking behaviour during the transition to fatherhood is a prerequisite to the development of appropriate interventions to facilitate smoking cessation. This study aimed to explore the perceptions, behaviours and attitudes related to smoking among male partners of pregnant women in China. Methods A descriptive phenomenological approach was adopted. A purposive sample of expectant fathers aged 18 years or older who had a tobacco use history within the past year were recruited at obstetrics and gynaecology clinics and invited to participate in one-to-one, 20–30-min semi-structured interviews. The data analysis followed Colaizzi’s descriptive phenomenological method. Results Twenty-five expectant fathers were interviewed. Four themes were generated: 1) the benefits of smoking and respondents’ misperceptions of the impact of smoking and SHS and neglectful attitude of the impact of smoking, which were given as the major reasons for continuing to smoke; 2) factors contributing to smoking cessation, including concern for the potential health impact of continued smoking on the pregnant partner and baby, the role of being father, and the encouragement to quit from family members; and 3) perceived barriers to smoking cessation, including withdrawal symptoms or cigarette cravings, absence of smoking cessation support, and increasing stress. Conclusion This study provides a comprehensive understanding of the perception, behaviours, and attitudes related to smoking among Chinese expectant fathers. The findings of this study can guide healthcare professionals and policymakers in combining the distribution of educational information about the hazards of SHS for maternal and neonatal health with smoking cessation assistance for expectant fathers through policy initiatives and other types of incentives and programmes targeted to enhance smoking cessation among this population. Trial registration Prospectively registered at clinicaltrial.org ( NCT03401021 ) on 8 Jan 2018

The ion transporter Na⁺-K⁺-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis

The kidney is a comparatively hostile microenvironment characterized by highsodium concentrations; however, lymphocytes infiltrate and survive therein in autoimmune diseases such as lupus. The effects of sodium-lymphocyte interactions on tissue injury in autoimmune diseases and the mechanisms used by infiltrating lymphocytes to survive the highsodium environment of the kidney are not known. Here, we show that kidneyinfiltrating B cells in lupus adapt to elevated sodium concentrations and that expression of sodium potassium adenosine triphosphatase (Na+-K+-ATPase) correlates with the ability of infiltrating cells to survive. Pharmacological inhibition of Na+-K+-ATPase and genetic knockout of Na+-K+-ATPase γ subunit resulted in reduced B cell infiltration into kidneys and amelioration of proteinuria. B cells in human lupus nephritis biopsies also had high expression of Na+-K+-ATPase. Our study reveals that kidney-infiltrating B cells in lupus initiate a tissue adaption program in response to sodium stress and identifies Na+-K+-ATPase as an organ-specific therapeutic target

Prevention of dementia using mobile phone applications (PRODEMOS): A multinational, randomised, controlled effectiveness–implementation trial

Background: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. Methods: This open-label, blinded endpoint, hybrid effectiveness–implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55–75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12–18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed. Findings: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference –0·16, 95% CI –0·29 to –0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found. Interpretation: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up. Funding: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. Translation: For the Mandarin translation of the abstract see Supplementary Materials section

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38

BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.ConclusionA panel of BsAbs targeting CD38 and CD47 developed based on the “mAb-tarp” platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile

Accurate Inference of Local Phased Ancestry of Modern Admixed Populations

Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis

Needs and views on healthy lifestyles for the prevention of dementia and the potential role for mobile health (mHealth) interventions in China: A qualitative study

Objectives Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study. Design Qualitative semi-structured interview study, using thematic analysis. Setting Primary and secondary care in Beijing and Tai’an, China. Participants Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes. Results We performed 26 interviews with participants aged 55–86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional. Conclusions The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD