Dual-mRNA Delivery Using Tumor Cell Lysate-Based Multifunctional Nanoparticles as an Efficient Colon Cancer Immunogene Therapy.

Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.

Examining First- and Second-Level Digital Divide at the Intersection of Race/Ethnicity, Gender, and Socioeconomic Status: An Analysis of the National Health and Aging Trends Study.

BACKGROUND AND OBJECTIVES: Significant societal and technological changes in the 2010s called for an up-to-date understanding of the digital divide among older adults in the United States. This trend study aimed to examine the effects of race/ethnicity and the intersecting effects of race/ethnicity with other marginalized identities related to gender, income, education, and occupation on the first- and second-level digital divide. RESEARCH DESIGN AND METHODS: Utilizing a nationally representative sample of older community dwellers from the National Health and Aging Trends Study, we conducted weighted logistic regressions at 3 time points (2011/2013, 2015, and 2019). The first-level digital divide was measured by access to working phones or computers/laptops; the second-level divide was measured by 7 activities in personal task, social, and health-related Internet use. RESULTS: The first-level racial/ethnic digital divide became nonsignificant in 2019, whereas the disparities in all second-level measures persisted. The intersecting effects of race/ethnicity with low education and/or low income became nonsignificant in 2019 for personal-task use. However, the interactions with low education and/or low income became significant for social and health-related use in 2015 and/or 2019. DISCUSSION AND IMPLICATIONS: This study highlights the persistence of the second-level racial/ethnic digital divide among older community dwellers in the United States, especially the exacerbated social and health-related digital divide for people of color with low socioeconomic status. By considering intersections of marginalized social identities, policymakers and stakeholders should develop targeted strategies to bridge the digital divide, promote health outcomes, and reduce health disparities.

Older adults' online activities and cognition: Investigating the psychological mechanisms and age and gender differences.

OBJECTIVES: This study aimed to investigate psychological mechanisms underlying the association between older adults' Internet use and cognition and examine potential age and gender group differences. METHODS: 2064 older participants were extracted from the Waves 2012, 2013, and 2016 Health and Retirement Study. Internet use was measured by two sets of variables: Internet access and different types of online activities (i.e., informational use, social use, online shopping, and online banking). Path analyses were applied to test the proposed mechanisms via three mediators (i.e., loneliness, depressive symptoms, and perceived control). Multi-group analyses were conducted to examine the potential group differences. RESULTS: Internet use was positively associated with cognition. Despite the large direct effect, small but significant indirect effects via depressive symptoms and perceived control were identified across all online activities. Multi-group analyses revealed age-group differences in the mechanisms: depressive symptoms mediated the effects of all online activities on cognition among young-old adults, while perceived control mediated all the effects among old-old adults. Gender group differences were also identified: depressive symptoms mediated the effects of all online activities on cognition among older women and most online activities among older men, whereas perceived control mediated the associations between informational and instrumental (i.e., online shopping and banking) use and cognition among older men. DISCUSSION: This study highlights the mediating effect of depressive symptoms and perceived control and age and gender differences regarding the Internet use-cognition association. Internet-based cognitive interventions should consider these psychological mediators and age and gender differences for the best results.

Regulation of Burkholderia cenocepacia virulence by the fatty acyl-CoA ligase DsfR as a response regulator of quorum sensing signal.

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Bridging the Access Gap: A Decade of Narrowing the Digital Divide for Hispanic Older Adults in the United States.

Objectives: This study examines the digital divide between Hispanic and non-Hispanic White older adults in the United States from 2011 to 2021, using an intersectionality perspective. Methods: Eleven waves of data from the National Health and Aging Trend were analyzed through multilevel logistic regression, focusing on the intersection between race/ethnicity and time (measured by survey waves) within gender, education, and income subgroups. The digital divide was measured by Internet access. Results: Despite the enduring digital access gap, the longitudinal analysis revealed a narrowing digital divide between Hispanic and non-Hispanic White older adults, especially those with low education and income. Discussion: The observed trend signifies progress in digital inclusivity initiatives yet highlights ongoing challenges in fully bridging the divide for the Hispanic older adult community. Future efforts should not only focus on access but also on enhancing the effective usage of digital technologies to promote health equity and well-being.

Intra- and inter-rater reliability of muscle and fat thickness measurements obtained using portable ultrasonography in older adults.

BACKGROUND & AIMS: Ultrasonography (US) is a promising tool for assessing body composition, offering accuracy and accessibility. However, technician skills and equipment characteristics can impact measurement reliability. We aimed to evaluate the intra- and inter-rater reliability of two evaluators using A-mode Portable Ultrasound to measure muscle and fat thickness in Brazilian older adults. METHODS: Quantitative cross-sectional study carried out with 150 community-dwelling older adults of Campinas-SP-Brazil, recruited in a retirement preparation program and a geriatric outpatient care unit. Scans of nine anatomical points were performed using the portable ultrasound in A-mode (BodyMetrix Pro System BX2000; Livermore, CA), with 6 scans per location and 3 measurements taken by each evaluator. After the selection and analysis of the generated images, muscle and fat thickness were measured. Reliability estimates between measures of the same evaluator (intra-rater) and between evaluators (inter-rater) were assessed using intraclass correlation coefficients (ICC), and differences within and between technicians were assessed using one-way ANOVA. Analyses were carried out for the overall sample and stratified by sex and by nutritional status. RESULTS: Excellent ICC values (>0.90) were found for subcutaneous fat thickness in intra- and inter-rater reliability analyses. The lowest ICC values were observed for deep abdominal fat thickness measured by evaluator 1 (ICC = 0.90) and evaluator 2 (ICC = 0.87), as well as in the inter-rater analysis (ICC = 0.85). Muscle thickness measurements had satisfactory ICC values for triceps, biceps, anterior thigh, and calf, ranging from moderate to good (ICC 0.50-0.90). CONCLUSION: A portable A-mode ultrasound demonstrates excellent reliability among both intra- and inter-raters for assessing fat thickness but only moderate for muscle thickness in older adults. Hence, this could prompt inquiries regarding the sole reliance on this tool for quantifying muscle mass and examining sarcopenia in older adults. To our knowledge, this study represents the first assessment of reliability for a portable A-mode ultrasound device conducted with older adults.