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Safety and contribution of elderly whole blood donors after raising the upper age limit: Hemovigilance data from a Chinese region from 2012 to 2023

Background In 2012, China raised the upper age restriction for blood donors from 55 to 60 years old. This study analyzed the impact of raising the upper age restriction on whole blood donor health, contribution to blood supply, and safety of blood. Methods The blood collection and donor hemovigilance data of the Chongqing Blood Center from 2012 to 2023 were analyzed to evaluate the safety of elderly blood donors. To evaluate the impact on blood donor and blood component safety, the number of blood donors and donations, the rate and causes of deferrals, donor health (vasovagal reaction risk), and the screening results of transfusion-transmitted infectious diseases of elderly blood donors (56–60 years) were compared to young blood donors (18–55 years). Results During the 12-year period, the proportion of elderly blood donors in whole blood donations increased 10-fold (0.19% to 1.89%), and the proportion of blood collections increased by the same factor (0.20% to 2.15%). Lower deferral rates were observed among older male donors compared to younger ones, whereas the reverse was found in females. A lower incidence of vasovagal reactions and positive HBV, HCV, and syphilis screening rates was found among male and female elderly blood donors compared to young blood donors. In contrast, the positive HIV reaction rate of older female donors was higher than that of young female blood donors. Conclusion This study finds an increasing frequency of donors aged 56–60. Deferral rates are lower among older male donors compared to young, but the reverse is seen in females. In addition, VVR rates and HCV, HBV and syphilis incidences are lower in old donors, but HIV rates appear highest among older donors.

Improving spaces for women first responders: A grounded theory on gender equity

Emergency response work has historically been performed by men and thus designed with them in mind; however, during the past few decades, increasing numbers of women are conducting this work. Despite growing participation, research suggests women first responders continue to face unsupportive workplace structures and cultures. This study explored the occupational experiences of women who work as firefighters, police officers, and paramedics from Southern Ontario, Canada. Semi-structured interviews conducted with this population (n = 20) focused on resiliency and stress, diversity and inclusion, and gender and the role of professional identity. Constructivist grounded theory guided analysis and cross-profession comparisons. Participants described significant improvements to women’s inclusion in first response work, however, they also identified continuing challenges. While some environments were described as highly supportive, many women still faced sexism and glass ceilings. Despite persisting obstacles, participants were deeply passionate about their work, and actively encouraged other women to join the field. Study results suggest that future advances can be encouraged by addressing the need for improved access to uniforms and equipment, on-the-job training to address barriers to promotions, flexible scheduling and childcare supports, and legislating equity, diversity, and inclusion training for all leaders and workers in the first responder community.

HLX and SLC25A20: Immunologic regulators bridging ankylosing spondylitis and uveitis via multi-omics integration and machine learning

Background Ankylosing spondylitis (AS), a chronic inflammatory disorder affecting axial joints, is frequently complicated by uveitis. However, the molecular mechanisms linking AS to secondary uveitis remain poorly understood. Methods We integrated transcriptomic datasets from AS (GSE73754) and uveitis (GSE194060) cohorts to identify shared molecular pathways. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO, SVM-RFE, random forest) were combined to prioritize biomarkers. Molecular docking was performed to evaluate drug-target interactions using Vina scores (≤−7 kcal/mol threshold). Results Cross-disease analysis revealed 697 overlapping dysregulated genes (481 upregulated, 216 downregulated), enriched in GTPase signaling and immune pathways. WGCNA identified disease-specific co-expression modules (AS: brown/tan modules, r = 0.39/0.35; uveitis: brown module, r = 0.49). Machine learning nominated HLX and SLC25A20 as core biomarkers, demonstrating robust diagnostic accuracy in discovery (AS AUC: 0.688/0.700; uveitis AUC: 0.867/0.838) and validation cohorts (AS AUC: 0.653/0.667; uveitis AUC: 0.662/0.736). Immune profiling linked HLX to neutrophil infiltration (r = 0.55, p < 0.01) and SLC25A20 to T helper cell regulation (r = 0.36, p < 0.01). Molecular docking identified high-affinity ligands for SLC25A20, including amiodarone (−8.0 kcal/mol) and estradiol (−7.7 kcal/mol), with folic acid showing dual binding potential (HLX: −7.5 kcal/mol; SLC25A20: −8.2 kcal/mol). Conclusion HLX and SLC25A20 emerge as immunologic regulators bridging AS and uveitis pathogenesis. These findings provide actionable targets for precision diagnostics and therapeutic development in AS-associated uveitis.

Global, regional, and national burdens of five main digestive system cancers in adolescents and young adults from 1990 to 2021 based on the Global Burden of Disease Study 2021: A cross-sectional study

Objective To evaluate the burden and trends of digestive system cancers in adolescents and young adults (AYAs) globally between 1990 and 2021. Methods Data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (1990–2021). We analyzed global, regional, and national disease burdens by calculating the age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) for AYAs. Joinpoint regression calculate the average annual percentage change (AAPC) in incidence, mortality, and DALYs for digestive system cancers in the AYAs. Decomposition analysis illustrate the impact of epidemiological changes, population growth, and population aging on the disease burden. Results Globally, the ASIR (AAPC: 0.37) of AYAs with colorectal cancer (CRC) showed an increasing trend, whereas the ASIR of AYAs with esophageal cancer (EC), gastric cancer (GC), pancreatic cancer (PC), and liver cancer (LC) showed a decreasing trend. The ASMR and age-standardized rates (ASR) of DALYs for all five types of digestive system cancers in AYAs also showed a decreasing trend. By gender, the ASIR for males has increased with an AAPC of 0.84. For the other four types of digestive system cancers in AYAs, both males and females showed a decreasing trend. For AYAs with CRC, the fastest increase in ASIR (AAPC: 0.73) was observed in the 30–34 age group. Regarding SDI regions, we found that the ASIR of AYAs with CRC increased in all five Social Demographic Index (SDI) regions. For AYAs with PC, the burden was increased in low and low-middle SDI. In the AYAs with LC, the ASIR also increased in low-middle SDI. For AYAs with EC and GC, both showed a decreasing trend across all five SDI regions. Conclusion The study results provide insights into the global distribution and severity of the burden of digestive system cancers among AYAs. The burden of AYAs with CRC is rapidly increasing worldwide, particularly among males, those aged 30–34, and in high-middle SDI. The disease burden varies across different SDI regions. These findings highlight the need for targeted preventive measures and suggest adjusting CRC screening guidelines.

Correction: Implementation status of maternal death surveillance and response system in Ethiopia: Evidence from a national-level system evaluation

Cohort profile: Design and methods for Project HERCULES (Healthcare Exemplar for Recovery from COVID 19 Using Linear Examination Systems): Multi-disciplinary implementation and evaluation of an asynchronous review clinic in NHS eye-care services

Objectives To describe the research principles and cohort characteristics of the multi-disciplinary Project HERCULES, an innovative model of safe high-volume outpatient eye-care service for patients with stable chronic eye diseases. Results and analyses of the workstreams within Project HERCULES will be reported elsewhere. The rationale was to improve eye-care capacity in the National Health Service (NHS) in England through the creation of technician-delivered monitoring in a large retail-unit in a London shopping-centre, with remote asynchronous review of results by clinicians (named Eye-Testing and Review through Asynchronous Clinic (Eye-TRAC)). UCL’s Bartlett School of Sustainable Construction developed the RIBA (Royal Institute of British Architects) Stage 1 briefing requirements for optimal design specifications for this model of care from first principles research, by analysing ergonomic data from multiple iterations. Methods Patients aged 18 years or above being monitored in secondary care in Moorfields Eye Hospital NHS Trust for stable glaucoma or retinal conditions were given appointments at Eye-TRAC at Brent Cross, London. Patients were also recruited at City Road and Hoxton Eye-TRACs, as comparators for the motion tracking study. Willing participants were recruited when attending Eye-TRAC from 11th October 2021–1st December 2023, during this time four spatial “iterations,” with different configurations of equipment were investigated in succession. Recruited participants provided information on their eye health and quality of life via a questionnaire, as well as agreeing to wear a tracking device. The tracking device was worn for the duration of their clinic visit and along with directly observed timings built a picture of patient and staff flow through the clinic. Rapid qualitative and ethnographic analyses were conducted, drawing on staff, manager and patient interviews and observation of service delivery and challenges. Separately, anonymised data from across the Trust informed an analysis of the impact of opening the Eye-TRACs on Trust-wide waiting times. A nationwide discrete choice experiment was also conducted to assess patients’, healthcare providers’, and the public’s preferences for key service features.. Findings to date and conclusion 41,567 patients attended the Brent Cross Eye-TRAC between 11th October 2021 and 1st December 2023. 5,539 patients were recruited to Project HERCULES. Spatial configurations promoting independently parallel patient journeys with limited queuing, and direct line of sight between diagnostic stations, supported efficient patient flow. The latter iteration incorporated cataract clinics. Although it added more system complexity, it enabled the evaluation of a further indication for use of Eye-TRAC. Future plans The analysis of trust-wide data on the impact of the Eye-TRACs on waiting times and a nationwide evaluation of stakeholders’ preferences regarding diagnostic and monitoring services for stable disease are underway. We will also identify and enumerate limitations in information technology that create bottlenecks in the review process. Qualitative analysis of patient and staff feedback alongside rapid ethnographic work to streamline services is also under way. We seek to develop a framework to help inform NHS guidance and future service planning for ophthalmology and other outpatient diagnostic services. Our data will be analysed to identify enhancements to further streamline operational efficiency.

Correction: An update on health literacy dimensions: An umbrella review

Science of music-based citizen science: How seeing influences hearing

Citizen science engages volunteers to contribute data to scientific projects, often through visual annotation tasks. Hearing based activities are rare and less well understood. Having high quality annotations of performed music structures is essential for reliable algorithmic analysis of recorded music with applications ranging from music information retrieval to music therapy. Music annotations typically begin with an aural input combined with a variety of visual representations, but the impact of the visuals and aural inputs on the annotations are not known. Here, we present a study where participants annotate music segmentation boundaries of variable strengths given only visuals (audio waveform or piano roll) or only audio or both visuals and audio simultaneously. Participants were presented with the set of 33 contrasting theme and variations extracted from a through-recorded performance of Beethoven’s 32 Variations in C minor, WoO 80, under differing audiovisual conditions. Their segmentation boundaries were visualized using boundary credence profiles and compared using the unbalanced optimal transport distance, which tracks boundary weights and penalizes boundary removal, and compared to the F-measure. Compared to annotations derived from audio/visual (cross-modal) input (considered as the gold standard for our study), boundary annotations derived from visual (unimodal) input were closer than those derived from audio (unimodal) input. The presence of visuals led to larger peaks in boundary credence profiles, marking clearer global segmentations, while audio helped resolve discrepancies and capture subtle segmentation cues. We conclude that audio and visual inputs can be used as cognitive scaffolding to enhance results in large-scale citizen science annotation of music media and to support data analysis and interpretation. In summary, visuals provide cues for big structures, but complex structural nuances are better discerned by ear.

Peptidylarginine deiminase 4 deficiency alleviates hypoxia/reoxygenation-induced cardiomyocyte injury

Background Cardiac ischemia reperfusion (I/R) injury is a serious consequence of reperfusion therapy for myocardial infarction (MI). Peptidylarginine deiminase 4 (PAD4) is a calcium-dependent enzyme that catalyzes the citrullination of proteins. In previous studies, PAD4 inhibition protected distinct organs from I/R injury by preventing the formation of neutrophil extracellular traps (NETs) and attenuating inflammatory responses. Here, we hypothesized that cardiomyocyte PAD4 expression may play a role in acute I/R injury. Methods Infarct size was determined in isolated pressure constant-perfused hearts from WT and PAD4-deficient (PAD4-/-) mice. Additionally, extracellular reactive oxygen species (ROS) and cell viability were quantified in freshly isolated adult cardiomyocytes exposed to hypoxia followed by reoxygenation (H/R). Resistance to oxidative stress was proven in both genotypes by treatment of neonatal cardiomyocytes with hydrogen peroxide. Moreover, intracellular ROS formation, ATP production, mitochondrial membrane polarisation, caspase-3 activation, and cell viability were quantified after hypoxia followed by 4 h and 20 h of reoxygenation, respectively. The PAD4-specific inhibitor GSK484 was added before H/R or at reperfusion in certain experiments. Results Infarct size was smaller in PAD4-/- hearts following I/R when compared to the WT. Similarly, the viability of adult and neonatal PAD4-/- cardiomyocytes was better preserved after H/R, accompanied by reduced ROS formation. PAD4 deficiency maintained mitochondrial integrity and protected neonatal cardiomyocytes against apoptosis. However, these cells did not exhibit resistance to hydrogen peroxide-induced cell death, indicating an unaltered antioxidative state. Whereas pharmacological PAD4 inhibition by GSK484 before H/R sustained intracellular ATP levels in WT cardiomyocytes, administration of GSK484 at reoxygenation did not. However, GSK484 significantly improved cardiomyocyte metabolic activity, regardless of the time of administration. Conclusions Our study is the first to demonstrate that PAD4 expression in cardiomyocytes contributes to H/R injury independent of systemic immune responses and NETs. Consequently, PAD4 may serve as a therapeutic target to alleviate I/R injury.

Freestyle master’s swimming: Nationality, sex, and performance trends in World Aquatics competitions (1986–2024)

Background In sports science, freestyle swimming has been thoroughly studied for particular performance-related factors. Nonetheless, it is unknown what countries the top freestyle swimmers are from, especially not for age group swimmers. In addition, the existing research on the performance of master freestyle swimmers has yet to confirm that male swimmers achieve faster times than their female counterparts across all age groups and distances. The current study looked into the nationalities and sexes of the top freestyle swimmers in each age group in World Aquatics competitions for the 50m, 100m, 200m, 400m, and 800m events from 1986 to 2024. Methods The data (derived from (www.worldaquatics.com/masters/archives/masters-archives) were presented using mean, standard deviation, maximum and minimum values, and/or confidence intervals. The year of competition, age, age group, stroke, distance, and first and last names of each swimmer were noted. The nations were then divided into six groups: one group comprising all other countries and the top five nations with the greatest number of appearances in the top 10 fastest freestyle swimming times by distance each year. Results In freestyle swimming, most swimmers (30.6%) competed in the 50m event (n = 25,094, 10,909 female and 14,185 male), followed by the 100m event (25.6%, n = 20,961, 8,796 female and 12,165 male), the 200m event (17.4%, n = 14,309, 6,729 female and 7,580 male), the 400m event (13.4%, n = 10,956, 5,363 female and 5,593 male), and the 800m event (12.6%, n = 10,317, 5,179 female and 5,138 male). The results from the generalized linear models indicate that sex, age group, and the interaction between sex and age group all had significant effects on the 50m, 100m, 200m, 400m, and 800m races. Specifically, for the 50m races, the effect of sex was significant (x2 (1) = 3451.941, p < 0.001), as was the effect of age group (χ2 (13) = 19,295.169, p < 0.001), and the interaction between sex and age group (χ 2 (13) = 654.671, p < 0.001). Conclusion The USA demonstrates quantitative dominance by contributing the greatest number of top 10 performers. Additionally, the study highlights significant sex-based performance differences, with males generally outperforming females in all age categories. This study comprehensively analyzes the performance trends observed in freestyle master swimming for nearly four decades.

Determinants of access to insecticide-treated nets in Sub-Saharan Africa: A multilevel cross-country analysis using 29 DHS data

Background Having access to Insecticide-Treated Nets (ITNs) is crucial for avoiding malaria in Sub-Saharan Africa (SSA), where the disease burden is disproportionately high. Despite their efficacy, socioeconomic, demographic, and geographic factors continue to cause notable differences in ITN access within and between nations. By employing a multilevel analysis of data from 29 Demographic and Health Surveys (DHS) throughout SSA, this study seeks to fill knowledge gaps about the factors that influence access at the individual and community levels. Methods The study utilized data from 29 DHS surveys in SSA, which encompassed 214,181 households. Factors affecting access to ITN at the individual and community levels were examined using multilevel logistic regression models. Household head characteristics (sex, marital status, education, wealth index, television access, and family size) were among the individual-level factors. On the other hand, community-level characteristics included geography, kind of home, poverty, media exposure, and education. The Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and deviance were used to evaluate the model’s fitness. Measures of variation, including the Median Odds Ratio (MOR), Proportional Change in Variance (PCV), and Intraclass Correlation Coefficient (ICC), were used to assess the effects at the community level. Results ITNs were reported by just 32.11% of households, with notable differences across socioeconomic classes and geographical areas. Higher ITN access was substantially correlated with married household heads, wealthier families, larger family sizes, and higher educational attainment. Access was also greatly enhanced by community-level factors such as urban residency, media exposure, and higher education. The best fit was Model 3, which explained 15.24% of the variance in ITN access by combining characteristics at the person and community levels. There were clear regional differences, with West Africa having higher probabilities of access than East Africa (AOR = 4.48). Conclusion The study highlights the multifaceted determinants of ITN access in SSA, emphasizing the need for targeted interventions addressing both individual and community-level barriers. Strengthening distribution networks, increasing funding for subsidized ITN programs and enhancing public health education is essential for achieving universal coverage and reducing the malaria burden in the region.

An improved nuclei isolation protocol from leaf tissue for single-cell transcriptomics

The study of plant biology has traditionally focused on investigations conducted at the tissue, organ, or whole plant level. However, single-cell transcriptomics has recently emerged as an important tool for plant biology, enabling researchers to uncover the expression profiles of individual cell types within a tissue. The application of this tool has revealed new insights into cell-to-cell gene expression heterogeneity and has opened new avenues for research in plant biology. A critical step in the successful application of single-cell and single-nuclei RNA-seq (scRNA-seq and snRNA-seq) is the isolation of individual cells or nuclei, respectively, from tissue to recover their transcriptional profile. A critical step during nuclei isolation for snRNA-seq studies is Fluorescent-Activated Cell Sorting (FACS). During this step, nuclei stained with DAPI (4′,6-diamidino-2-phenylindole) can be sorted and separated from cell debris and organelles. Leaf tissue presents a unique challenge due to its high content of chloroplasts, which can interfere with obtaining high-quality results. Because DAPI can also bind to the plastid genome, these organelles will be sorted as nuclei. Thus, in tissues with a high content of chloroplasts, we have a high contamination of these organelles and an overestimation of the number of nuclei. In this study, we introduce a straightforward alternative method for isolating nuclei from Zea mays leaves with reduced chloroplast contamination. By effectively removing chloroplasts during the FACS step of our protocol, using the autofluorescence from the chloroplasts, we achieved improved alignment of reads to the genome and transcriptome. Our enhanced protocol offers a valuable solution for applying snRNA-seq in tissues with a high content of chloroplasts.

Multi-scale diffusion model for underwater image restoration and enhancement

Background: Underwater environments face challenges with image degradation due to light absorption and scattering, resulting in blurring, reduced contrast, and color distortion. This significantly impacts underwater exploration and environmental monitoring, necessitating advanced algorithms for effective enhancement. Objectives: The study aims to develop an innovative underwater image enhancement algorithm that integrates physical models with deep learning to improve visual quality and surpass existing methods in performance metrics. Methods: The proposed method employs a multi-level design combining physical insights from the diffusion model with deep learning. It utilizes an encoder-decoder pipeline for image decomposition, adaptive color adjustment through a color encoder network, and pixel optimization using an inverse denoising diffusion model to achieve enhanced visual quality. Results and conclusion: Experimental results demonstrate significant improvements, with an average increase of 6.61 in PSNR, 0.15 in SSIM, and 0.87 in UIQM. The integration of physical models and deep learning proves effective for underwater image enhancement. This research advances the field by providing a robust framework for addressing imaging challenges in underwater environments.

Editorial Note: Agricultural total factor productivity, digital economy and agricultural high-quality development

Evidence for coopetition at the maternal–fetal interface shaping placental invasion

Coopetition is a term from game theory that describes a mix of cooperative and competitive behavior. The maternal–fetal interface (MFI) among eutherian mammals presents close interaction of two distinct individuals. These interactions have resulted in a remarkable diversity in MFI structure, often interpreted as the outcome of maternal–fetal conflict. Nevertheless, the fetus and the mother share evolutionary interests since 50% of fetal genes are maternal. In hemochorial species, characterized by invasive placentation, endometrial stromal fibroblasts (ESFs) undergo decidualization to regulate embryo implantation. In great apes, hemochorial placentation is driven by highly invasive extravillous trophoblast cells (EVT). Here, using EVTs differentiated from trophoblast stem cells, term placenta, as well as HTR8/SVneo, we demonstrate that EVTs orchestrate a transformation of the maternal stroma, reducing its resistance to invasion acquired during decidualization. Through paracrine signals, in particular IL-11, trophoblasts transform decidual ESFs from a matrix-producing to a matrix-degrading state. Notably, noninvasive cytotrophoblast cells, do not transform decidual ESFs. We further provide evidence that maternal coadaptation is critical to EVT-induced decidual transformation. Decidual ESFs upregulate expression of Suppressor of Cytokine Signaling 3 in response to EVTs, rewiring downstream IL-11 signaling from JAK/STAT to AP-1 specific transcription. We conclude that the evolution of highly invasive placentation is the outcome of both the evolution of invasive EVTs, as well as the evolution of maternal traits, i.e., the switch from JAK/STAT to AP-1 signaling. We interpret this as evidence for co-opetition (cooperation among competitors).

A thermodynamic perspective on mammalian neural crest ingression

The ingression of neural crest cells from an ectodermal to a mesodermal layer is regulated by instructive, directional cues and potentially stochastic, biophysical parameters such as differential cell adhesion and tension heterogeneity. However, a cohesive framework in which to consider how various influences contribute to ingression remains elusive. Here, we observe the cell behaviors of the murine neural crest in three dimensions over time and apply a free energy framework to more wholly understand why cells ingress. Guided by work on granular matter that provides a path by which to define the roles of stochastic mechanisms in nonequilibrium systems, we measured and manipulated biophysical parameters in vivo. The data suggest that an energy barrier to cell ingression is overcome by a combination of relatively favorable cell adhesion energies, high cell shape fluctuations, and entropic cell packing configurations. Under those conditions, cell ingression may proceed spontaneously. Recognized biophysical cues likely tilt these parameters to make the process more robust. The results imply that dissipative mechanisms which transiently disorder tissue may underlie some morphogenetic events. Variations of a thermodynamic framework can potentially be applied to integrate various inputs that drive morphogenesis in different contexts.

Complementary biomolecular coassemblies direct energy transport for cardiac photostimulators

Charge and energy transport within living systems are fundamental processes that enable the autonomous function of excitable cells and tissues. To date, localized control of these transport processes has been enabled by genetic modification approaches to render light sensitivity to cells. Here, we present peptidic nanoassemblies as constituents of a cardiac biomaterial platform that leverages complementary sequence interactions to direct photoinduced energy transport at the cellular interface. Photophysical characterizations and conductivity measurements confirm the occurrence of energy/charge transfer and photocurrent generation upon optical excitation in both dry and electrolytic environments. Comparing an electrostatic sequence pair against a sequence-matched donor–acceptor coassembly, we demonstrate that the sequence design with charge complementarity shows more prominent photocurrent behavior. With the flanking bioadhesive units, the primary and stem cell–derived cardiomyocytes interfaced with covalently stabilized films of the optoelectronic nanostructures exhibited material-stimulated genotypic, structural, or functional cardiac features. Collectively, our findings introduce an optoelectronic cardiac biomaterial where coassembled peptide nanostructures are molecularly designed to induce light sensitivity in excitable cells without gene modification, influencing in vitro cardiac contractile behavior and expression of cardiac markers.

Topology and kinetic pathways of colloidosome assembly and disassembly

Closed capsules, such as lipid vesicles, soap bubbles, and emulsion droplets, are ubiquitous throughout biology, engineered matter, and everyday life. Their creation and disintegration are defined by a singularity that separates a topologically distinct extended liquid film from a boundary-free closed shell. Such topology-changing processes are of fundamental interest. They are also essential for intercellular transport, transcellular communication, and drug delivery. However, studies of vesicle formation are challenging because of the rapid dynamics and small length scale involved. We develop fluid colloidosomes, micrometer-sized analogues of lipid vesicles. The mechanics of colloidosomes and lipid vesicles are described by the same theoretical model. We study colloidosomes close to their disk-to-sphere topological transition. Intrinsic colloidal length and time scales slow down the dynamics to reveal colloidosome conformations in real time during their assembly and disassembly. Remarkably, the lowest-energy pathway by which a closed vesicle transforms into a flat disk involves a topologically distinct cylinder-like intermediate. These results reveal aspects of topological changes that are relevant to all liquid capsules. They also provide a robust platform for the encapsulation, transport, and delivery of nanosized cargoes.

A general genome editing strategy using CRISPR lipid nanoparticle spherical nucleic acids

Genome editing with CRISPR–Cas systems hold promise for treating a wide range of genetic disorders and cancers. However, efficient delivery of genome editors remains challenging due to the requirement for the simultaneous delivery or intracellular generation of Cas proteins, guide RNAs, and, in some applications, donor DNAs. Furthermore, the immunogenicity and toxicity of delivery vehicles can limit the safety and efficacy of genetic medicines. Here, we combine two nucleic acid delivery approaches to create CRISPR lipid nanoparticle–spherical nucleic acids (LNP–SNAs) that are both efficient and biocompatible. Compared to lipid nanoparticles (LNPs) lacking a surface-bound DNA shell, CRISPR LNP–SNAs exhibit two- to three-fold higher cellular uptake, reduced cytotoxicity, and improved gene transfection efficiency. Across multiple cell lines and genomic loci, CRISPR LNP–SNAs induce insertion–deletion mutations at average frequencies two- to three-fold higher than those observed with LNPs. When codelivered with donor templates, CRISPR LNP–SNAs enable homology-directed repair at an average efficiency of 21 ± 7%, a 2.5-fold improvement over LNPs (8 ± 4%). The ease of synthesis and biocompatibility of CRISPR LNP–SNAs highlight their potential as a versatile delivery platform for CRISPR–Cas and other gene therapies.

Preschool teachers provide fewer participation opportunities to working-class students than those from more privileged backgrounds

Social class disparities exist from the earliest stages of education. Research has suggested that class-based differences in factors such as socialization practices and access to resources partly explain this phenomenon, but less work has explored whether teachers’ practices also exacerbate these inequalities. Using whole-class observations of 63 preschool classroom discussions ( N = 226 students, 10 teachers), we coded 7,941 student participation attempts and subsequent responses from teachers. Mixed-effects Bayesian logistic regressions showed that whether students played by the rules by raising their hands or broke the rules by calling out, they were less likely to have their participation attempts accepted if they came from a working-class background, even when their perceived language skills were matched to their middle- and upper-class peers. These results suggest that early schooling experiences may serve to exacerbate inequalities rather than level the playing field.