Health Biomed (China)

Immunotherapy has emerged as a pivotal strategy for restoring immune balance in diseased tissues, harnessing the immune system to eliminate malignant cells and suppress aberrant inflammatory responses at lesional sites while sparing healthy adjacent tissues. Programmable nucleic acid origami nanostructures can be precisely modified with diverse biomolecules at designated sites, making them superior delivery carriers for immune modulation. This review highlights the transformative therapeutic potential of nucleic acid origami nanostructures in the immunotherapy of cancer, inflammatory, and autoimmune diseases through regulation of both innate and adaptive immune pathways. Particular attention is given to their applications in antigen/adjuvant co-delivery for vaccine design, cytokine delivery, adoptive cell therapies, and combination immunotherapies. We further summarize current biomedical applications and clinical translation efforts, critically evaluating both opportunities and limitations. Overall, this review underscores the promise of nucleic acid origami nanostructures to redefine personalized immunotherapy and provides perspectives for future research directions. • Precision Immunomodulation: Nucleic acid origami nanostructures offer unparalleled spatial control for the precise delivery and presentation of immunotherapeutic agents, enabling targeted immune activation or suppression while sparing healthy tissues. • Multifunctional Therapeutic Platforms: Nucleic acid origami nanostructures function not merely as passive carriers but as active scaffolds that can directly engage and modulate innate and adaptive immune pathways. • Broad Application Potential: The nucleic acid origami technology holds transformative promise for treating a wide range of conditions, including cancer, inflammatory, and autoimmune diseases, through applications in vaccine design, adoptive cell therapy, and chemo-combination immunotherapies.

High-protein foods and physical activity are crucial for bone growth in early life. This study first examined whether a protein-rich multi-nutrient intervention combined with rope-skipping training could prevent bone loss during winter in prepubertal children. A 10 week randomized controlled trial involving 120 children aged 9-12 years in rural northwestern China was conducted. Participants were assigned to a treatment group (protein-rich multi-nutritional drink plus rope-skipping training) or a control group (rope-skipping training only). Forearm bone mineral density (BMD) was measured at the baseline and week 10 of the trial, along with serum calcium, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), and bone turnover biomarkers. Second, we estimated the effects of three protein sources enriched in the drink, milk protein concentrates (MPC), collagen peptides (CP), and whey protein hydrolysates (WPH), on zebrafish backbone development. In children, BMD decreased in both groups, but the treatment group showed a smaller reduction and a positive intervention effect (relative change: 0.023 g cm-2, P = 0.037). The treatment group also had a smaller increase in PTH (relative change: -8.53 ng L-1, P = 0.012) and a smaller decrease in IGF-1 (relative change: 20.75 ng mL-1, P = 0.076). No significant differences were found in bone turnover biomarkers. In zebrafish, MPC, CP, and WPH individually and synergistically promoted bone growth without adverse effects, as shown by dose-dependent increases in the backbone fluorescence intensity. These findings suggest that protein-rich multi-nutrient supplementation combined with rope-skipping training could prevent bone loss in prepubertal children during winter, potentially through changes in serum PTH and IGF-1, and highlight the synergistic effects of these proteins on bone development.

BackgroundChildhood bullying is a public health priority. We evaluated the effectiveness and costs of KiVa, a whole-school anti-bullying program that targets the peer context.MethodsA two-arm pragmatic multicenter cluster randomized controlled trial with embedded economic evaluation. Schools were randomized to KiVa-intervention or usual practice (UP), stratified on school size and Free School Meals eligibility. KiVa was delivered by trained teachers across one school year. Follow-up was at 12 months post randomization. Primary outcome: student-reported bullying-victimization; secondary outcomes: self-reported bullying-perpetration, participant roles in bullying, empathy and teacher-reported Strengths and Difficulties Questionnaire. Outcomes were analyzed using multilevel linear and logistic regression models.FindingsBetween 8/11/2019–12/02/2021, 118 primary schools were recruited in four trial sites, 11 111 students in primary analysis (KiVa-intervention: n = 5944; 49.6% female; UP: n = 5167, 49.0% female). At baseline, 21.6% of students reported being bullied in the UP group and 20.3% in the KiVa-intervention group, reducing to 20.7% in the UP group and 17.7% in the KiVa-intervention group at follow-up (odds ratio 0.87; 95% confidence interval 0.78 to 0.97, p value = 0.009). Students in the KiVa group had significantly higher empathy and reduced peer problems. We found no differences in bullying perpetration, school wellbeing, emotional or behavioral problems. A priori subgroup analyses revealed no differences in effectiveness by socioeconomic gradient, or by gender. KiVa costs £20.78 more per pupil than usual practice in the first year, and £1.65 more per pupil in subsequent years.InterpretationThe KiVa anti-bullying program is effective at reducing bullying victimization with small-moderate effects of public health importance.FundingThe study was funded by the UK National Institute for Health and Care Research (NIHR) Public Health Research program (17-92-11). Intervention costs were funded by the Rayne Foundation, GwE North Wales Regional School Improvement Service, Children's Services, Devon County Council and HSBC Global Services (UK) Ltd.

Edvard Munch, a founder of Expressionism was pre-occupied with depicting his subjective experience and the most prolific painter of self-portraits since Rembrandt. Based on evidence that faces and self-related images are more salient than other objects it is plausible that self-portraits, in which the subject and object are the same, reflect the artist’s state of mind. Although he suffered from a variety of physical and psychological illness Munch was not diagnosed with any specificity in his lifetime. Posthumous diagnoses include schizophrenia, anxiety, bipolar and other disorders. Recent research has revealed altered visual perception in such patients. The present study empirically analysed three stylistic elements of Munch’s painted self-portraits and portraits: contrast, colour and fractal dimension and his painted productivity, to determine if variations correlate with critical life events and if so whether they indicate states of mind. It found significant increases in contrast and colour brightness and persistent high complexity during critical periods supporting the conclusion that Munch is diagnostically best described as suffering from early onset schizophrenia and comorbid social anxiety disorder.

Studies typically highlight area level variation in the incidence of non-affective but not affective psychoses. We compared neighbourhood-level variation for both types of disorder, and the specific effects of neighbourhood urbanicity and ethnic density, using Danish national registry data. Population based cohort (2,224,464 people) followed from 1980 to 2013 with neighbourhood exposure measured at age 15 and incidence modelled using multilevel Poisson regression. Neighbourhood variation was similar for both disorders with an adjusted median risk ratio of 1.37 (95% CI 1.34-1.39) for non-affective psychosis and 1.43 (1.38-1.49) for affective psychosis. Associations with neighbourhood urbanicity differed: living in the most compared to the least urban quintile at age 15 was associated with a minimal increase in subsequent affective psychosis, IRR 1.13 (1.01-1.27) but a substantial increase in rates of non-affective psychosis, IRR 1.66 (1.57-1.75). Mixed results were found for neighbourhood ethnic density: for Middle Eastern migrants there was an increased average incidence of both affective, IRR 1.54 (1.19-1.99), and non-affective psychoses, 1.13 (1.04-1.23) associated with each decrease in ethnic density quintile, with a similar pattern for African migrants, but for European migrants ethnic density appeared to be associated with non-affective psychosis only. While overall variation and the effect of neighbourhood ethnic density were similar for both types of disorder, associations with urbanicity were largely confined to non-affective psychosis. This may reflect differences in aetiological pathways although the mechanism behind these differences remains unknown.

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X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the limited literature on eo-HM caused by ARR3 mutations shows that its inheritance mode is complex, which brings certain difficulties to pre-pregnancy genetic counseling, pre-implantation genetic diagnosis, and prenatal diagnosis. Here, we investigated the genetic underpinning of a Chinese family with eo-HM. Whole exome sequencing of the proband revealed a novel frameshift mutation in ARR3 (NM_004312, exon10, c.666delC, p. Asn222LysfsTer22). Although the mode of inheritance of the eo-HM family fits the X-linked pattern of ARR3, the phenotypes of three patients deviate from the typical early-onset high myopia. Through X-chromosome inactivation experiments, the patient's different phenotypes can be precisely explained. In addition, this study not only enhanced the correlation between ARR3 and early-onset high myopia but also provided explanations for different phenotypes, which may inspire follow-up studies. Our results enrich the knowledge of the variant spectrum in ARR3 and provide critical information for preimplantation and prenatal genetic testing, diagnosis, and counseling.