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Intravitreal injection of cell membrane-coated nanoparticles for retinoblastoma treatment
Get PDFChemotherapy is a widely adopted treatment for malignant intraocular tumors such as retinoblastoma. However, achieving high delivery efficiency remains challenging due to rapid clearance and lack of targeting specificity. Cancer cell membrane-coated nanoparticles have been extensively reported to exhibit specific affinity to homotypic cancer cells. Here we designed poly (lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles coated with the plasma membrane of WERI-Rb-1 cells, derived from human retinoblastoma. These nanoparticles showed remarkable affinity to WERI-Rb-1 cells in vitro. Loaded with the FDA-approved chemotherapy drug etoposide, the nanoparticles exhibited excellent antitumor efficacy and excellent biosafety following a single-dose intravitreal injection in vivo. Overall, this work presents a simple yet effective strategy for the treatment of retinoblastoma.published_or_final_versio
Self-administered dual-task training reduces balance deficits and falls among community-dwelling older adults: A multicentre parallel-group randomised controlled trial with economic evaluation protocol
Get PDFBackground Falls are common causes of disability, reduced disability-adjusted life years and death in older adults. Balance deficits and cognitive impairment are common causes of falls. Dual-task training is a new strategy that can potentially improve balance and cognitive function, leading to decreased falls. The effectiveness and cost-effectiveness of self-administered dual-task (sDT) training to improve balance and prevent falls is not known. We developed sDT training combining physical and cognitive tasks to improve balance and reduce falls. The proposed randomised controlled trial (RCT) with economic evaluation is to test the effectiveness and cost-effectiveness of the sDT compared with self-administered single-task training (sST) in this population. Methods and analysis In this RCT, we will recruit 190 community-dwelling older adults with a history of at least one fall over the last 6 months from 11 elderly centres. The older adults will be randomly assigned to the sDT (n=95) and sST groups (n=95). Each group will be offered in six training workshops to teach the participants either sDT or sST depending on the group allocation. Each workshop will last an hour and will be held once every 2 weeks for 3 months. Besides, the participants will be instructed to repeat the exercises at home two times weekly for 3 months. Following the intervention phase, the participants will continue unsupervised home-based exercises for 6 months. Assessments will be performed before, after and 6 months after completing the intervention. A fall calendar and cost diary will be provided to each older adult to record the number of falls and fall-related costs during and after the intervention to assess fall incidence and cost-effectiveness. Effectiveness will be assessed using a negative binomial regression model following the intention-to-treat principle for falls and a linear mixed model for the additional measure and cost-effectiveness using a Markov model. Ethics and dissemination This study has ethical approval from the PolyU Institutional Review Board for conducting research on human subjects (Ref: HSEARS20210322005). The results will be disseminated through seminars for individuals and health practitioners, international conferences and published in peer-reviewed journals.published_or_final_versio
Neural correlates of religious behavior related to Christianity: an ALE meta-analysis
No full textBackground: Multiple neuroimaging studies have been published to report brain processing of religious behavior related to Christianity, such as prayer and recitation of the Bible. This meta-analysis aimed to pool data across studies to identify brain regions consistently activated in response to such religious tasks. Methods: Web of Science, Scopus, and PubMed were queried to identify relevant studies. Brain coordinates and sample size were manually extracted from the identified studies, and entered into a dedicated software called GingerALE to conduct meta-analysis. Results: Meta-analytic results based on 11 studies showed that brain processing of Christian behavior was associated with the right middle frontal gyrus and superior frontal gyrus, with a peak location (at 44, 38, 26; cluster size = 760 mm3) preferentially associated with working memory, cognitive task, and executive function according to Neurosynth data. Sub-analyses on Christian subject data revealed no significant results at the pre-defined threshold. With a more liberal threshold, Christian tasks > non-Christian tasks showed activation in the anterior cingulate and medial frontal gyrus (peak at 4, 48, −4; cluster size = 256 mm3) that were frequently associated with reward, self-referential, and reinforcement learning, whereas non-Christian tasks > Christian tasks showed activation in the right middle frontal gyrus (peak at 48, 36, 24; cluster size = 472 mm3) that frequently associated with working memory, executive function, arithmetic, and calculation. Conclusion: This study has revealed the relevance of frontal and limbic regions to Christian behavior.</p
Genetic influence and neural pathways underlying the dose-response relationships between wearable-measured physical activity and mental health in adolescence
No full textAdolescence is a critical period marked by significant physical and neurocognitive development as well as increased vulnerability to mental health issues. While the benefits of physical activity (PA) on adult mental health (MH) are well-established, the dose-response relationships and underlying neurobiological mechanisms in adolescents remain elusive. This study investigated the dose-response relationships between wearable-measured PA and MH outcomes in over 7000 adolescents (11–12 years) from the ABCD study through linear and nonlinear modeling. We further examined the genetic influence and mediation effects of brain structure and function underlying the relationships. We found that all intensity levels of PA were associated with reduced internalizing and thought problems but not with externalizing problems. Durations of moderate activity around 90 min and vigorous activity around 120 min each day and frequency of physical exercise four days each week were associated with lowest MH burden. Polygenic risk scores (PRSs) for neuropsychiatric disorders were associated with reduced step count and light activity, while PRS for walking was associated with reduced thought problems. Reduced functional connectivity between cingulo-parietal and auditory networks, and between cingulo-opercular network and left putamen is the common neural pathways mediating the associations between different PA measurements and better mental health. These findings suggest that excessive moderate and vigorous activity may not be always better for adolescent mental health. Brain functional integration and segregation centered on cognitive control as well as genetic interplay may be the potential neurobiological factors underlying the link between PA and MH
Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD
Get PDFObjectiveAttention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a significant genetic component. The latest genome-wide association study (GWAS) meta-analysis of ADHD identified 27 whole-genome significant risk loci in the European population. However, genetic risk factors for ADHD are less well-characterized in the Asian population, especially for low-frequency / rare variants.MethodsIn this study, we aimed to investigate the contributions of both common and low-frequency / rare variants to ADHD in a Hong Kong sample. Our sample comprised 279 cases and 432 controls who underwent genotyping using the Illumina Infinium Global Screening Array. We employed various analytical methods at different levels, while also leveraging multi-omics data and large-scale summary statistics to comprehensively analyze the genetic basis of ADHD.ResultsWe identified 41 potential genomic risk loci with a suggestive association (p −4), pointing to 111 candidate risk genes, which were enriched for genes differentially expressed during late infancy brain development. Furthermore, tissue enrichment analysis implicated the involvement of the cerebellum. At the polygenic level, we also discovered a strong genetic correlation with resting-state functional MRI connectivity of the cerebellum involved in the attention/central executive and subcortical-cerebellum networks. In addition, an accumulation of ADHD common-variant risks found in European ancestry samples was found to be significantly associated with ADHD in the current study. In low-frequency / rare variant analyses, we discovered the correlations between ADHD and collapsing effects of rare damaging variants in TEP1, MTMR10, DBH, TBCC, and ANO1. Based on biological and functional profiles of the potential risk genes and gene sets, both common and low-frequency / rare variant analyses demonstrated that ADHD genetic risk was associated with immune processes.ConclusionsThese findings re-validate the abnormal development of the neural system in ADHD and extend the existing neuro-dysfunction hypothesis to a multi-system perspective. The current study identified convergent risk factors from common and low-frequency / rare variants, which implicates vulnerability in late-infancy brain development, affecting especially the cerebellum, and the involvement of immune processes.published_or_final_versio
Monthly methane emissions in Chinese mainland provinces from 2013–2022
No full textAs the world’s largest source of methane emissions, accurately measuring and tracking China’s emissions across various sectors is essential for global climate change efforts. Methane, a potent greenhouse gas, is emitted from diverse anthropogenic and natural sources, many of which exhibit pronounced temporal variability. In particular, emissions from rice cultivation, energy use, and livestock management show strong seasonal patterns, yet high-frequency and spatially detailed methane emission inventories have been lacking. This study introduces the Monthly Methane Emission Inventory for China’s Provinces (MMCP), a comprehensive dataset covering the period from January 2013 to December 2022. The dataset includes emissions data from eight key sectors: coal mining, oil and gas systems, energy combustion, rice cultivation, livestock, solid waste, wastewater, and wetlands. By offering sector-specific and temporally resolved emission estimates, MMCP serves as a valuable resource for scientific research, policy evaluation, and emission mitigation planning. This inventory facilitates improved understanding of emission trends and supports more accurate modeling of atmospheric methane concentrations and climate feedbacks.</p
A prospective comparison of sequential versus interval retreatment with radiofrequency ablation for predominantly solid, large-volume benign thyroid nodules
No full textRadiofrequency ablation (RFA) is an effective treatment for benign thyroid nodules. For large nodules ≥20ml, retreatment within 6 month would lead to higher volume reduction rate (VRR) at 12-month than single treatment. However, the optimal timing of retreatment within the 6-month period has not been determined. This prospective study compared sequential versus interval retreatment with RFA for predominantly solid, large benign thyroid nodules ≥20ml, and identified factors associated with better VRR.</p
Social skills and audience agency in improvised social performance
No full textPerformance theories treat social action as relatively improvisational, but how such spontaneous and unscripted actions manage to succeed with audiences is undertheorized. Cultural pragmatics is exceptional in this regard, specifying the elements of successful performances and placing particular emphasis on the dramatic skills of actors and the agency of audiences. But how exactly do actors make use of the active character of audiences in achieving performative success? In this article, I draw from interview and observational data on improvisational theatre to analyse and catalogue the skills and techniques that improvisers employ to engage their audiences. I find that improvisers achieve performative success consistently by exercising varying degree of “restrained reciprocity” with audiences, and developing skills and techniques to generate enthusiastic responses, make inferences about the audiences mental and emotional states, tailor performances to audience preferences, and coordinate performances with the affordances of performance venues. I use these insights to refine the conceptualization of dramatic skills, fusion, and mise-en-scène within cultural pragmatics.</p
Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex
Get PDFHow the ubiquitously expressed splicing factors specifically regulate neural crest (NC) development and enhance their vulnerability to splicing perturbations remain poorly understood. Here, we show that NC-specific DLC1, partnering with SF3B1-PHF5A splicing complex, are crucial for determining avian trunk NC cell fate by regulating the splicing of NC specifiers SOX9 and SNAI2 pre-mRNAs rather than their upstream regulators BMP4, WNT1, and PAX7. Mechanistically, SF3B1-PHF5A binds to the intronic branch site (BS) sequences of all factors, while DLC1 interacts with a specific motif near the BS sequences of SOX9 and SNAI2, thereby determining their functional specificity in NC specification. Moreover, DLC1 increases NC cells’ vulnerability to splicing modulator pladienolide B (PB) by reducing the binding capacity of the SF3B1-PHF5A splicing complex to the shorter length of both SOX9intron 2 and SNAI2 intron 1, which possess weaker polypyrimidine tract 3’ of the BS sequence, resulting in intron retention and loss of NC progenitors. Conversely, somite specific SLU7-SF3B1-PHF5A splicing complex regulates SOX9 and SNAI2 expression and imparts resistance to PB. Our data reveal the cell-type specific splicing complexes with distinct vulnerabilities to PB, highlighting the critical role of the DLC1-SF3B1-PHF5A in determining trunk NC cell fate and enhancing its susceptibility to splicing perturbation.published_or_final_versio