Impact of time period and birth cohort on the trend of advanced neoplasm prevalence in the 40-49 average-risk screening population.

BACKGROUND AND AIMS: Early-onset colorectal cancer (CRC) is increasing globally. While the United States have lowered the age of initiation of screening to 45, other countries still start screening at age 50. In Taiwan, the incidence of CRC has declined in 55-74 year-olds after the initiation of screening, but still increased in those 50-54, potentially due to rising precancerous lesion incidence in 40-49 year-olds. This study aimed to explore the chronological trend of the prevalence of colorectal advanced neoplasms (AN) in the screening population aged 40-54. METHODS: We retrospectively analyzed a screening colonoscopy cohort for prevalence of AN in average-risk subjects aged 40-54 from 2003 to 2019. Logistic regression was used to distinguish cohort effect from time-period effect on the prevalence of AN. RESULTS: In total, 27,805 subjects (52.1% male) men were enrolled. There were notable increases in prevalence of AN in all three age groups during the 17-year span, but these were more rapid in age 40-44 (0.99% to 3.22%) and 45-49 (2.50% to 4.19%). Age 50-54 had higher risk of AN [aOR=1.62(1.19-2.19)] in 2003-2008 but not in later periods [2009-2014: aOR=1.08(0.83-1.41)] and [2015-2019: aOR=0.76(0.56-1.03)] when compared with age 45-49. CONCLUSION: The prevalence of AN in age 40-54 increased in the Taiwanese population, with a later birth cohort having a higher prevalence of AN. However, the prevalence of AN in age 45-49 increased more remarkably and approximated that in age 50-54, which may justify earlier initiation of CRC screening at age 45.

Performance of red blood cell indices for the detection of reticulocytosis in anemic and non-anemic dogs in Taiwan.

Reticulocyte counts (RETIC) are considered the gold standard in detecting an erythroid bone marrow response (BMR) in anemic and non-anemic dogs. Reticulocytosis without anemia (RWA) is a potential indicator of disease. The prevalence of anemia or RWA, as well as the effectiveness of red blood cell (RBC) indices in identifying a BMR, may vary based on geographical locations and breed differences. The purpose of the study was to determine the prevalence of regenerative and nonregenerative anemia, and RWA in pet dogs of Taiwan, and to assess the sensitivity and specificity of combined increased mean cell volume and decreased mean cell hemoglobin concentration (iMCV+dMCHC) to detect reticulocytosis in this population. The final population analysis consisted of 149,076 dogs. A cross sectional, retrospective analysis of complete blood count (CBC) samples from a field of automated hematology analyzers in Taiwan from December 1, 2018 through December 31, 2020 was performed. Among 149,076 dogs, 11.8 % (n=17,600) had reticulocytosis (RETIC > 110K/µl) and 21.8 % (n=32,474) had anemia (HCT < 37.3 %). Of 32,474 anemic dogs, 17.8 % (n=5,789) had reticulocytosis. Of 116,602 dogs without anemia, 10.1 % (n=11,776) had reticulocytosis. Across all dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 4.3 % and 99.4 %, respectively compared to RETIC. Among anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 9.8 % and 99.2 %, respectively. Among non-anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 1.6 % and 99.5 %, respectively. Therefore, most regenerative anemias and cases of RWA did not have a combined iMCV+dMCHC. To avoid overlooking potential illness, RETIC should be evaluated regardless of whether patients have anemia or not.

Identification of a lactylation-related gene signature to characterize subtypes of hepatocellular carcinoma using bulk sequencing data.

Background: Prior studies indicate that lactylation regulates various biological mechanisms within cancer. However, lactylation-related genes (LRGs) have been found to have limited value in predicting the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to review HCC LRGs using data from The Cancer Genome Atlas (TCGA). Methods: The RNA sequencing data and related clinical information of patients with HCC patients were collected from the TCGA database. A total of 20 LRGs were selected and bioinformatics analysis was performed. A consistency cluster analysis was conducted to classify the HCC tumors. Using a lactylation-related model of HCC, prognosis, immune cell infiltration, and immunotherapy was evaluated. Results: A total of 4,378 genes were associated with prognosis. Twenty LRGs (i.e., ACIN1, RAN, PPP1CB, ALDOB, SUMO2, THOC2, HDAC1, SF3A1, SF3B1, HNRNPM, PPP1CC, SRRM1, PRPF6, HDAC2, H2AFV, ALYREF, H2AFZ, H2AFX, HNRNPK, and MAGOH) were identified. The 20 LRGs were used to divide TCGA-HCC patients into low-risk (G1) and high-risk (G2) categories. The upregulated genes in the G1 group primarily participate in the p53 signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cell cycle, while the downregulated genes primarily participate in the glycolysis/gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. The box plots showed a significant difference in the immune cell populations, with a higher abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells in the G1 than the G2 HCC samples. Further, the box plots showed higher expression levels of seven of the eight immune checkpoint inhibitor (ICI)-related genes in the G1 HCC samples than the G2 samples. There was a significant disparity in the cancer stem cell (CSC) scores between the G1 and G2 TCGA-HCC patients. Additionally, the G1 TCGA-HCC patients had higher tumor immune dysfunction and exclusion (TIDE) scores than the G2 TCGA-HCC patients. The prognosis of the HCC patients was also predicted using a six-LRG model, comprising HDAC2, SRRM1, SF3B1, HDAC1, THOC2, and PPP1CB. Conclusions: Strong correlation between LRGs and tumor classification as well as immunity in patients with HCC was identified. LRG signatures serve as reliable prognostic markers for HCC.

Impact of intravenous steroids on subjective recovery quality after surgery: A meta-analysis of randomized clinical trials.

STUDY OBJECTIVE: Quality of postoperative recovery is a crucial aspect of perioperative care. This meta-analysis aimed to evaluate the efficacy of intravenous steroids in improving the quality of recovery (QoR) after surgery, as measured by validated QoR scales. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. INTERVENTION: The use of a single dose of intravenous steroids as a supplement to general anesthesia. PATIENTS: Adult patients undergoing surgery. MEASUREMENTS: A literature search was conducted using electronic databases (e.g., MEDLINE and Embase) from their inception to June 2024. Randomized controlled trials (RCTs) comparing intravenous steroids with placebo or no treatment in adult patients undergoing surgery under general anesthesia were included. The primary outcome was the QoR scores on postoperative days (POD) 1 and 2-3, as assessed by validated QoR scales (QoR-15 and QoR-40). Secondary outcomes included QoR dimensions, analgesic rescue, pain scores, and postoperative nausea and vomiting (PONV). MAIN RESULTS: Eleven RCTs involving 951 patients were included in this study. The steroid group showed significant improvements in global QoR scores on POD 1 (standardized mean difference [SMD]: 0.52; 95 % confidence interval[CI]: 0.22 to 0.82; P = 0.0007) and POD 2-3 (SMD: 0.50; 95 % CI: 0.19 to 0.81; P = 0.001) compared to the control group. Significant improvements were also observed in all QoR dimensions on POD 1, with the effect sizes ranging from small to moderate. Intravenous steroids also significantly reduced the analgesic rescue requirements (RR: 0.77; 95 % CI: 0.67 to 0.88; P = 0.0003), postoperative pain scores (SMD: -0.41; 95 % CI: -0.68 to -0.14; P = 0.003), and PONV incidence (RR: 0.73; 95 % CI: 0.56 to 0.95; P = 0.02). CONCLUSIONS: Intravenous administration of steroids significantly improved QoR after surgery. The benefits of steroids extend to all dimensions of QoR and important clinical outcomes such as analgesic requirements, pain scores, and PONV. These findings support the use of steroids as an effective strategy to enhance the postoperative recovery quality.

Predictive value of polygenic risk score for prostate cancer incidence and prognosis in the Han Chinese.

Although prostate cancer is a common occurrence among males, the relationship between existing risk prediction models remains unclear. The objective of this hospital-based retrospective study is to investigate the impact of polygenic risk scores (PRSs) on the incidence and prognosis of prostate cancer in the Han Chinese population. A total of 24,778 male participants including 903 patients with prostate cancer at Taichung Veterans General Hospital were enrolled in the study. PRS was calculated using 269 single nucleotide polymorphisms and their corresponding effect sizes from the polygenic score catalog. The association between PRS and the risk prostate cancer was evaluated using Cox proportional hazards regression model. Among the 24,778 participants, 903 were diagnosed with prostate cancer. The risk of prostate cancer was significantly higher in the highest quartile of PRS distribution compared to the lowest (hazard ratio = 4.770, 95% CI = 3.999-5.689, p < 0.0001), with statistical significance across all age groups. Patients in the highest quartile were diagnosed with prostate cancer at a younger age (66.8 ± 8.3 vs. 69.5 ± 8.8, p = 0.002). Subgroup analysis of patients with localized or stage 4 prostate cancer showed no significant differences in biochemical failure or overall survival. This hospital-based cohort study observed that a higher PRS was associated with increased susceptibility to prostate cancer and younger age of diagnosis. However, PRS was not found to be a significant predictor of disease stage and prognosis. These findings suggest that PRS could serve as a useful tool in prostate cancer risk assessment.

Outbreak preparedness and response strategies in ASEAN member states: a scoping review.

Objectives: The 21st century has witnessed significant disease outbreaks with severe impact in Association of Southeast Asian Nations (ASEAN) countries, including SARS, H1N1, H5N1, and COVID-19. This review aimed to compile and analyze outbreak preparedness and response strategies, highlighting the success of coordinated multi-sectoral approaches and policy responses within the ASEAN region. Methods: The protocol for this review was registered on the Open Science Framework and PROSPERO. A systematic analysis of publications from the 2002-2022 period was conducted following PRISMA guidelines on 4522 records retrieved from PubMed, CINAHL, Web of Science, and Scopus. The titles and abstracts were screened, and 229 articles were selected for full-text screening. Finally, 34 articles were included in this review. Results: Four preparedness pillars were identified: governance and stewardship, disease detection, disease prevention, and health care management. The pillars were crucial in preparing for and responding to the COVID-19 pandemic. Coordinated responses among the ASEAN countries and local and international stakeholders were reported. Conclusions: The findings emphasize that understanding the transmission dynamics of infectious diseases is paramount for effective disease prevention, surveillance, and timely response efforts to prevent the next pandemic. A well-coordinated multi-country and multi-agency policy response and understanding the different disease management models are crucial in addressing future outbreaks in the region. Future post-pandemic publications will shed more light on lessons learned and preparedness and response plans for future pandemics.

Evaluation of the quality and readability of ChatGPT responses to frequently asked questions about myopia in traditional Chinese language.

Introduction: ChatGPT can serve as an adjunct informational tool for ophthalmologists and their patients. However, the reliability and readability of its responses to myopia-related queries in the Chinese language remain underexplored. Purpose: This study aimed to evaluate the ability of ChatGPT to address frequently asked questions (FAQs) about myopia by parents and caregivers. Method: Myopia-related FAQs were input three times into fresh ChatGPT sessions, and the responses were evaluated by 10 ophthalmologists using a Likert scale for appropriateness, usability, and clarity. The Chinese Readability Index Explorer (CRIE) was used to evaluate the readability of each response. Inter-rater reliability among the reviewers was examined using Cohen's kappa coefficient, and Spearman's rank correlation analysis and one-way analysis of variance were used to investigate the relationship between CRIE scores and each criterion. Results: Forty-five percent of the responses of ChatGPT in Chinese language were appropriate and usable and only 35% met all the set criteria. The CRIE scores for 20 ChatGPT responses ranged from 7.29 to 12.09, indicating that the readability level was equivalent to a middle-to-high school level. Responses about the treatment efficacy and side effects were deficient for all three criteria. Conclusions: The performance of ChatGPT in addressing pediatric myopia-related questions is currently suboptimal. As parents increasingly utilize digital resources to obtain health information, it has become crucial for eye care professionals to familiarize themselves with artificial intelligence-driven information on pediatric myopia.

Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine.

OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.

Directed crystalline symmetry transformation of blue-phase liquid crystals by reverse electrostriction.

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials.

Shared decision-making, treatment decision regret, and vision-related quality of life among parents of children with myopia: An online survey in Taiwan.

OBJECTIVES: To investigate the relationships among myopia treatment, decision regret, shared decision-making, and vision-related quality of life among parents of 6-12-year-old children with myopia. METHODS: An online Google Forms questionnaire was developed using a cross-sectional design and distributed between January 16 and August 22, 2023. Parents of 6-12-year-old children with myopia were recruited through school nurses working in Taiwan. The children's and parents' demographic data were collected. Study instruments included the Decisional Regret Scale, Shared Decision-Making, and Vision-Related Quality of Life questionnaires. Multivariable linear regression analysis was used to identify factors influencing vision-related quality of life. RESULTS: Of 350 parents contacted, 314 questionnaires were analyzed. Among the respondents, 77.39 % (n = 243) were mothers, and most were aged >40 years. The mean age of children at myopia diagnosis was 7.12 ± 1.24 years; 46.50 % had < - 1.0 diopters of refractive error. Atropine eye drops were the primary treatment; 17.71 % of children were prescribed orthokeratology for myopia control. Parents reported low levels of decision regret and moderate levels of shared decision-making and vision-related quality of life. Children's age, use of orthokeratology lenses, decision regret, and shared decision-making significantly influenced the vision-related quality of life reported by the parents, accounting for 22.5 % of the variance. CONCLUSION: The study's findings emphasize the importance of addressing decision regret and promoting shared decision-making in myopia treatment. Eye care professionals should discuss treatment options thoroughly before making decisions. Through shared decision-making, parents can make informed choices about treatments based on a comprehensive understanding of the benefits and drawbacks, ultimately benefitting children's vision health.

Prognostic Significance of VAV3 Gene Variants and Expression in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is characterized by high mortality and morbidity rates. Vav guanine nucleotide exchange factors (VAVs), crucial for signal transduction between cell membrane receptors and intracellular mediators, have been implicated in carcinogenesis. However, their potential prognostic value in RCC remains unclear. The impact of 150 common VAV polymorphisms on RCC risk and survival was investigated in a cohort of 630 individuals. Publicly available gene expression datasets were utilized to analyze VAV gene expression in relation to patient outcomes. The VAV3 rs17019888 polymorphism was significantly associated with RCC risk and overall survival after adjusting for false discovery rates. Expression quantitative trait loci analysis revealed that the risk allele of rs17019888 is linked to reduced VAV3 expression. Analysis of 19 kidney cancer gene expression datasets revealed lower VAV3 expression in RCC tissues compared to normal tissues, with higher expression correlating with better prognosis. Gene set enrichment analysis demonstrated that VAV3 negatively regulates the ubiquitin-proteasome system, extracellular matrix and membrane receptors, inflammatory responses, matrix metalloproteinases, and cell cycle pathways. Furthermore, elevated VAV3 expression was associated with increased infiltration of B cells, macrophages, and neutrophils into the RCC tumor microenvironment. Our findings suggest that VAV3 gene variants influence RCC risk and survival, contributing to a favorable prognosis in RCC.

Luteolin Inhibits Indoxyl Sulfate-Induced ICAM-1 and MCP-1 Expression by Inducing HO-1 Expression in EA.hy926 Human Endothelial Cells.

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

Blood pressure variability and prognostic significance in traumatic brain injury: analysis of the eICU-CRD database.

BACKGROUND: Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI. METHODS: We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis. RESULTS: We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; ptrend<0.001). CONCLUSION: Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development.

Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects. This systematic review aimed to comprehensively analyze the global epidemiology and research advancements of NiV to identify the key knowledge gaps in the literature. Articles searched using literature databases, namely PubMed, Scopus, Web of Science, and Science Direct yielded 5,596 articles. After article screening, 97 articles were included in this systematic review, comprising 41 epidemiological studies and 56 research developments on NiV. The majority of the NiV epidemiological studies were conducted in Bangladesh, reflecting the country's significant burden of NiV outbreaks. The initial NiV outbreak was identified in Malaysia in 1998, with subsequent outbreaks reported in Bangladesh, India, and the Philippines. Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India. However, the availability of NiV genome sequences remains limited, particularly from Malaysia and India. Mortality rates also vary according to the country, exceeding 70% in Bangladesh, India, and the Philippines, and less than 40% in Malaysia. Understanding these differences in mortality rate among countries is crucial for informing NiV epidemiology and enhancing outbreak prevention and management strategies. In terms of research developments, the majority of studies focused on vaccine development, followed by phylogenetic analysis and antiviral research. While many vaccines and antivirals have demonstrated complete protection in animal models, only two vaccines have progressed to clinical trials. Phylogenetic analyses have revealed distinct clades between NiV Malaysia, NiV Bangladesh, and NiV India, with proposals to classify NiV India as a separate strain from NiV Bangladesh. Taken together, comprehensive OneHealth approaches integrating disease surveillance and research are imperative for future NiV studies. Expanding the dataset of NiV genome sequences, particularly from Malaysia, Bangladesh, and India will be pivotal. These research efforts are essential for advancing our understanding of NiV pathogenicity and for developing robust diagnostic assays, vaccines and therapeutics necessary for effective preparedness and response to future NiV outbreaks.

Synergistic ROS Generation via Core-Shell Nanostructures with Increased Lattice Microstrain Combined with Single-Atom Catalysis for Enhanced Tumor Suppression.

This study emphasizes the innovative application of FePt and Cu core-shell nanostructures with increased lattice microstrain, coupled with Au single-atom catalysis, in significantly enhancing •OH generation for catalytic tumor therapy. The combination of core-shell with increased lattice microstrain and single-atom structures introduces an unexpected boost in hydroxyl radical (•OH) production, representing a pivotal advancement in strategies for enhancing reactive oxygen species. The creation of a core-shell structure, FePt@Cu, showcases a synergistic effect in •OH generation that surpasses the combined effects of FePt and Cu individually. Incorporating atomic Au with FePt@Cu/Au further enhances •OH production. Both FePt@Cu and FePt@Cu/Au structures boost the O2 → H2O2 → •OH reaction pathway and catalyze Fenton-like reactions. This enhancement is underpinned by DFT theoretical calculations revealing a reduced O2 adsorption energy and energy barrier, facilitated by lattice mismatch and the unique catalytic activity of single-atom Au. Notably, the FePt@Cu/Au structure demonstrates remarkable efficacy in tumor suppression and exhibits biodegradable properties, allowing for rapid excretion from the body. This dual attribute underscores its potential as a highly effective and safe cancer therapeutic agent.

Improving the Purity of Extracellular Vesicles by Removal of Lipoproteins from Size Exclusion Chromatography- and Ultracentrifugation-Processed Samples Using Glycosaminoglycan-Functionalized Magnetic Beads.

Extracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency. This paper introduces an optimized magnetic bead reagent, LipoMin, functionalized with glycosaminoglycans (GAGs), as a rapid alternative for LP removal during the second-step process in about 10 minutes. We evaluated LipoMin's efficacy on two sample types: (a) EV fractions isolated by size exclusion chromatography (SEC + LipoMin) and (b) the pellet obtained from ultracentrifugation (UC + LipoMin). The workflow is remarkably simple, involving a 10 min incubation with LipoMin followed by magnetic separation of the LP-depleted EV-containing supernatant. Results from enzyme-linked immunosorbent assay (ELISA) revealed that LipoMin removes 98.2% ApoB from SEC EV fractions, comparable to the LP removal ability of DG in the SEC + DG two-step process. Importantly, the EV yield (CD81 ELISA) remained at 93.0% and Western blot analysis confirmed that key EV markers, flotillin and CD81, were not compromised. Recombinant EV (rEV), an EV reference standard, was spiked into SEC EV fractions and recovered 89% of CD81 protein. For UC + LipoMin, ApoA1 decreased by 76.5% while retaining 90.7% of CD81. Notably, both colorectal cancer (CRC) and Alzheimer's disease (AD) samples processed by SEC + LipoMin and UC + LipoMin displayed clear expression of relevant EV and clinical markers. With a 10 min workflow (resulting in a 96% time saving compared to the traditional method), the LipoMin reagent offers a rapid and efficient alternative to DG for LP depletion, paving the way for a streamlined SEC + LipoMin two-step EV isolation process.

Permeable TAD boundaries and their impact on genome-associated functions.

TAD boundaries are genomic elements that separate biological processes in neighboring domains by blocking DNA loops that are formed through Cohesin-mediated loop extrusion. Most TAD boundaries consist of arrays of binding sites for the CTCF protein, whose interaction with the Cohesin complex blocks loop extrusion. TAD boundaries are not fully impermeable though and allow a limited amount of inter-TAD loop formation. Based on the reanalysis of Nano-C data, a multicontact Chromosome Conformation Capture assay, we propose a model whereby clustered CTCF binding sites promote the successive stalling of Cohesin and subsequent dissociation from the chromatin. A fraction of Cohesin nonetheless achieves boundary read-through. Due to a constant rate of Cohesin dissociation elsewhere in the genome, the maximum length of inter-TAD loops is restricted though. We speculate that the DNA-encoded organization of stalling sites regulates TAD boundary permeability and discuss implications for enhancer-promoter loop formation and other genomic processes.