Search Results (1,130)

Alzheimer’s disease (AD) is a growing public health issue disproportionately affecting adults 65 years and older. This growing trend is accompanied by rising economic, social, emotional, and physical costs, both for patients and their caregivers. As the U.S. population ages, understanding disparities in AD prevalence particularly by gender and age has become increasingly important, particularly in high-burden states like Illinois. This review focuses on gender and age disparities in AD, with a specific emphasis on Illinois. This review integrates national and global trends with state-specific projections and explores modifiable and non-modifiable risk factors that may contribute to these disparities. We analyzed projections from the Illinois Department of Public Health and the Alzheimer’s Association to assess AD prevalence by gender and age across Illinois’ 102 counties from 2020 to 2030, disaggregated by gender and age. Rates were compared with U.S. and global trends. Risk factors such as diabetes, education, access to care, and socioeconomic status were reviewed in the context of these disparities. Women consistently show higher AD prevalence across age groups and regions, with the greatest increase in cases is projected among adults aged 75 to 84 years, particularly in regions with higher women populations and social vulnerability. If unaddressed, risk factors like lower education, rural residency, and limited healthcare access may worsen these disparities. Addressing them requires focused public health efforts that combine early screening, caregiver support, and regional resource allocation. Illinois serves as a case study for targeted interventions applicable to broader national strategies. Full article

The inherent complexity and heterogeneity of tumors pose substantial challenges for the development of effective oncology therapeutics. Organoids, three-dimensional (3D) in vitro models, have become essential tools for predicting therapeutic responses and advancing precision oncology, with established correlations to clinical outcomes in patient-derived models. These systems have transformed preclinical drug screening by bridging the gap between conventional two-dimensional (2D) cultures and in vivo models, preserving tumor histopathology, cellular heterogeneity, and patient-specific molecular profiles. Despite their potential, limitations in tumor organoid biology, including inter-batch variability and microenvironmental simplification, can undermine their reliability and scalability in large-scale drug screening. To overcome these challenges, the integration of advanced technologies such as artificial intelligence (AI), automated biomanufacturing, multi-omics analytics, and vascularization strategies has been explored. This review highlights the “Organoid plus and minus” framework, which combines technological augmentation with culture system refinement to improve screening accuracy, throughput, and physiological relevance. We are convinced that the future of drug development hinges on the convergence of these multidisciplinary technologies with standardized biobanking and co-clinical validation frameworks. This integration will position organoids as a cornerstone for personalized drug discovery and therapeutic optimization, ultimately advancing the development of efficacy in oncology. Full article

Deployment of resistant barley cultivars is the most cost-effective and environmentally responsible strategy to manage barley leaf rust caused by Puccinia hordei. Gene predictions based on screening of germplasm with an array of well-characterised pathotypes and application of molecular markers serve as a pivotal step for identification, characterisation, and deploying resistance in breeding programmes. We evaluated 77 barley genotypes from 17 countries using an array of diverse P. hordei pathotypes and molecular markers to predict resistance gene identities. Evaluation and resistance analysis of the panel determined four known all-stage resistance (ASR) genes—Rph2, Rph3, Rph9.am, and Rph25 present individually or in combination, with Rph3 being the most common (33% of entries) and Rph2 the second most frequent (9%). Three entries, CG55, CG56, and CG57, exhibited low infection to all tested pathotypes and were negative for markers associated with Rph7, Rph15, and Rph28, potentially carrying novel uncharacterised resistance. In addition to ASR, our studies demonstrated that the core panel had a high prevalence of adult plant resistance (APR) to P. hordei, occurring in ~83% of entries. By employing markers linked to APR, we were able to partition known APR with Rph24 found in the most lines (60%), followed by Rph23 (17%), Rph20 (14%), and uncharacterised (9%) either individually or in combination. The resistance sources identified in this study can be effectively utilised and combined by breeding programmes to diversify their resistance gene pool. Our study also revealed the virulence and avirulence profiles of 12 Australian P. hordei pts to catalogued Rph genes, providing pathologists and breeders with insights into combining genes relevant to their breeding regions and pathogen shifts. Full article

Salmonella is a major zoonotic pathogen and phage cocktails offer a novel strategy against its infections. This study aimed to characterize Salmonella phages and assess the efficacy of various phage combinations, both in vitro and in vivo. Three phages (PJN012, PJN042, PJN065) were isolated, showing stability across a broad range of temperatures and pH values, and lacking genes associated with lysogenicity, virulence, and antibiotic resistance. Combined with two known phages (PJN025, vB_SalS_JNS02), they formed cocktails tested for lytic activity against S. Enteritidis and S. Typhimurium. Phage cocktails (comprising 2–5 phages) that demonstrated efficacy in vitro were validated using Galleria mellonella models. For S. Enteritidis strain 015, prophylactic cocktail C18 increased larval survival to 90% at 48 h (vs. 3% control). For S. Typhimurium strain 024, phage cocktail 26 showed the best therapeutic effect when co-injected with the bacterium, with a survival rate of up to 85% at 96 h, compared to 30% in the positive control group. Biofilm assays showed cocktails inhibited formation more effectively (e.g., at 24 h, C14 and C17 reduced biofilm formation by 93.74% and 94.21%, respectively) than removed established ones. The cocktails depended on bacterial type, phage genera, combinations, and incubation time. Robust in vitro screening remains crucial for optimizing phage formulations despite potential in vivo discrepancies. Full article

Artificial intelligence (AI) often suffers from high energy consumption and complex deployment in resource-constrained environments, leading to a structural mismatch between capability and deployability. This review takes two representative scenarios—energy-first and performance-first—as the main thread, systematically comparing cloud, edge, and fog/cloudlet/mobile edge computing (MEC)/micro data center (MDC) architectures. Based on a standardized literature search and screening process, three categories of miniaturization strategies are distilled: redundancy compression (e.g., pruning, quantization, and distillation), knowledge transfer (e.g., distillation and parameter-efficient fine-tuning), and hardware–software co-design (e.g., neural architecture search (NAS), compiler-level, and operator-level optimization). The purposes of this review are threefold: (1) to unify the “architecture–strategy–implementation pathway” from a system-level perspective; (2) to establish technology–budget mapping with verifiable quantitative indicators; and (3) to summarize representative pathways for energy- and performance-prioritized scenarios, while highlighting current deficiencies in data disclosure and device-side validation. The findings indicate that, compared with single techniques, cross-layer combined optimization better balances accuracy, latency, and power consumption. Therefore, AI miniaturization should be regarded as a proactive method of structural reconfiguration for large-scale deployment. Future efforts should advance cross-scenario empirical validation and standardized benchmarking, while reinforcing hardware–software co-design. Compared with existing reviews that mostly focus on a single dimension, this review proposes a cross-level framework and design checklist, systematizing scattered optimization methods into reusable engineering pathways. Full article

N-Acetylneuraminic acid (Neu5Ac), the predominant form of sialic acids (Sias), is extensively utilized in the food, pharmaceutical, and cosmetic industries. Microbial fermentation serves as a critical production method for its economical, eco-friendly, and scalable production. Escherichia coli and Bacillus subtilis, as primary industrial workhorses for Neu5Ac production, have been extensively investigated owing to their well-characterized genetic frameworks and mature molecular toolkits. Nevertheless, the intricate regulatory networks inherent to microbial systems present formidable obstacles to the high-efficiency biosynthesis of Neu5Ac. This review delineates the genetic and molecular mechanisms underlying Neu5Ac biosynthesis in both E. coli and B. subtilis. Furthermore, the rational and irrational strategies for constructing Neu5Ac microbial cell factories are systematically summarized, including the application of rational metabolic engineering to relieve feedback regulation, reconfigure metabolic networks, implement dynamic regulation, and optimize carbon sources; as well as the use of irrational strategies including directed evolution of key enzymes and high-throughput screening based on biosensors. Finally, this review addresses current challenges in Neu5Ac bioproduction and proposes integrative solutions combining machine learning with systems metabolic engineering to advance the construction of high-titer Neu5Ac microbial cell factory and the refinement of advanced fermentation technologies. Full article

Glioblastoma multiforme (GBM) is a common malignancy with poor prognosis, and exhausted T (TEX) cells, a subset of T cells characterized by progressive loss of effector functions, play a critical role in its progression. This study aimed to investigate the impact of TEX-related genes on immune function, prognosis, and drug sensitivity in GBM through multiomics analysis. Initially, we identified a novel set of TEX-related genes specific to GBM and screened hub genes (CCL5, IL18, CXCR6, FCER1G, TNFSF13B) using conventional statistical methods combined with machine learning. A prognostic risk model was subsequently constructed based on TCGA data and validated in the CGGA cohort. Single-cell and pharmacogenomic analyses revealed significant differences in tumor microenvironment composition and drug sensitivity between risk groups. Notably, Palbociclib emerged as a potential therapeutic agent targeting the novel discovered biomarker CCL5. RT-qPCR results showed that T cells with low CCL5 expression exhibited reduced expression of immune checkpoint-related genes (PD1, TIM3, LAG3) and increased expression of CD28, suggesting enhanced immune function. In conclusion, our findings highlight five hub genes as prognostic markers that could stratify GBM patients with different immune landscapes and levels of drug sensitivity. Furthermore, experimental results suggest that low CCL5 expression could alleviate T cell exhaustion and represent a promising therapeutic target, offering new strategies for improving GBM prognosis. Full article

Background and Objectives: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic procedure that has demonstrated both safety and effectiveness in the treatment of obesity. By reducing the stomach’s volume without the need for surgical incisions, ESG promotes weight loss and can improve obesity-related comorbidities. However, patient responses to ESG can vary significantly. Materials and Methods: A comprehensive search was performed on PubMed, Embase, and Cochrane for studies with endoscopic sleeve gastroplasty; the main outcomes of interest are BMI, weight loss, and postinterventional complications. The search strategy employed a combination of keywords and Medical Subject Heading (MeSH) terms, including “endoscopic sleeve gastroplasty,” “endoscopy,” and “overweight”. To ensure the thoroughness of the review, additional manual searches of key journals and the reference lists of identified studies were performed. Grey literature, such as dissertations and conference abstracts, meta-analysis, and systematic reviews, was excluded to maintain a focus on peer-reviewed evidence. Duplicate records were identified and removed using Rayyan software to streamline the screening process. The I2 test was employed for heterogeneity assessment, while the risk of bias was evaluated utilizing ROBINS-I. Results: Our literature search resulted in the inclusion of 38 studies. Endoscopic sleeve gastroplasty for weight loss is important since it is more effective than pharmacological treatments and lifestyle changes and presents lower adverse event rates compared to bariatric surgery. Long-term weight loss outcomes varied, with total body weight loss ranging from 16% to 20.9% over a period from 2 to 5 years, while excess weight loss ranged from 13% to 79%. Revisional procedures showed higher failure rates, with up to 34.3% of patients experiencing insufficient weight loss. Most interventions led to clinically significant and sustained weight loss, though variability in outcomes highlights the need for further research to optimize long-term weight management strategies. Conclusions: Endoscopic sleeve gastroplasty (ESG) emerges as a promising minimally invasive option for weight loss, offering significant improvements in both weight reduction and obesity-related comorbidities, such as diabetes, hypertension, and dyslipidemia. Full article

Background/Objectives: To delineate integrated lifestyle profiles combining physical activity (PA) and dietary intake (DI) and test their links with lower limb injury in physically active young adults. Methods: We analyzed a cross-sectional convenience sample of university students (men: n = 91, 20.5 ± 1.0 years; women: n = 118, 20.3 ± 0.8 years). PA (IPAQ) and DI (QEB) were assessed alongside self-reported injuries. Latent class modeling derived PA–DI profiles. Injury prevalence across profiles was compared (χ²), and logistic regression examined injury odds adjusting for sex, age, and BMI. Results: Four profiles emerged. Two reflected less healthy patterns (Profiles 2–3) and two healthier ones (Profiles 1, 4). Profile 4 showed higher vegetables/legumes/fermented milk and lower fast food/sugary drinks; Profile 3 combined greater sitting and fried/sweetened items with lower walking/milk intake. Overall injury prevalence was 56.9%, ranging from 44.1% (Profile 2) to 66.7% (Profile 4 exceeded Profile 2 in pairwise comparison (χ² (1) = 5.08, p = 0.024)). In adjusted models, men had higher injury odds (OR = 1.94, 95% CI: 1.09–3.48, p = 0.025); profile membership was not independently predictive, and profile × sex interactions were null. Conclusions: Young adults cluster into distinct PA–DI patterns that differ behaviorally, but sex—rather than profile—was the most consistent correlate of injury. Prevention should integrate lifestyle screening with sex-specific strategies. Full article

Background/Objectives: The lack of canonical biomarkers and strategies to target radioresistance contribute to poor patient outcomes in triple-negative breast cancer (TNBC). Identifying and targeting novel radioresistance genes will benefit in enhancing radiotherapy response and treatment outcomes in TNBC patients. Methods: A genome-wide CRISPR screen was performed to identify radioresistance genes in the TNBC cell line. An in vitro clonogenic assay was used to assess the antiproliferative effects of Artemis knockout or pharmacologic inhibition of Artemis, either alone or in combination with RT. Tumor doubling time and animal survival were assessed using an in vivo xenograft model. RNA-seq analysis was performed to identify genes and pathways deregulated under Artemis knockout conditions, both alone and in combination with RT. Cellular senescence was evaluated using a β-galactosidase assay. Results: Our CRISPR screen identified Artemis as a top hit in RT-treated TNBC cells, whose depletion led to radiosensitization in TNBC. Artemis knockout significantly reduced cell proliferation and enhanced the antiproliferative effects of RT in vitro. Compared to mice-bearing control MDA-MB-231 xenografts, Artemis knockout exhibited prolonged survival that was further enhanced with RT. Bulk RNA-sequencing indicated that the antiproliferative and radiosensitization effects of Artemis depletion were mediated by the activation of cellular senescence which was confirmed with a β-galactosidase assay. Conclusions: Taken together, our results highlight the critical role of Artemis in TNBC cell proliferation and response to radiation. Our findings identify Artemis as a potential biomarker indicative of sensitivity to radiation and a putative target that could be inhibited to enhance the efficacy of RT in TNBC. Full article

Current standard treatments for osteosarcoma have not been changed for decades and have limited and variable success. The advancement of precision medicine technologies, along with the drug-repurposing and fast drug-screening methodologies available, has opened new avenues for the development of more effective therapeutic strategies. In this study, we evaluated the effectiveness of halogenated boroxine (HB) and dextran-coated cerium oxide nanoparticles—DexCeNPs (SD2)—in an in vitro osteosarcoma model. Both agents were tested individually and in combination. The research encompassed assessments of treatment-related cytotoxicity and cell viability, oxidative stress, and apoptotic and necrotic responses, as well as the effects on 3D spheroid models. The results demonstrated that the effects of HB and SD2 were strongly influenced by the dose, exposure time, and cell type. Both exhibited distinguished antitumor activity through cytotoxicity and specific reactive oxygen species (ROS) induction. The combined treatment produced modulated responses that were dependent on the treatment ratio and cell line, suggesting potential synergistic or selective interactions. Notably, the outcomes of the analysis conducted in 3D models revealed reduced toxicity toward non-tumor cells. These findings suggest the improved efficacy of HB and SD2 used in combination as a selective and novel antitumor strategy and underscore the need for further mechanistic studies at the transcriptomic and proteomic levels to elucidate the underlying pathways and clarify the mechanisms of action. Full article

Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search was conducted in July 2025 across the PubMed, Scopus, and Web of Science databases. Search terms included combinations of (chitosan scaffold) AND (growth factor OR BMP-2 OR VEGF OR FGF OR TGF-beta OR periostin OR PDGF OR IGF-1 OR EGF OR ANG-1 OR ANG-2 OR GDF-5 OR SDF-1 OR osteopontin). The study selection process followed PRISMA 2020 guidelines and the PICO framework. Out of 367 records, 226 were screened, and 17 studies met the eligibility criteria for qualitative analysis. BMP-2 was the most frequently investigated growth factor, studied in both in vitro and in vivo models, with rats and rabbits as the most common animal models. Scaffold compositions varied, incorporating hydroxyapatite, heparin, polyethylene glycol diacrylate, octacalcium phosphate-mineralized graphene, silk fibroin, and aloe vera. Growth factors were introduced using diverse methods, including microspheres, chemical grafting, covalent coupling, protein carriers, and nanohydroxyapatite mesopores. Most studies reported enhanced bone regeneration, although differences in models, scaffold composition, and delivery methods preclude definitive conclusions. The addition of growth factors generally improved osteoblast proliferation, angiogenesis, bone density, and expression of osteogenic markers (RunX2, COL1, OPN, OCN). Combining two bioactive agents further amplified osteoinduction and vascularization. Sustained-release systems, particularly those using heparin or hydroxyapatite, prolonged biological activity and improved regenerative outcomes. In conclusion, functionalization of chitosan-based scaffolds with growth factors shows promising potential for bone regeneration. Controlled-release systems and combinations of different bioactive molecules may offer synergistic effects on osteogenesis and angiogenesis. Further research should focus on optimizing scaffold compositions and delivery methods to tailor bioactive agent release for specific clinical applications. Full article

Student exam pass prediction (EPP) is a key task in educational assessment and can help teachers identify students’ learning obstacles in a timely manner and optimize teaching strategies. However, existing EPP models, although capable of providing quantitative analysis, suffer from issues such as complex algorithms, poor interpretability, and unstable accuracy. Moreover, the evaluation process is opaque, making it difficult for teachers to understand the basis for scoring. To address this, this paper proposes an approximate belief rule base (ABRB-a) student examination passing prediction method based on adaptive reference point selection using symmetry. Firstly, a random forest method based on cross-validation is adopted, introducing intelligent preprocessing and adaptive tuning to achieve precise screening of multi-attribute features. Secondly, reference points are automatically generated through hierarchical clustering algorithms, overcoming the limitations of traditional methods that rely on prior expert knowledge. By organically combining IF-THEN rules with evidential reasoning (ER), a traceable decision-making chain is constructed. Finally, a projection covariance matrix adaptive evolution strategy (P-CMA-ES-M) with Mahalanobis distance constraints is introduced, significantly improving the stability and accuracy of parameter optimization. Through experimental analysis, the ABRB-a model demonstrates significant advantages over existing models in terms of accuracy and interpretability. Full article

We report a novel tablet-based reverse titration system for rapid, point-of-use measurement of water hardness, overcoming key limitations of conventional EDTA titration. Reagents are encapsulated in pullulan matrix giving two separate tablets. The first tablet contains the Eriochrome black T (EBT) and N-cyclohexyl-3-aminopropanesulfonic acid (CAPS) buffer, while the second encapsulates ethylenediaminetetraacetic acid (EDTA) disodium salt dihydrate. The system employs a trimodal detection strategy: qualitative screening via immediate color change with the EBT tablet, semi-quantitative estimation through combined tablet dissolution and adjusting the sample volume to a reference level, and quantitative determination using reverse titration, where water is gradually added until the red wine endpoint appears. This approach enhances interference tolerance from competing metal ions and improves accuracy over traditional methods. Testing with real water samples showed excellent agreement with standard titration. The tablets remain stable for over seven months, and the system eliminates the need for skilled personnel, laboratory equipment, or bulky instrumentation. This low-cost, user-friendly, and interference-tolerant platform enables rapid and accurate water hardness assessment at the point of use. Full article

The excessive use of irrigation water and fertilizers in agriculture raises serious environmental concerns, emphasizing the need for more sustainable practices. Screening genotypes with reduced nutrient and water requirements, combined with favorable responses to plant growth-promoting rhizobacteria (PGPR), offers a promising strategy for developing more sustainable farming systems. Seven sweet pepper genotypes (Capsicum annuum L.) were evaluated under six treatments, involving two fertilization levels (100% and 50% standard dose), two irrigation regimes (100% and 75% full irrigation), and PGPR inoculation applied under reduced fertilization. Yield, fruit weight, rhizosphere enzymatic activities, and soluble sugars in green and red fruits were evaluated. The genotype effect contributed significantly to all traits. Combined reductions in fertilizer and irrigation decreased average yield by 21.7%, while PGPR did not fully compensate for these losses. Alkaline phosphomonoesterase activity increased by 22.9% under low fertilization, whereas averaged catalase and dehydrogenase remained relatively stable regardless of PGPR. In green fruits, PGPR inoculation under combined stress conditions increased glucose and fructose concentrations by 11.6% and 13.9%, respectively, compared to uninoculated stressed plants, although sucrose decreased. At fully ripe stage, sugar composition was less responsive to treatments. These findings underscore the importance of genotype evaluation and the exploitation of genotype × treatment interactions in peppers breeding for sustainable farming. Full article