Search Results (192,837)

Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying mechanism—particularly whether chemotherapy functions as a broad antigen-releasing agent enabling TLR-driven immune amplification—remained undefined. Methods: Using murine models of breast (4T1), melanoma (B16-F10), and colorectal cancer (CT26), we tested multiple chemotherapeutic classes combined with CR108. We quantified intratumoral and systemic soluble TAs, antigen presentation and cross-priming by antigen-presenting cells, tumor-infiltrating lymphocytes, and cytokine production by flow cytometry/ICS. T-cell receptor β (TCRβ) repertoire dynamics in tumor-draining lymph nodes were profiled to assess amplitude and breadth. Tumor microenvironment remodeling was analyzed, and public datasets (e.g., TCGA basal-like breast cancer) were interrogated for expression of genes linked to TA generation/processing and peptide loading. Results: Using cisplatin + CR108 in 4T1 as a benchmark, we demonstrate that diverse chemotherapies—especially platinum agents—broadly increase the repertoire of soluble tumor antigens available for immune recognition. Across regimens, chemotherapy combined with CR108 increased T-cell recognition of candidate TAs and enhanced IFN-γ⁺ CD8⁺ responses, with platinum agents producing the largest expansions in soluble TAs. TCRβ sequencing revealed increased clonal amplitude without loss of repertoire breadth, indicating focused yet diverse antitumor T-cell expansion. Notably, therapeutic efficacy was not predicted by canonical damage-associated molecular pattern (DAMP) signatures but instead correlated with antigen availability and processing capacity. In human basal-like breast cancer, higher expression of genes involved in TA generation and antigen processing/presentation correlated with improved survival. Conclusions: Our findings establish an antigen-centric mechanism underlying chemo–TLR agonist synergy: chemotherapy liberates a broadened repertoire of tumor antigens, which CR108 then leverages via innate immune activation to drive potent, T-cell-mediated antitumor immunity. This framework for rational selection of chemotherapy partners for TLR7/8/9 agonism and support clinical evaluation to convert “cold” tumors into immunologically responsive disease. Full article

Food industry generates substantial waste, raising economic and environmental concerns. Green Chemistry (GC) highlights the extraction of nutritional and bioactive compounds as a key strategy for waste valorization, driving interest in sustainable methods to recover valuable compounds efficiently. This review evaluates the sustainability of widely used emerging extraction technologies—Microwave-, Ultrasound- and Enzyme-Assisted, as well as Supercritical Fluid Extraction—and their alignment with GC principles for agri-food waste valorization. It first outlines the principles, key parameters, and main advantages and limitations of each technique. Subsequently, sustainability is then assessed in selected studies using the Analytical GREEnness Metric Approach (AGREEprep). By calculating the greenness score (GS), this metric quantifies the adherence of extraction processes to sustainability standards. The analysis reveals variations within the same extraction method, influenced by solvent choice and operating conditions, as well as differences across the techniques, highlighting the importance of process design in achieving green and efficient valorization. Full article

The ability of common carp to withstand both short-term and long-term oxygen deprivation has been well documented; however, the potential genetic mechanisms behind common carp’s hypoxia response remain unclear. Therefore, to understand the possible genetic foundation of their response to hypoxia, comparative genomic analyses were conducted among six common carp varieties: Color, Songpu, European, Yellow, Mirror, and Hebao common carps. We identified 118 single-copy orthologous positively selected genes (PSGs) (dN/dS > 1) in all common carps under study, with GO functions directly related to the cellular responses to hypoxia in Color and European common carp PSGs, such as oxygen transport activity, oxygen binding activity, respiratory burst activity, and superoxide anion production. The Bayes Empirical Bayes (BEB) technique identified possible amino acid substitutions in mitochondrial and hypoxic genes under positive selection. Exonic and intronic structural variations (SVs) were discovered in the CYGB2 hypoxia-related gene of Color and European common carps, as well as in several mitochondrial genes, including MRPL20, MRPL32, NSUN3, GUF1, TMEM17B, PDE12, ACAD6, and COX10 of Color, European, Songpu, Yellow, and Hebao common carps. Moreover, Color common carp and Songpu common carp were found to share the greatest percentage of collinear genes (49.8%), with seven Songpu common carp chromosomes (chr A2, chr A9, chr A13, chr B13, chr B15, chr B2, and chr B12) showing distinct translocation events with the corresponding chromosomes of Color common carp. Additionally, we found 570 translocation sites that contained 3572 translocation-related genes in Color common carp, some of which are directly relevant to mitochondrial and hypoxic GO functions and KEGG pathways. Our results offer strong genome-wide evidence of the possible evolutionary response of Cyprinus carpio to hypoxia, providing important insights into the potential molecular mechanisms that explain their survival in hypoxic environments and guiding future research into carp hypoxia tolerance. Full article

Oxidative stress plays a critical role in the development of various chronic diseases, leading to major health problems worldwide. There has been increasing interest in using natural antioxidants as complementary agents for maintaining redox homeostasis and assuring a healthy lifestyle. This study aimed to systematically screen the antioxidant potential and cytotoxicity profiles of 19 plant-derived extracts using both a cell-free Fenton reaction-based assay and human monocytic THP-1 cells in vitro. The radical-scavenging capacity varied markedly among the extracts, with Acalypha virginica Linnaeus (ACALYPHA), Acorus calamus Linnaeus (ACORUS), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), and Heuchera sanguinea Pursh (HEUCHERA) demonstrating strong activity in the chemical assay. In the cellular model, 15 extracts significantly reduced intracellular reactive oxygen species (ROS) levels without inducing cytotoxicity at effective concentrations. Notably, Acalypha virginica Linnaeus (ACALYPHA), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), Dianthus superbus Linnaeus subsp. superbus (DIANTHUS), Succisa pratensis Moench (SUCCISA), and Typha laxmannii Lepech (TYPHA) exhibited consistent antioxidant efficacy across multiple doses. At higher concentrations, all extracts triggered apoptosis and/or necrosis, emphasizing the importance of defining safe ranges. These findings provide a comprehensive comparative analysis of Mediterranean plant-based natural antioxidants obtained by an in vitro approach. The selected plant extracts could be considered as promising candidates for the development of strategies targeting oxidative stress-related disorders. Further investigations considering the specific phytochemical composition of each extract and in vivo validation are needed to confirm their efficacy and safety. Full article

Early chronic pancreatitis (ECP) represents a potentially reversible stage in the natural history of chronic pancreatic disease. Timely diagnosis of ECP offers a possibility for intervention, yet its diagnosis remains challenging due to nonspecific symptoms, lack of standardized criteria, and the limited diagnostic sensitivity of conventional tools. This review aims to synthesize recent advancements in the understanding, detection, and management of ECP, with a focus on innovation in imaging techniques and biomarker profiling. The goal is to facilitate earlier diagnosis and more effective patient stratification. We reviewed the literature from the past five years, including original studies, meta-analyses, and expert consensus statements, to address the current evidence across genetic, inflammatory, imaging, and biochemical domains relevant to ECP. Endoscopic ultrasound and advanced magnetic resonance techniques offer high sensitivity in detecting early parenchymal changes, although inter-observer variability and lack of standardization persist. Biomarker discovery has focused on inflammatory (IL-6, sCD163), fibrotic (TGF-β1, TIMP-1), and oxidative markers, as well as novel candidates like microRNAs. Genetic predisposition (PRSS1, SPINK1, CTRC, CPA1, CLDN2) significantly influences disease onset and progression and could enable selection of high-risk individuals. Therefore, diagnosing ECP should involve a multidisciplinary precision-based approach integrating clinical, radiologic, molecular, serologic, and genetic data for individualized risk stratification. Full article

Personalized drug selection is crucial for treating complex diseases such as Acute Myeloid Leukemia, where maximizing therapeutic efficacy is essential. Although precision medicine aims to tailor treatments to individual molecular profiles, existing machine learning models often fall short in selecting the best drug from multiple candidates. We present SEATS (Systematic Efficacy Assignment with Treatment Seats), which adapts conventional models like Random Forest and XGBoost for multiclass drug assignment by allocating probabilistic “treatment seats” to drugs based on efficacy. This approach helps models learn clinically relevant distinctions. Additionally, we assess an interpretable Optimal Decision Tree (ODT) model designed specifically for drug assignment. Trained on the BeatAML2 cohort and validated on the GDSC AML cell line dataset, integrating SEATS with Random Forest and XGBoost improved prediction accuracy and consistency. The ODT model offered competitive performance with clear, interpretable decision paths and minimal feature requirements, facilitating clinical use. SEATS reorients standard models towards personalized drug selection. Combined with the ODT framework it provides effective, interpretable strategies for precision oncology, underscoring the potential of tailored machine learning solutions in supporting real-world treatment decisions. Full article

Serious games in nursing education provide students with unique opportunities to increase knowledge and enhance decision-making and problem-solving skills. Hence, serious games from simple quizzes that test students’ knowledge to Virtual Reality simulations that gauge students’ ability skills have been developed. This evidence-based review examines the latest initiatives in serious games for nursing curriculum focusing on the design and their technological features to highlight the need of pre-selecting the appropriate elements when conceptualizing a nursing serious game. Using search algorithms in Scopus and PubMed, 1969 articles published between 2019 and 2023 were screened, resulting in 81 studies and 69 unique nursing serious games involving over 7000 nursing students. Geographical distribution of serious games, the games’ type, teaching subject, nursing courses incorporating the games, technologies embarked, and different gaming platforms/engines utilized for their development are reported. Furthermore, common gamification elements (e.g., score, avatars, and quests) and key-design features (e.g., player mode, player–game interaction, feedback provision, and failure option) are described. By reporting on the latest technological advancements, a useful guide is formed, enabling both programmers and educators to easily grasp the newest trends on serious game design and use the produced knowledge to further enhance the nursing curriculum. Full article

Background: The treatment of wounds remains a significant clinical challenge, particularly in chronic and infected wounds, where delayed healing often results in complications. Recent advances in biomaterials have highlighted the potential of polymer-based scaffolds as promising platforms for wound management due to their ability to mimic the extracellular matrix, support tissue regeneration, and provide a moist environment conducive to healing. Objectives: This review aims to provide a comprehensive overview of the recent progress in the design and application of polymer-based scaffolds loaded with essential oil (EO) components, emphasizing their role in promoting effective wound healing. Methods: Relevant literature on polymeric scaffolds and EO-based bioactive agents was systematically reviewed, focusing on studies that investigated the biological activities, fabrication techniques, and therapeutic performance of EO-loaded scaffolds in wound management. Results: Findings from recent studies indicate that EO components, particularly monoterpenoids such as thymol, carvacrol, and eugenol, exhibit remarkable antimicrobial, anti-inflammatory, antioxidant, and analgesic properties that accelerate wound healing. When incorporated into polymer matrices, these components enhance scaffold biocompatibility, antimicrobial efficacy, and tissue regeneration capacity through synergistic interactions. Conclusion: The integration of essential oil components into polymeric scaffolds represents a promising strategy for developing multifunctional wound dressings. Such systems combine the structural advantages of polymers with the therapeutic benefits of EOs, offering an effective platform for accelerating healing and preventing wound infections. Full article

As the core space for students’ daily living and learning, the quality of the indoor wind environment and air quality in dormitory buildings is particularly critical. However, existing studies often neglect natural ventilation optimization under local climatic conditions and the multidimensional evaluation of health benefits, leaving notable gaps in dormitory design. Under the Healthy China Initiative, the indoor wind environment in university dormitories directly impacts students’ health and learning efficiency. This study selects dormitory buildings in Xuzhou as the research object and employs ANSYS FLUENT 2020 software for computational fluid dynamics (CFD) simulations, combined with orthogonal experimental design methods, to systematically investigate and optimize the indoor wind environment with a focus on healthy ventilation standards. The evaluation focused on three key metrics—comfortable wind speed ratio, air age, and CO₂ concentration—considering the effects of building orientation, corridor width, and window geometry, and identifying the optimal parameter combination. After optimization based on the orthogonal experimental design, the proportion of comfortable wind speed zones increased to 44.6%, the mean air age decreased to 258 s, and CO₂ concentration stabilized at 613 ppm. These results demonstrate that the proposed optimization framework can effectively enhance indoor air renewal and pollutant removal, thereby improving both air quality and the health-related performance of dormitory spaces. The novelty of this study lies in integrating regional climate conditions with a coordinated CFD–orthogonal design approach. This enables precise optimization of dormitory ventilation performance and provides locally tailored, actionable evidence for advancing healthy campus design. Full article

Viral metagenomic next-generation sequencing (vmNGS) has transformed our capacity for the untargeted detection and characterisation of (re)emerging zoonotic viruses, surpassing the limitations of traditional targeted diagnostics. In this review, we critically evaluate the current landscape of vmNGS, highlighting its integration within the One Health paradigm and its application to the surveillance and discovery of (re)emerging viruses at the human–animal–environment interface. We provide a detailed overview of vmNGS workflows including sample selection, nucleic acid extraction, host depletion, virus enrichment, sequencing platforms, and bioinformatic pipelines, all tailored to maximise sensitivity and specificity for diverse sample types. Through selected case studies, including SARS-CoV-2, mpox, Zika virus, and a novel henipavirus, we illustrate the impact of vmNGS in outbreak detection, genomic surveillance, molecular epidemiology, and the development of diagnostics and vaccines. The review further examines the relative strengths and limitations of vmNGS in both passive and active surveillance, addressing barriers such as cost, infrastructure requirements, and the need for interdisciplinary collaboration. By integrating molecular, ecological, and public health perspectives, vmNGS stands as a central tool for early warning, comprehensive monitoring, and informed intervention against (re)emerging viral threats, underscoring its critical role in global pandemic preparedness and zoonotic disease control. Full article

Background/Objectives: Infant emotional responses during complementary feeding offer key insights into early developmental processes and feeding behaviors. AI-driven facial emotion analysis presents a novel, objective method to quantify these subtle expressions, potentially informing interventions in early childhood nutrition. We aimed to investigate how maternal and infant traits influence infants’ emotional responses during complementary feeding using an automated facial analysis tool. Methods: This multi-center study involved 117 typically developing infants (6–11 months) and their mothers. Standardized feeding sessions were recorded, and OpenFace software quantified six emotions (surprise, sadness, fear, happiness, anger, disgust). Data were normalized and analyzed via Generalized Estimating Equations to identify associations with maternal BMI, education, work status, and infant age, sex, and complementary feeding initiation. Results: Emotional responses did not differ significantly across five food groups. Infants of mothers with BMI >30 kg/m² showed greater surprise, while those whose mothers were well-educated and not working displayed more happiness. Older infants and those introduced to complementary feeding before six months exhibited higher levels of anger. Parental or infant food selectivity did not significantly affect responses. Conclusions: The findings indicate that maternal and infant demographic factors exert a more pronounced influence on infant emotional responses during complementary feeding than the type of food provided. These results highlight the importance of integrating broader psychosocial variables into early feeding practices and underscore the potential utility of AI-driven facial emotion analysis in advancing research on infant development. Full article

Monoacylglycerol lipase (MAGL) is a key serine hydrolase involved in lipid metabolism, catalyzing the hydrolysis of monoacylglycerols into free fatty acids and glycerol. MAGL plays a central role in regulating endocannabinoid signaling and lipid homeostasis, processes often dysregulated in cancer and other pathological conditions. In recent years, MAGL has emerged as a promising therapeutic target, particularly in oncology, where its inhibition has shown potential to impair tumor growth, metastasis, and inflammation-driven processes. Alongside the development of selective MAGL inhibitors, several biochemical methods have been established to measure MAGL enzymatic activity, providing essential tools for target validation and inhibitor characterization. In this review, we provide a comprehensive and critical overview of the main approaches developed for MAGL activity evaluation, including radiometric, chromatographic, colorimetric, fluorescence-based, bioluminescence-based, and activity-based protein profiling (ABPP) assays. For each method, we discuss principles, advantages, and limitations. This review aims to support researchers in the selection of the most appropriate assay strategy for their experimental needs, ultimately fostering the rapid and accurate development of novel MAGL inhibitors with potential applications in cancer therapy and metabolic disease management. Full article

Leaf rust, a devastating fungal disease caused by Puccinia triticina (Pt), severely impacts wheat quality and yield. Identifying genetic loci for wheat leaf rust resistance, developing molecular markers, and breeding resistant varieties is the most environmentally friendly and economical strategy for disease control. This study utilized a recombinant inbred line (RIL) population of Doumai and Shi4185, combined with the wheat 90 K single nucleotide polymorphisms (SNPs) chip data and maximum disease severity (MDS) of leaf rust from four environments, to identify adult plant resistance (APR) loci through linkage mapping. Additionally, kompetitive allele-specific PCR (KASP) markers suitable for breeding were developed, and genetic effects were validated in a natural population. In this study, 5 quantitative trait loci (QTL) on chromosomes 1B (2), 2A and 7B (2) were identified through inclusive composite interval mapping, and named as QLr.lfnu-1BL1, QLr.lfnu-1BL2, QLr.lfnu-2AL, QLr.lfnu-7BL1 and QLr.lfnu-7BL2, respectively, explaining 4.54–8.91% of the phenotypic variances. The resistance alleles of QLr.lfnu-1BL1 and QLr.lfnu-1BL2 originated from Doumai, while the resistance alleles of QLr.lfnu-2AL, QLr.lfnu-7BL1 and QLr.lfnu-7BL2 came from Shi4185. Among these, QLr.lfnu-1BL2, QLr.lfnu-7BL1 and QLr.lfnu-7BL2 overlapped with previously reported loci, whereas QLr.lfnu-1BL1 and QLr.lfnu-2AL are likely to be novel. Two KASP markers, QLr.lfnu-2AL and QLr.lfnu-7BL, were significantly associated with leaf rust resistance in a diverse panel of 150 wheat varieties mainly from China. Totally, 34 potential candidate genes encoded the NLR proteins, receptor-like kinases, signaling kinases and transcription factors were selected as candidate genes for the resistance loci. These findings will provide stable QTL, available breeding KASP markers and candidate genes, and will accelerate the progresses of wheat leaf rust resistance improvement through marker-assisted selection breeding. Full article

Hydrogel scaffolds have emerged as pivotal materials in regenerative medicine due to their biocompatibility, tunable mechanical properties, and ability to mimic the extracellular matrix. However, conventional fabrication techniques often lack the precision required to create complex architectures, limiting their effectiveness in tissue engineering. This review explores advanced laser-based fabrication methods, such as two-photon polymerization, laser-induced forward transfer, selective laser sintering/melting, and laser direct writing, which offer unparalleled resolution and control over scaffold geometry. These techniques enable the production of intricate 3D structures tailored to specific clinical needs, from vascular networks to patient-specific implants. We analyze the principles, advantages, and limitations of each method, highlighting their biomedical applications and the challenges of scalability, material compatibility, and cost. By bridging the gap between laboratory research and clinical implementation, laser-based technologies hold significant promise for advancing personalized medicine and tissue regeneration. Full article

Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. This review aims to consolidate current genomic data across AC subtypes and explore the clinical relevance of recurrent mutations. Methods: A systematic literature review was performed in accordance with general Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. Using search engines such as PubMed and Web of Science, we selected studies based on relevance to AC genomics using search terms such as “appendix cancer”, “appendiceal cancer”, “pseudomyxoma peritonei”, “sequencing”, “mutation”, and “genotype”. Results: AC comprises five major histologic subtypes—appendiceal neuroendocrine neoplasms (ANENs), mucinous appendiceal neoplasms (MANs), goblet cell adenocarcinomas (GCAs), colonic-type adenocarcinomas (CTAs) and signet ring cell adenocarcinomas (SRCs)—each with unique clinical behaviors and mutational profiles. Low-grade tumors, such as ANENs and MANs, frequently harbor KRAS and GNAS mutations, while high-grade subtypes, such as CTAs and SRCs, are enriched for TP53, APC, and SMAD gene alterations. GCA tumors exhibit a distinct mutational spectrum involving chromatin remodeling genes such as ARID1A and KMT2D. Compared to colorectal cancer, AC demonstrates lower frequencies of APC and TP53 mutations and a higher prevalence of GNAS mutations, consistent with a pathological divergence from CRC. Conclusions: The genomic heterogeneity of AC is commensurate with its histological complexity and has important implications for diagnosis, prognosis and treatment. While certain actionable mutations are present in a subset of tumors, large-scale genomic characterization efforts and development of subtype-specific models will be essential for advancing precision medicine in AC. Full article