Search Results (31,507)

Incorporating cyclodextrins (CDs) into ionically crosslinked polysaccharide matrices offers a promising strategy for developing well-defined, safe-by-design and biocompatible carrier systems with tunable rheological properties. In this study, β-cyclodextrin (β-CD) was functionalized with citric acid (CDC) and maleic anhydride (CDM) using solvent-free synthesis to improve compatibility with alginate hydrogels. The modified CDs were characterized by FTIR, ¹H NMR, DLS, zeta potential, and MS, confirming successful esterification (4.0 and 3.4 –OH substitution for CDC and CDM, respectively) and stable aqueous dispersion. Rheological measurements showed that native CD accelerated gelation (within approximately 30 s), while CDC and CDM delayed crosslinking (by 2 to 13 min) and reduced gel strength, narrowing the linear viscoelastic range to 0.015–0.089% strain due to competition between polycarboxylated CDs and alginate chains for Ca²⁺ ions. Vibrational prilling produced alginate microbeads with diameters of 800–1000 µm and a simultaneous increase in size and CD concentration. Hydrogels demonstrated high CD retention (>80% after 28 h) and slightly greater release of CDC and CDM than native CD. Overall, solvent-free modification of CDs with citric and maleic acids provides a sustainable approach to tailoring the gelation kinetics, viscoelasticity, and release behavior of alginate-based hydrogels, offering a versatile, food- and health-compliant platform for controlled delivery of bioactive compounds. Full article

Contact dermatitis (CD) is a common inflammatory skin condition with irritant etiology or a delayed-type hypersensitivity called allergic contact dermatitis (ACD). Contact hypersensitivity (CHS) is a widely used rodent model of ACD and similarly consists of two phases: sensitization and elicitation. To trigger CHS, low-molecular-weight haptens, such as DNFB or TNCB, are commonly applied. However, the characterization of the induced immune response remains incomplete. Our aim was to characterize the immune response after first and repeated exposures to model haptens. First exposure to DNFB or TNCB led to significant ear swelling, with DNFB causing a more pronounced effect. DNFB enhanced neutrophil infiltration, whereas TNCB led to macrophage, dendritic cell, and helper T cell accumulation. Repeated DNFB exposure did not aggravate edema significantly, while TNCB re-exposure enhanced edema formation and induced neutrophil granulocyte, dendritic cell, and helper and cytotoxic T cell accumulation. Our results demonstrate that a hapten-specific immune response is induced during both phases of CHS. A detailed understanding of allergen-specific immune responses is crucial for the appropriate selection of the model and for gaining deeper insight into the mechanisms of inflammatory skin diseases. These findings may contribute to the targeted selection of haptens. Full article

Background/Objectives: Juzentaihoto (JTT), a traditional Kampo formula composed of ten medicinal herbs, is widely prescribed in Japan for immune enhancement and general health maintenance. This exploratory, open-label pilot study aimed to evaluate the feasibility and immunomodulatory effects of JTT in cancer patients and to explore its potential mechanisms of action. Methods: Ten cancer patients received oral JTT (7.5 g/day) for 14 days, while healthy volunteers served as a reference group. Peripheral natural killer (NK) cell phenotypes and CD95 expression were analyzed by flow cytometry, and serum Fas ligand (FasL) concentrations were measured by ELISA. Complementary in vitro assays using PBS-extracted, autoclaved JTT were conducted to assess Fas/FasL-mediated apoptosis in Jurkat and primary T cells by flow cytometry and Western blotting for cleaved caspase-8 and -3. Additional experiments with staurosporine (intrinsic apoptosis) and TRAIL in OSC-19 carcinoma cells were performed to determine pathway specificity. Results: In patients, most NK-cell markers showed no statistically significant within-subject changes, although a trend-level increase in NKp46 and a significant reduction in NK-cell CD95 expression (paired p = 0.014) were observed. Between-group differences primarily reflected baseline disparities between cancer patients and healthy controls. In vitro, JTT (50–100 µg/mL) partially attenuated FasL-induced apoptosis and reduced cleaved caspase-3 without affecting cleaved caspase-8, suggesting selective downstream modulation of the extrinsic pathway. Conclusions: Within the limitations of a small, non-randomized cohort without placebo, these findings are hypothesis-generating and indicate that JTT selectively modulates Fas-mediated lymphocyte apoptosis without promoting tumor immune evasion. Further randomized trials and mechanistic studies incorporating co-culture or 3D tumor–immune models are warranted to confirm these observations and identify active constituents. Full article

Phase and band gap engineering of (CdS)_x(CuInS₂)_1−x nanomaterials is critical for their potential applications in photovoltaics and photocatalysis, yet it remains a challenge. Here, we report a precursor-mediated colloidal method for phase-control synthesis of alloyed (CdS)_x(CuInS₂)_1−x nanocrystals with tunable band gap. When CuCl, InCl₃, and Cd(AC)₂·2H₂O are used as the respective cation sources, wurtzite-structured alloyed (CdS)_x(CuInS₂)_1−x nanocrystals can be synthesized with a tunable optical band gap ranging from 1.56 to 2.45 eV by directly controlling the molar ratio of the Cd precursor. Moreover, using Cu(S₂CNEt₂)₂, In(S₂CNEt₂)₃, and Cd(S₂CNEt₂)₂ as cation sources results in alloyed (CdS)_x(CuInS₂)_1−x nanocrystals with a zinc-blende structure, demonstrating that the optical band gap of these nanocrystals can be compositionally tuned from 1.50 to 1.84 eV through precisely adjusting the molar ratio of Cd precursor. The results were validated through a comprehensive characterization approach employing XRD, TEM, HRTEM, STEM-EDS, XPS, UV-vis-NIR absorption spectroscopy, and Mott–Schottky analysis. Full article

The photocatalytic degradation of Crystal Violet (CV) using ZnO-based nanomaterials presents a promising solution for addressing water pollution caused by synthetic dyes. This review highlights the exceptional efficiency of ZnO and its modified forms—such as doped, composite, and heterostructured variants—in degrading CV under both ultraviolet (UV) and solar irradiation. Key advancements include strategic bandgap engineering through doping (e.g., Cd, Mn, Co), innovative heterojunction designs (e.g., n-ZnO/p-Cu₂O, g-C₃N₄/ZnO), and composite formations with graphene oxide, which collectively enhance visible-light absorption and minimize charge recombination. The degradation mechanism, primarily driven by hydroxyl and superoxide radicals, leads to the complete mineralization of CV into non-toxic byproducts. Furthermore, this review emphasizes the emerging role of Artificial Neural Networks (ANNs) as superior tools for optimizing degradation parameters, demonstrating higher predictive accuracy and scalability compared to traditional methods like Response Surface Methodology (RSM). Potential operational challenges and future directions—including machine learning-driven optimization, real-effluent testing potential, and the development of solar-active catalysts—are further discussed. This work not only consolidates recent breakthroughs in ZnO-based photocatalysis but also provides a forward-looking perspective on sustainable wastewater treatment strategies. Full article

Redox flow batteries (RFBs) are an emerging class of large-scale energy storage devices, yet the commercial benchmark—vanadium redox flow batteries (VRFBs)—is highly constrained by a modest open-circuit potential (1.26 V) while posing an expensive and volatile material procurement costs. This review focuses on recent progress in diversifying redox-active species to overcome these limits, highlighting chemistries that increase overall cell voltage, energy density, and efficiency while maintaining long cycle life and safety. The study dwells deeper into manganese-based systems (e.g., Mn/Ti, Mn/V, Mn/S, M/Zn) that leverage Mn’s high positive potential while addressing Mn(III) disproportionation reactions; iron-based hybrids (Fe/Cr, Fe/Zn, Fe/Pb, Fe/V, Fe/S, Fe/Cd) that exploit the low cost, and its abundance, along with membrane and electrolyte strategies to prevent the potential issue involving crossover; cerium-anchored catholytes (Ce/Pb, V/Ce, Eu/Ce, Ce/S, Ce/Zn) that deliver high operational voltage by implementing an acid-base media, along with selective zeolite membranes; and halide systems (Zn–I, Zn–Br, Sn–Br, polysulfide–bromine/iodide) that combine fast redox kinetics and high solubility with advances such as carbon-coated membranes, bromine complexation, and ambipolar electrolytes. Across these various families of RFBs, the review highlights the modifications made to the flow-fields, membranes, and electrodes by utilizing a zero-gap serpentine flow field, sulfonated poly(ether ether ketone) (SPEEK) membranes, carbon-modified and zeolite separators, electrolyte additives to enhance the voltage (VE%), and thereby energy (EE%) efficiency, while reducing the overall system cost. These modifications to the existing RFB technology offer a promising alternative to traditional approaches, paving the way for improved performance and widespread adoption of RFB technology in large-scale grid-based energy storage solutions. Full article

Cancer development in BRCA1 carriers is a multi-step process, which is triggered by several factors and mechanisms that are not clearly understood. Most BRCA1 carriers develop triple-negative breast cancer (TNBC)—estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2 -negative cancers—which originates from ER/PR/HER2-negative breast progenitor cells. Due to a lack of ER/PR/HER2-negative cell models with BRCA mutations, the processes inducing cancer development in BRCA carriers have not been comprehensively studied. Thus, studies characterizing ER/PR/HER2-negative cells carrying a BRCA1 germline mutation are needed to gain more in-depth knowledge about the steps leading to cancer initiation in BRCA1 carriers. To study the cancer development in these patients, we established a protocol for the generation of human ER/PR/HER2-negative breast organoids carrying a BRCA1 germline mutation. We confirmed that these organoids are unresponsive to estrogen, can self-renew, and express the stem/progenitor marker CD44. In addition, we observed that these organoids contain outgrowths that resemble the mature ductal and lobular units of the mammary gland, thus making it a suitable model system to study how cancer develops in ER/PR/HER2-negative mammary cells that carry a BRCA1 germline mutation. Full article

Background and Aim: People with HIV (PWH) have historically been excluded from cancer immunotherapy trials due to concerns over immune dysregulation and safety. This systematic review evaluates the safety, efficacy, and immunologic outcomes of Programmed death-1 (PD-1) inhibitors in PWH diagnosed with non-small-cell lung cancer (NSCLC). Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and Medline through January 2025. Studies were included if they reported outcomes of ICIs in PWH with NSCLC. Data extraction included progression-free survival (PFS), overall survival (OS), immune-related adverse events (irAEs), antitumor response, HIV viral control, and immunologic parameters. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. Results: Six cohort studies (n = 762 patients) met inclusion criteria. ICIs used included nivolumab, pembrolizumab, atezolizumab, and durvalumab, with treatment durations ranging from 3.1 to 5.4 months. Median PFS ranged from 3.0 to 6.3 months, and OS ranged from 10.0 to 66.0 months. Overall response rates (ORRs) varied from 13% to 75%, and disease control rates (DCRs) ranged from 47% to 62.5%. irAEs occurred in 25% to 75% of patients, with 6–20% experiencing grade 3–4 events. Corticosteroids were required in 13–29% of patients, and treatment discontinuation due to toxicity occurred in up to 30%. Most patients had controlled HIV, with CD4 counts typically above 300 cells/μL and undetectable viral loads. Conclusions: ICIs appear safe and effective in PWH with NSCLC, with toxicity and efficacy outcomes comparable to the general population. While immunotherapy should not be withheld based solely on HIV status, better standardization in reporting HIV-related variables is needed to optimize patient selection and management. Full article

Background: Ulcerative colitis (UC), a chronic and relapsing form of inflammatory bowel disease (IBD), arises from a multifactorial interplay of genetic predisposition, immune dysregulation, and environmental triggers. Despite advances in understanding UC pathogenesis, the identification of reliable biomarkers and key regulatory genes remains essential for unraveling disease mechanisms. Such insights are crucial for improving diagnostic precision and developing personalized therapeutic strategies. Methods: In this study, gene expression profiles from publicly available microarray and RNA-sequencing datasets were systematically analyzed using advanced bioinformatics tools. Differentially expressed genes (DEGs) were identified through statistical comparisons, and functional enrichment analyses were performed to explore their biological relevance. A total of 141 overlapping DEGs were extracted from three GEO datasets, and 20 key DEGs were further prioritized via protein–protein interaction (PPI) network construction. Hub genes, relevant signaling pathways, associated transcription factors (TFs), and microRNAs (miRNAs) linked to disease progression were identified. Potential therapeutic compounds were also predicted through computational drug–gene interaction analysis. Results: The analysis revealed a panel of novel biomarkers-TLR2, IFNG, CD163, CXCL9, CCL4, PRF1, TLR8, ARG1, LILRB2, FPR2, and PPARG-that function as key hub genes implicated in ulcerative colitis (UC) pathogenesis. These genes were associated with critical biological processes including signal transduction, inflammatory and immune responses, proteolysis, lipid transport, and cholesterol/triglyceride homeostasis. Furthermore, transcription factors (FOXC1, GABPA, GATA2, SUPT5H) and microRNAs (hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-24-3p, hsa-miR-23a-5p, hsa-miR-26a-5p) revealed key regulatory networks influencing post-transcriptional gene regulation. Molecular docking analysis predicted Apremilast and Golotimod as promising therapeutic candidates for UC intervention. Conclusions: In conclusion, this study enhances our understanding of ulcerative colitis pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies. Full article

The Inner Mongolia Cashmere goat (IMCG) industry is a major contributor to global cashmere production, with fleece traits serving as key economic indicators that directly impact both income and the long-term sustainability of the industry. When genome-wide SNPs are used to estimate kinship matrices, the traditional animal model implicitly assumes that all SNPs have the same effect-size distribution. However, in practice, there are differences in the genetic mechanisms and complexity of different traits. We conducted a genome-wide association study (GWAS) on 2299 IMCGs genotyped with 67,021 SNPs, which were obtained after imputation. The traits measured included cashmere yield (CY), wool length (WL), cashmere length (CL), and cashmere diameter (CD), with a total of 33,564 records collected. The top 5% to 20% of the significant SNPs from the GWAS were used as biological prior information. We then assigned proportional weights based on their contribution to the overall genetic variance and further integrated them with the remaining loci to construct a kinship relationship matrix for estimating genetic parameters and genomic breeding value. By incorporating prior marker information from the GWAS, it was found that the heritability estimates for CY, WL, CL, and CD were 0.26, 0.37, 0.09, and 0.35, respectively. For CY and CL, integrating the top 5% of prior SNP markers yielded the highest genomic prediction accuracies of 0.742 and 0.673, representing improvements of 16.67% and 19.75% over models that did not utilize prior information. In contrast, for WL and CD, the highest accuracies of 0.851 and 0.780 were achieved by integrating the top 10% of prior SNP markers, reflecting improvements of 9.81% and 10.14%, respectively. Compared with the conventional GBLUP method, this method of integrating GWAS-derived prior markers for genomic genetic evaluation can significantly improve the accuracy of genomic prediction for fleece traits in IMCGs. This approach facilitates accurate selection for fleece traits in IMCGs, enabling accelerated genetic progress through long-term breeding programs. Full article

Heavy metal (HM) contamination in agricultural soils poses a significant threat to soil health and plant productivity. This study investigates the impact of cadmium (Cd) and zinc (Zn) stress on tomato plants (Solanum lycopersicum) and explores the mitigation potential of microbial biostimulants (MBs), including arbuscular mycorrhizal fungi (AMF) and Pseudomonas fluorescens So_08 (PGPR), over a 52-day period using multi-omics approaches. Root exudate profiling revealed distinct metabolic changes under HM stress, which compromised soil–plant interactions. Cd stress reduced the secretion of phenylpropanoids (sum LogFC: −45.18), lipids (sum LogFC: −27.67), and isoprenoids (sum LogFC: −11−67), key metabolites in antioxidative defense, while also suppressing rhizosphere fungal populations. Conversely, Zn stress enhanced lipid exudation (such as sphingolipids and sterols, as sum LogFC of 8.72 and 9.99, respectively) to maintain membrane integrity and reshaped rhizobacterial communities. The MBs application mitigated HM-induced stress by enhancing specialized metabolite syntheses, including cinnamic acids, terpenoids, and flavonoids, which promoted crop resilience. MBs also reshaped microbial diversity, fostering beneficial species like Portibacter spp., Alkalitalea saponilacus under Cd stress, and stimulating rhizobacteria like Aggregatilinea spp. under Zn stress. Specifically, under Cd stress, bacterial diversity remained relatively stable, suggesting their resilience to Cd. However, fungal communities exhibited greater sensitivity, with a decline in diversity in Cd-treated soils and partial recovery when MBs were applied. Conversely, Zn stress caused decline in bacterial α-diversity, while fungal diversity was maintained, indicating that Zn acts as an ecological filter that suppresses sensitive bacterial taxa and favors Zn-tolerant fungal species. Multi-omics data integration combined with network analysis highlighted key features associated with improved nutrient availability and reduced HM toxicity under MB treatments, including metabolites and microbial taxa linked to sulfur cycling, nitrogen metabolism, and iron reduction pathways. These findings demonstrate that MBs can modulate plant metabolic responses and restore rhizosphere microbial communities under Cd and Zn stress, with PGPR showing broader metabolomic recovery effects and AMF influencing specific metabolite pathways. This study provides new insights into plant–microbe interactions in HM-contaminated environments, supporting the potential application of biostimulants for sustainable soil remediation and plant health improvement. Full article

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and is involved in cognitive functions and withdrawal. The cardiovascular effects of AG began to be explored after the hypotensive effect of clonidine, an imidazoline agonist, was demonstrated. The current study aimed to systematize the effects of AG on the cardiovascular system obtained in previous preclinical studies. Methods: We searched three databases, PubMed, Cochrane, and Embase, using the keywords “agmatine” and “cardiac” or “vascular.” Results: Sixty studies were eligible and included in the analysis. Initially identified as Clonidine Displacing Substance (CDS), AG has demonstrated dual effects—an increase or decrease in blood pressure or in heart rate. Conclusions: The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used. Full article

This study collected 820 topsoil samples from cultivated lands across Ningxia, covering the Yellow River irrigation area, the central arid zone, and the southern mountainous region. The ordinary kriging were spatially interpolated to analyze As, Hg, Cd, Cr, and Pb heavy-metal pollution spatial patterns. Pollution was evaluated using the Nemerow and geoaccumulation (I_(geo)) indices, and sources quantified via Pearson correlations, PCA (Principal Component Analysis), and PMF (Positive Matrix Factorization). The results indicated that Hg and Cd posed the highest ecological risks. The overall mean concentrations (mg.kg⁻¹) of Hg, Cd, As, Pb, and Cr were 0.04, 0.27, 9.91,23.81, and 57.34, respectively. Compared with the background values, they were 1.90, 2.41, 0.83, 1.14, 2.74 times higher, respectively. Geospatially, regions with higher pollution probabilities for Cd, Cr, Pb, Hg, and As were concentrated in the northern and central parts of Ningxia, whereas the southern region exhibited lower pollution probabilities. pH significantly influenced the accumulation and spatial distribution of heavy metals in soil. Source apportionment identified three primary contributors: transportation and natural parent materials (As, Pb, Cr), industrial activities (Hg), and agricultural practices (Cd). Hg and Cd were identified as the key risk elements requiring prioritized management. These results enhance understanding of the pollution levers of heavy metals in Ningxia cultivated soils, and also provide foundation for developing more scientific and precise soil risk control policies, offering significant practical value for environmental risk management. Full article

Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability. Full article

Reliable schedule-risk estimation in hybrid software development lifecycles is strategically important for organizations adopting AI in software engineering. This study addresses that need by transforming routine process telemetry (CI/CD, SAST, traceability) into explainable, quantitative predictions of completion time and rework. This paper introduces an integrated probabilistic model of the hybrid software development lifecycle that combines Generalized Evaluation and Review Technique (GERT) network semantics with I-AND synchronization, explicit artificial-intelligence (AI) interventions, and a fuzzy treatment of epistemic uncertainty. The model embeds two controllable AI nodes–an AI Requirements Assistant and AI-augmented static code analysis, directly into the process topology and applies an analytical reduction to a W-function to obtain iteration-time distributions and release-success probabilities without resorting solely to simulation. Epistemic uncertainty on critical arcs is represented by fuzzy intervals and propagated via Zadeh’s extension principle, while aleatory variability is captured through stochastic branching. Parameter calibration relies on process telemetry (requirements traceability, static-analysis signals, continuous integration/continuous delivery, CI/CD, and history). A validation case (“system design → UX prototyping → implementation → quality assurance → deployment”) demonstrates practical use: large samples of process trajectories are generated under identical initial conditions and fixed random seeds, and kernel density estimation with Silverman’s bandwidth is applied to normalized histograms of continuous outcomes. Results indicate earlier defect detection, fewer late rework loops, thinner right tails of global duration, and an approximately threefold reduction in the expected number of rework cycles when AI is enabled. The framework yields interpretable, scenario-ready metrics for tuning quality-gate policies and automation levels in Agile/DevOps settings. Full article