Search Results (998)

The literature collected from various search engines and high-quality scientific databases reveals that amino acid (AA)-functionalized nanoparticles have emerged as a promising field for selective detection and remediation of heavy metals (HMs). Among the various nanoparticles (NPs), gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have drawn considerable attention, attributed to their unique optical, catalytic, and surface plasmon resonance properties. Functionalization with amino acids significantly enhances nanoparticle stability, biocompatibility, and metal-binding affinity through diverse functional groups. AA-functionalized AuNPs, including glycine, cystine, leucine, methionine, tyrosine, aspartic acid, histidine, and lysine-capped systems, exhibit tunable selectivity toward heavy metal ions. Bifunctionalization strategies further enhance sensitivity by inducing nanoparticle aggregation or signal amplification. Beyond single amino acids, polypeptides and protein-functionalized AuNPs offer enhanced molecular recognition and multivalent binding, expanding their applicability in complex matrices. Similarly, amino acid-functionalized AgNPs, such as those capped with similar amino acids stated above, exhibit strong interactions with heavy metals, AA bifunctionalization, and bimetallic nanoparticles (BNPs), particularly amino acid-functionalized Au–Ag systems, which combine the advantages of both metals, leading to improved sensitivity, selectivity, and signal strength. Although these advances have been made, a major gap remains in the systematic comparison of different amino acids, peptides, and bimetallic systems under real-world conditions. This gap can be addressed by standardized testing methods, clearer structure–function relationships and combined experimentation to guide the rational design of more efficient AA-functionalized nanoparticles. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by therapeutic resistance and poor prognosis, underscoring the need for new therapeutic strategies. Bufalin, a major bioactive constituent of Venenum bufonis, has shown antitumor activity in several cancer types; however, its mechanism of action in PDAC remains incompletely defined. In this study, we investigated the antitumor effects of bufalin in PDAC using in vitro assays, mouse tumor models, and integrative transcriptomic, proteomic, metabolomic, and bioinformatic analyses. Bufalin inhibited PDAC cell viability, clonogenic growth, migration, and tumor progression in vivo. Pharmacological rescue experiments indicated that ferroptosis contributes importantly to bufalin-induced cytotoxicity, although apoptosis- and pyroptosis-related pathways may also be involved. Multi-omics analyses revealed coordinated alterations in calcium homeostasis, endoplasmic reticulum (ER) stress/unfolded protein response (UPR) signaling, and ferroptosis-related metabolic pathways. Further experiments showed that bufalin was associated with disrupted intracellular Ca²⁺ homeostasis, IP₃R-linked ER Ca²⁺ release, activation of PERK/eIF2α/ATF4 signaling, increased ATF3 expression, reduced SLC7A11 and GPX4 expression, glutathione depletion, and enhanced lipid peroxidation. Molecular docking and surface plasmon resonance assays supported an in vitro physical interaction between bufalin and IP₃R1/IP₃R3, while inhibition of ER stress attenuated several bufalin-induced ferroptosis-related phenotypes. Bioinformatic analyses further showed that higher ER stress and ferroptosis signature scores were associated with improved overall survival in PDAC, and concurrent activation of both signatures was linked to the most favorable prognosis. Collectively, these findings support that bufalin suppresses PDAC progression through coordinated ER stress- and ferroptosis-related responses, highlighting ER stress-ferroptosis crosstalk as a potential therapeutic vulnerability in PDAC. Full article

Biophysical sensing technologies have become central to modern drug discovery because they enable direct, quantitative characterization of ligand–target interactions. In contrast to conventional biochemical and cellular assays that infer binding from downstream functional responses, biophysical methods detect interaction events through measurable physical changes such as refractive index, heat, fluorescence, mass, or protein stability. This review surveys the major classes of biophysical sensors used in drug discovery, including surface-based optical methods, calorimetry, solution-state spectroscopic techniques, mass spectrometry-based approaches, and cellular target engagement assays. For each modality, we outline the measurement principle, the key parameters obtained, and its value across hit identification, hit validation, lead optimization, and mechanism-of-action studies. We also emphasize the growing importance of combining orthogonal methods to improve confidence in binding data, resolve assay artifacts, and strengthen early decision-making. Finally, we discuss how biophysical measurements are increasingly integrated with structural biology and computational analysis to support more predictive and mechanism-driven discovery workflows. Collectively, these technologies provide a richer and more reliable understanding of molecular recognition and thereby improve the progression of drug candidates. Full article

Biomaterials play a central role in tissue engineering and regeneration by providing scaffolds that support cell adhesion, proliferation and differentiation while modulating the surrounding microenvironment. They represent promising alternatives to traditional surgical approaches that may lead to complications or tissue damage, and their performance is influenced by chemical composition, mechanical behavior, architecture and interfacial properties, all of which can be precisely tuned through advanced fabrication and surface modification strategies. This review synthesizes evidence from a comprehensive literature search across major scientific databases, focusing on highly cited studies and available clinical data, and examines natural and synthetic biomaterials, their biological responses, functional characteristics, and surface modification methods. Emphasis is placed on Cold Atmospheric Plasma (CAP), which selectively modifies the outermost nanolayer of materials, enhancing hydrophilicity, functional group density, protein adsorption and overall cell–material interactions, as well as improving drug loading capacity. The review also considers stem cell interactions with biomaterials and emerging applications of artificial intelligence (AI) for predicting performance and guiding material optimization. Overall, the analysis highlights that natural matrices provide intrinsic bioactivity, synthetic polymers offer tunable mechanics and degradation profiles, and composite systems integrate these advantages. Advances in technologies such as electrospinning and 3D/4D printing enable precise control over architecture, supporting cell colonization and vascularization. Collectively, developments in CAP treatments and AI-driven design strategies are strengthening the regenerative potential of biomaterials and advancing their clinical translation. Full article

The plague, caused by Yersinia pestis, has resulted in significant mortality over the past century. Despite advances in antimicrobial therapy, plague remains a re-emerging infectious disease with ongoing outbreaks and increasing concerns regarding antimicrobial resistance. Today, plague cases are still being reported, and the loss of effectiveness of treatment methods remains a major challenge. Therefore, effective treatment strategies are needed. In this study, we aimed to develop aptamers specific to Yersinia outer protein M (YopM), a key immunosuppressive protein that is essential for virulence. Our goal was to develop an aptamer that binds to YopM and inhibits its interaction with the human DEAD-box helicase 3 (DDX3) protein. YopM-DDX3 protein interaction was targeted because of its key role in nucleocytoplasmic shuttling of YopM. To achieve this, we developed the YopM16 aptamer using magnetic bead-based (Systematic Evolution of Ligands by Exponential Enrichment) (SELEX). The selected YopM16 aptamer exhibited a half-maximal inhibitory concentration(IC₅₀) value of 103.3 ± 2 nM and effectively inhibited the interaction between YopM and DDX3. The inhibitory effect of the aptamer on protein interaction was confirmed using a pull-down assay and colorimetric test. Given that protein–protein interaction surfaces are considered undruggable, YopM16 is a promising inhibitor with the potential to serve as a molecular tool to investigate the virulence mechanism of YopM, as well as a novel antibacterial agent upon validation of its inhibition in cellular models. Full article

Acute lymphoblastic leukemia (ALL) is a genetically and epigenetically heterogeneous malignant disease characterized by different subtypes with varying sensitivities to conventional chemotherapy. Despite significant improvements in survival rates, relapse remains the primary cause of treatment failure, often associated with intrinsic or acquired drug resistance. First-line therapy at diagnosis represents a major determinant of relapse in ALL. In this study, we performed a transcriptome and drug response profiling analysis to identify subtype-specific cell surface proteins that are overexpressed in patients with poor response to induction therapy. We summarize the current state of knowledge regarding chemotherapy responses, resistance mechanisms to standard cytostatic drugs and the increasing importance of cell biomarkers as predictors of an adverse disease course and potential therapeutic targets. We discuss the results of clinical and molecular studies linking specific genomic alterations—such as KMT2A-rearrangements, Ph-like, DUX4-rearrangements and T-ALL—to drug resistance and highlight surface antigens like CSPG4, HER2, MCAM and ROR1 that define high-risk leukemia phenotypes. The integration of transcriptomic, immunophenotypic and drug response data could enable a new generation of risk-adapted, surface-directed strategies for relapse treatment in ALL. Our analysis therefore provides subtype-specific predictive therapeutic targets for relapse treatment in ALL. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article

With the rapid progression of global industrialization and urbanization, heavy metal contamination has emerged as a major global threat, especially cadmium pollution. Consequently, optimizing remediation measures has become a pivotal means to solve cadmium contamination. Compared to traditional physical and chemical remediation methods, microbial remediation has great potential in addressing cadmium pollution. In this study, a novel bacterial strain, Chryseobacterium sp. HGX-24, exhibiting high cadmium resistance was successfully isolated and screened from cadmium-contaminated environments. A preliminary discussion of the response mechanisms of this strain under cadmium stress is provided. Additionally, preliminarily explored the synergistic remediation of microbial-plant in cadmium-contaminated soil. Under conditions of high cadmium concentration, cadmium ions were effectively adsorbed by strain HGX-24 through extracellular polymers and functional groups on the cell wall surface, including −COOH, −CONH−, −NH, −OH, and >C=O. Extracellular proteins and polysaccharides were secreted by strain HGX-24 to regulate the adverse effects of heavy-metal cadmium ions on bacterial growth. Furthermore, the expression of genes such as antioxidant defense and ROS scavenging (katG, fabG, ybjT), Fe-S cluster assembly (sufB, sufD), sulfur metabolism (cysAU), amino acid metabolism (hisA, cysD, aspC), phenylacetic acid catabolism (paaC), and ribosomal proteins (rplC, rpsC, rpsL, rplA, rplY, rpmC) was regulated, affecting the synthesis and metabolism of membrane transporters (ABC transporters and efflux RND transporters), antioxidant enzymes (SOD, COT, POD), Fe-S clusters, thioredoxin family proteins, and ribosomal proteins, thereby enhancing resistance to cadmium toxicity. Moreover, strain HGX-24 was found to regulate the activities of redox enzymes in Zea mays L., thereby alleviating oxidative stress and reducing the negative feedback effects of reactive oxygen species in Z. mays. Full article

Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide, with current polysaccharide-based vaccines offering limited serotype coverage, high production costs, and reduced efficacy in vulnerable populations. These limitations have prompted the search for conserved pneumococcal proteins as universal vaccine candidates. Among them, pneumococcal surface protein A (PspA) stands out as a major virulence factor, present in virtually all clinically relevant strains, and capable of interfering with complement activation, opsonophagocytosis, and host defense mechanisms. Over three decades of research have demonstrated PspA’s strong immunogenicity, protective efficacy in multiple animal models, and safety in early-phase clinical trials. Here, we critically review advances in PspA-based vaccine development, including recombinant protein fragments, fusion constructs, nanoparticle formulations, and live-vector platforms. We highlight the structural and immunological determinants underlying its protective potential, while discussing major challenges such as antigenic variability and cross-reactivity across pneumococcal strains expressing distinct PspA clades. By integrating recent experimental and translational findings, this review outlines the opportunities and obstacles for the implementation of serotype-independent PspA-based vaccines. Full article

Fungal pathogens pose a major threat to global agriculture and human health, necessitating alternative antifungal strategies with high efficacy and low resistance potential. Antifungal proteins (AFPs) from filamentous fungi are promising candidates due to their stability, selectivity, and diverse mechanisms of action. Here, we characterize Beauveria brongniartii antifungal protein (BbroAFP), a novel cysteine-rich protein from the entomopathogenic fungus B. brongniartii, and investigate its antifungal activity against Botrytis cinerea. Recombinant BbroAFP was expressed in Pichia pastoris, purified, and verified by liquid chromatography–tandem mass spectroscopy (LC–MS/MS) and in silico modeling. BbroAFP showed potent antifungal activity with minimum inhibitory concentrations (MICs) as low as 1 µM against several phytopathogenic fungi, while exhibiting no significant antibacterial activity. Activity was maintained across a wide range of pH and temperature conditions. Confocal microscopy revealed rapid surface binding followed by cytosolic internalization without major cell wall disruption. BbroAFP induced a rapid, transient burst of reactive oxygen species (ROS), accompanied by nuclear DNA fragmentation. Gene expression analysis revealed a transient increase in aif1, whereas mca1 expression decreased at later time points and mca2 remained largely unchanged, suggesting a metacaspase-independent response. Detached tomato leaf assays showed effective protection against B. cinerea without detectable phytotoxicity. Cytotoxicity assays confirmed a favorable safety profile, supporting further evaluation of BbroAFP for plant protection. Full article

Bacterial persistence has been extensively studied as a possible explanation for strain survival under stress; however, in Enterococcus spp., this ability is still an understudied phenomenon. In this study, 40 Enterococcus spp. isolates of human clinical (n = 10), veterinary commensal (n = 10), veterinary clinical (n = 10) and veterinary environmental (hospital surfaces) (n = 10) origins, were exposed to a high concentration of ciprofloxacin. Time–kill curves were established, after which antimicrobial susceptibility profiles were reassessed. Subsequently, the only presumptive persister was selected for Whole-Genome Sequencing, together with one isolate showing no evidence of persister formation. Comparative genomic analyses were conducted to identify genetic variations between exposed and non-exposed isolates and to explore potential genetic determinants associated with persistence. Observed genetic features present in the persister isolate included toxin–antitoxin systems, a cold-shock protein and the tyrosine-type recombinase/integrase XerC, which may represent putative candidates for further investigation. Interestingly, the majority of toxin–antitoxin system-associated genes were found in plasmids. This study represents an important step towards a better understanding of persistence development in Enterococcus spp.; however, validation using other methodologies such as RNA-sequencing is an important next step. Full article

Glycosylation is one of the most prevalent post-translational modifications of membrane proteins and plays a central role in regulating their structure and function. Unlike many existing reviews that address glycosylation in a system-wide context, this review focuses specifically on membrane proteins and examines how glycosylation shapes their functional behavior and clinical relevance. Because membrane proteins are exposed to the extracellular environment, glycans on their surface directly influence protein folding, receptor organization, and interactions with ligands and immune components. These diverse effects can be understood within a common mechanistic framework in which glycosylation modulates protein conformation, receptor clustering, and membrane organization, thereby altering signaling, adhesion, transport, and immune recognition. We discuss how N-linked and O-linked glycosylation regulate major classes of membrane proteins across these processes. Particular attention is given to disease-associated alterations in glycosylation, especially in cancer, immune and inflammatory disorders, and metabolic disease. For instance, glycosylation-dependent stabilization of PD-L1 and modulation of receptor signaling, such as EGFR, illustrate how glycan modifications contribute to immune evasion and therapeutic response. We further consider the clinical implications of membrane protein glycosylation, including its roles in biomarker development and as a potential target for therapeutic intervention. Advances in glycoproteomic technologies have enabled increasingly detailed characterization of site-specific glycosylation, although significant analytical challenges remain, particularly for membrane proteins. Overall, this review highlights membrane protein glycosylation as a dynamic regulatory layer that links molecular mechanisms to functional outcomes and clinical applications. Full article

S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution characteristics, sequence diversity, domain composition and antigenic epitope distribution. The results showed that the HP0197 gene, which has a detection rate of 91.72%, can be divided into seven major phylogroups (I–VII) and the following two structural types: short form (HP0197-S) and long form (HP0197-L). All sequences contained signal peptides, transmembrane structures, LPXTG anchoring motifs, as well as conserved GAGBD and G5 domains, among which tandem repeats of the G5 domain existed in the long HP0197-L type. Tertiary structure prediction indicated that HP0197 has a spatial architecture of “conserved at both ends and flexible in the middle”, in which B-cell epitopes are mainly enriched near the GAGBD and G5 domains, suggesting these regions are the key targets for inducing cross-immune protection. It systematically elucidates the diversity and structural characteristics of the HP0197 protein from the perspective of population genetics, which provides a theoretical basis for optimizing existing subunit vaccines, designing broad-spectrum multi-epitope vaccines and exploring novel anti-infection strategies. Full article

Low temperature during grain filling is a major constraint affecting rice quality in cold regions. This study investigated how low temperature influences rice quality and starch characteristics at different periods of the grain-filling stage using two Japonica rice cultivars, Kenjing 7 (KJ7, moderate stress tolerance) and Kenjing 8 (KJ8, strong stress tolerance). Low-temperature treatments (17/13 °C, day/night) were applied during the early (5–11 days after anthesis), middle (12–18 days), and late (19–25 days) grain-filling stages and milling, appearance, nutritional, eating and cooking qualities as well as starch physicochemical properties were evaluated. Responses differed markedly between cultivars and treatment periods. Under low-temperature conditions, brown rice and milled rice rates of KJ8 increased during the early and middle grain-filling stages, whereas those of KJ7 declined during the late stage. Low-temperature stress increased protein, total starch, and amylose contents, while reducing gel consistency and the taste value of KJ7. Grain chalkiness increased significantly during the late stage, whereas during the early and middle stages, grain chalkiness, peak viscosity, and breakdown decreased and setback increased. Low temperature increased starch granule size and the proportions of short and intermediate chains of amylopectin, reduced medium-long and long chain and relative crystallinity, without altering starch crystalline type, and produced uneven starch particle surfaces with small pores. These effects were most pronounced during the late grain-filling stage. Overall, low temperature altered starch content and structure, thereby modifying pasting properties and ultimately leading to differences in rice quality. Full article

Nanomedicine has advanced rapidly as engineered nanoparticles have become increasingly capable of improving drug stability, targeting, controlled release, and biocompatibility. However, nanoparticle clinical utility relies on both delivery efficiency and how they are metabolized, retained, and cleared. This review examines the major biological pathways governing nanoparticle clearance and discusses how engineering parameters can be tuned to influence bioaccumulation, metabolism, excretion, and therapeutic performance with a wide range of available materials. This article is a narrative review of the recent and foundational literature on medically relevant nanoparticles, including lipid-based, polymeric, biopolymer, inorganic, polylactide, and bile-derived systems. All relevant translational, biochemical, chemical, and clinical literature from PubMed was searched from January 1971 to January 2026 to obtain a representative sample of work before information extraction. Nanoparticle clearance is governed by interconnected molecular and organ-level processes that vary according to composition, size, surface chemistry, and route of administration. Surface modifications with PEGylation, zwitterionic coatings, cholesterol, proteins, or responsive linkers can prolong circulation, alter immune recognition, and direct organ-specific handling. While rapid clearance remains desirable for many systemically acting drugs, prolonged intracellular or intratumoral retention may improve outcomes, particularly in boron neutron capture therapy and other activation-dependent treatments. Nanoparticle clearance should be regarded as a context-dependent design parameter rather than a universal limitation. Rational control of clearance kinetics may improve both safety and therapeutic effectiveness in next-generation engineered drug delivery systems. Full article