Search Results (31,516)

The discovery of novel anti-infective agents is a continuous challenge in medicinal chemistry, particularly due to the rise in resistant fungal and viral strains. Within this context, the biphenyl subunit has been identified as a highly versatile privileged structure capable of interacting with diverse protein targets via hydrophobic and π-interactions. The purpose of this study is to review the pharmacological potential of biphenyl-based compounds, focusing on their application as anti-infective agents. We comprehensively analyzed recent literature and rational design strategies concerning biphenyl derivatives, examining structure-activity relationships, molecular docking insights, and structural optimizations aimed at enhancing both pharmacodynamics and pharmacokinetics. The reviewed studies demonstrate that incorporating biphenyl moieties yields compounds with potent antifungal and antiviral activities. Specifically, optimized biphenyl derivatives exhibit strong inhibitory effects against resistant Candida strains and crucial viral targets, including mutant variants of the HIV-1 reverse transcriptase and protease enzymes. Furthermore, strategic modifications, such as scaffold hopping and the introduction of specific substituents, successfully mitigated cytotoxicity and improved metabolic stability against cytochrome P450 enzymes. Biphenyl serves as a robust and adaptable scaffold for drug design. Its rational structural optimization provides a viable pathway to overcome drug resistance and develop effective, metabolically stable anti-infective therapeutics. Full article

This study investigates the antioxidant, enzyme inhibitory, and antimicrobial activities of water (WEHL) and ethanol (EEHL) extracts of hop (Humulus lupulus) cones. Phytochemical analyses revealed higher total phenolic content in EEHL (271.52 ± 0.13 mg GAE/g) than in WEHL (251.84 ± 0.06 mg GAE/g), as well as higher total flavonoid content (182.56 ± 0.45 mg QE/g for EEHL versus 179.39 ± 0.46 mg QE/g for WEHL). Antioxidant activity, determined by DPPH and ABTS assays, showed that EEHL had stronger radical scavenging capacity with IC₅₀ values of 19.13 ± 4.66 μg/mL (DPPH) and 12.66 ± 1.94 μg/mL (ABTS), compared to WEHL (DPPH: 20.90 ± 2.39 μg/mL; ABTS: 32.41 ± 4.29 μg/mL). In reducing assays, EEHL also showed better absorbance values in FRAP (0.77 ± 0.01), CUPRAC (2.09 ± 0.05), and Fe³⁺ reducing (1.95 ± 0.01) tests. EEHL likely outperformed WEHL due to solvent polarity and extraction efficiency. Moderately polar ethanol extracts a broader range of phenolics and flavonoids, including fewer polar bioactive compounds that contribute to antioxidant capacity and enzyme inhibition. This matches higher TPC/TFC in EEHL and explains stronger radical scavenging, reducing power, and multi-enzyme inhibition. Enzyme inhibition studies revealed that EEHL inhibited acetylcholinesterase (IC₅₀: 26.06 μg/mL), butyrylcholinesterase (IC₅₀: 44.00 μg/mL), α-glycosidase (IC₅₀: 119.31 μg/mL), and carbonic anhydrase isoenzymes hCA I (IC₅₀: 59.78 μg/mL) and hCA II (IC₅₀: 21.19 μg/mL). LC–MS/MS analysis identified major phenolic compounds such as isoquercitrin (3.14 ng/mL), rutin (0.60 ng/mL), and hesperidin (0.43 ng/mL) in EEHL. Antimicrobial screening showed selective activity against Staphylococcus aureus with an inhibition zone of 18.50 ± 0.58 mm, while no inhibition was observed against Escherichia coli and Candida albicans. These findings provide a solvent-dependent in vitro profile that can guide extraction strategies, support antioxidant and multi-enzyme screening (including hCA I and II), and identify candidates for selective antimicrobial evaluation and further preclinical investigation. Despite extensive use of hop extracts, comparative solvent-dependent profiling that links LC–MS/MS phenolic composition with a broad multi-enzyme inhibition panel, including the less frequently evaluated hCA I/II isoenzymes, remains limited. Therefore, the objective of this study was to systematically compare WEHL and EEHL in terms of phytochemical content and in vitro antioxidant, enzyme inhibitory, and antimicrobial activities. Overall, these results provide a solvent-dependent, comparative in vitro profile of WEHL vs. EEHL that can support antioxidant, multi-enzyme screening (including hCA I and II), and selective antimicrobial assays. Full article

The integration of appropriate tillage practices with straw returning can effectively mitigate soil degradation in Northeast China. However, limited research has explored the impacts of different tillage practices combined with varying straw incorporation depths on the structure and diversity of soil microbial communities. In 2016, a field experiment was initiated using a two-factor split-plot design, featuring six treatments: two tillage depths of 10 cm (D10) and 30 cm (D30) combined with three straw management practices—straw mixing incorporation (SM), straw deep burial (SB), and straw removal (SR). Soil samples collected in 2019 were analyzed for multiple soil properties and microbial indices. Results indicated that both straw returning and tillage depth significantly influenced soil organic carbon (SOC), soil total nitrogen (STN), total phosphorus (TP), and total potassium (TK), with the D30 treatment combined with straw returning optimizing soil nutrient contents most effectively. Under straw returning, D10 significantly increased urease activity in the 0–10 cm soil layer, whereas D30 enhanced this enzyme activity in the 10–30 cm soil layer, while β-glucosidase activity was less responsive to tillage depth. For the D10 treatment with straw returning, acid phosphatase activity was markedly higher than that in the straw removal treatment, whereas N-acetyl-β-D-glucosaminidase activity exhibited the opposite trend. Straw-returning methods had no significant effects on the bacterial and fungal Chao1 indices, while the Shannon index was positively correlated with key soil properties. Redundancy analysis (RDA) of microbial community composition at the phylum level and soil environmental factors revealed that soil nutrients in the 0–10 cm soil layer were positively correlated with Actinobacteriota, Ascomycota, and Basidiomycota, whereas the explanatory power of soil nutrients for microbial community variation decreased in the 10–30 cm soil layer. Our results highlight that tillage depth and straw returning can regulate soil microbial community composition and enhance soil nutrient cycling, thereby providing a theoretical basis for optimizing the combined application mode of tillage and straw-returning practices in Northeast China. Full article

Cymbidium goeringii, an important orchid species, holds significant aesthetic and commercial potential in horticulture. However, stem rot caused by Fusarium oxysporum has emerged as a major biological constraint hindering industry development. In this study, we isolated five endophytic fungal strains from C. goeringii roots—namely, DG3 (Bjerkandera), DG4 (Cylindrocarpon), CLG3 (Talaromyces), CLG6 (Clonostachys), and Z3 (Trichoderma)—and assessed their inhibitory efficacy against stem rot and their potential to promote growth in C. goeringii. In vitro assays indicated that all five fungal strains had the ability to fix nitrogen and produce indole-3-acetic acid, as well as the capability to produce protease and exert broad-spectrum antimicrobial effects. The five endophytic fungal strains exhibited stem rot-resistant effects, among which strain Z3 showed the best inhibitory effect against stem rot, with a control efficacy reaching 68.89%. Treatment of C. goeringii seedlings with these endophytic fungal fermentation broths for 100 d significantly promoted growth compared to the control. The fresh weight increased by 10.53% to 88.16%, and root activity was enhanced by 50% to 162.5%. Additionally, the plant height and the longest leaf length increased by up to 23.68% and 47.50%, respectively, compared to the control. Additionally, the total chlorophyll content was up to 25.34% higher than that of the control group, and the soluble protein content was up to 39.54% higher. The MDA content was reduced by up to 40.23% compared to the control group. These endophytes also regulated the activity of defense-related enzymes in C. goeringii, including delaying the decline in the activities of antioxidant enzymes such as superoxide dismutase, peroxidase, and catalase. These results highlight the potential of these five endophytic fungi as effective agents for managing stem rot in C. goeringii. Full article

Background/Objectives: Enteropathogenic Escherichia coli O157:H7 infection disrupts intestinal homeostasis, causing dysbiosis, barrier dysfunction, and inflammation. This study aimed to evaluate the protective efficacy and mechanisms of a novel probiotic, Bacteroides thetaiotaomicron type strain ATCC 29148, isolated from goat feces, against E. coli O157:H7-induced colitis. Methods: This study assessed the protective potential of the probiotic strain Bacteroides thetaiotaomicronBT6 and BT7 in vitro for GI tolerance, adhesion, and no adverse effects were observed. For the in vivo experiment, male C57BL/6J mice were divided into groups treated with Bacteroides thetaiotaomicron (BT6), PBS, E. coli O157:H7, or a combination. We employed integrated analyses including 16S rRNA gene sequencing, antioxidant status, cytokine profiling, and short-chain fatty acid (SCFA) measurement. Results: In vitro, Bacteroides thetaiotaomicron (BT6 and BT7) showed high gastrointestinal tolerance (71.89–93.22% survival). In vivo, it significantly mitigated infection-associated weight loss and disease activity (p < 0.05). Probiotic treatment enhanced barrier integrity, reduced colonic inflammation, and modulated systemic immune responses, notably increasing anti-inflammatory IL-10 while decreasing pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 (p < 0.05). It also alleviated oxidative stress by reducing malondialdehyde (MDA) and elevating antioxidant enzymes (SOD, CAT, GSH) and ATP. Fecal SCFA profiling revealed increased propionic and butyric acid. 16S sequencing indicated that B. thetaiotaomicron (BT6) administration increased beneficial families (Lactobacillaceae, Muribaculaceae) and suppressed pathobionts. Conclusions: B. thetaiotaomicron (BT6) probiotic with potential for mitigating enteropathogenic infection, an effect mainly determined by its capacity to reestablish the intestinal epithelial barrier and enhance global host health, and modulating the inflammatory response Full article

Bovine viral diarrhea virus (BVDV), a globally persistent pathogen, causes bovine viral diarrhea-mucosal disease (BVD-MD), a contagious bovine disease posing significant pressures on both public health and economic development. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits broad antiviral activities but suffers from poor aqueous solubility and low bioavailability, limiting its therapeutic potential against BVDV. To address this limitation, we developed BA-loaded poly (ethylene gly-col)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (BA-PEG-PLGA NPs). While autophagy and NLRP3 inflammasome activation have been individually implicated in viral pathogenesis, their functional crosstalk during BVDV infection remains uncharacterized. Herein, we evaluated the antiviral efficacy of BA-PEG-PLGA NPs through integrated in vitro and in vivo experiments. We employed quantitative polymerase chain reaction (qPCR), transcriptome sequencing, Western blot analysis, immunofluorescence microscopy, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms by which BA and BA-PEG-PLGA NPs combat bovine viral diarrhea virus (BVDV) infection. We found that both free BA and BA-PEG-PLGA NPs effectively attenuated BVDV replication in vitro and in vivo; notably, the nano-formulation exhibited superior efficacy. Mechanistically, BA and its nano-formulation restored autophagy homeostasis, suppressed ROS overproduction, and blocked NLRP3 inflammasome activation and pyroptotic cell death effects comparable to the specific NLRP3 inhibitor MCC950. These findings establish the autophagy–NLRP3/pyroptosis axis as a critical pathogenic mechanism in BVDV infection and reveal that nano-formulated baicalin represents an antiviral strategy by coordinately targeting this axis. This work not only provides a translatable nanomedicine approach for BVDV control but also expands the mechanistic understanding of flavonoid-based interventions in viral inflammatory diseases. Full article

Caffeic acid (CaA) and chicoric acid (ChA) each exhibit significant antioxidant activity when used alone, yet their combined effects on antioxidant capacity and intestinal health in zebrafish remain unclear. This study used isobolographic analysis to identify a 1:1 ratio of CaA to ChA as optimal for synergistic antioxidant activity, with its ABTS and DPPH IC₅₀ (21.65 μg/mL, 69.66 μg/mL) outperforming single monomers in vitro. In an oxazolone (Oxa)-induced zebrafish intestinal oxidative stress model, the CaA and ChA (CaA–ChA) mixture exerted antioxidant effects by upregulating the mRNA expression levels of HTR2A, Akt, Nrf2, and downstream antioxidant enzyme genes including SOD, CAT, and GPx in the zebrafish intestine, while downregulating Keap1 mRNA expression. Intestinal microbiota analysis revealed that the CaA–ChA mixture could positively regulate the intestinal microecological structure, characterized by targeted enrichment of the beneficial bacterium Cetobacterium and inhibition of the proliferation of potential pathogenic bacteria, including Bosea and Mycobacterium. Correlation analysis confirmed that the abundances of these key genera were closely associated with the expression of signaling pathway markers, suggesting that the microbiota–signaling pathway crosstalk was involved in the regulation of antioxidant processes. In conclusion, the CaA–ChA mixture (1:1) exerts a protective effect against intestinal oxidative stress, with the potential involvement of dual gut microbiota modulation and the HTR2A/Akt/Nrf2/Keap1 pathway. These findings provide experimental and theoretical support for the combined antioxidative application of CaA and ChA. Full article

Background and Clinical Significance: Mucopolysaccharidosis type VI is a rare lysosomal storage disorder due to arylsulfatase B enzyme deficiency, leading to progressive multisystem disease and complex airway. Acute respiratory infections can precipitate airway embarrassment. A structured treatment guideline is currently lacking. We present a 7-year-old MPS VI male with respiratory distress, highlighting the challenges in management. Case Presentation: Case review focusing on clinical presentation, imaging findings, and multidisciplinary decision-making during acute deterioration. A child diagnosed with MPS VI at the age of 3.5 years old, due to low arylsulfatase B enzyme activity and homozygous for c.275C>A p.(Thr92Lys) variant in the ARSB gene. At 7 years of age, he showed the signs of dyspnoea, increased respiratory effort with bilateral crepitations, and noisy breathing. Initial management included facemask oxygen, nebulised adrenaline, corticosteroids, and bronchodilators. Computer tomography scan of the neck and chest showed a complex upper airway, multiple tracheal narrowing, tortuosity, and an extra loop of truncus brachiocephalicus from the arch of the aorta. Potential interventions carried substantial risks due to abnormal airway and multisystem disease. Following extensive multidisciplinary discussion after careful consideration of the significant risks associated with invasive airway interventions, a shared decision was reached with the family to adopt a comfort-focused palliative care approach. Despite the best supportive care, the child unfortunately passed away after 3 months. The family was involved in every decision process and was fully supported. Conclusions: MPS VI is associated with complex airways and multisystem disease. Multidisciplinary decision-making with family is critical to safe and appropriate care. The rarity of the disease, lack of guidelines, complex airways, and multiple comorbidities make management challenging. Full article

This study evaluated activities of crude extracts from different parts of the tree of heaven (Ailanthus altissima (Mill.) Swingle) collected in Slovenia and Hungary, using effect-directed analyses based on hyphenation of high-performance thin-layer chromatography (HPTLC) and nine in vitro assays performed in situ on chromatographic plates after the separation. HPTLC separation combined with a set of four antibacterial assays, two antifungal assays, and three enzyme inhibitor assays to evaluate the extracts of 14 plant parts: young shoots, young leaves, mature leaves, yellow leaves, petioles of leaves, petioles of male inflorescences, petioles of fruits, female inflorescences, male inflorescences, mature male inflorescences, bark of 1–2-year branches, bark of 2-year branches, bark of tree trunk, and bark of roots. Antibacterial activities against Gram-positive bacteria (Bacillus subtilis, Rhodococcus fascians) and Gram-negative bacteria (Aliivibrio fischeri, Pseudomonas syringae pv. maculicola (Psm)), as well as inhibition of enzymes α-glucosidase, lipase, and acetylcholinesterase, were observed for all extracts. Extracts differed in their antifungal activities. Extracts of young shoots, mature leaves, petioles of leaves, and bark of roots showed antifungal activity against plant pathogens Fusarium avenaceum and Bipolaris sorokiniana. Extracts of yellow leaves, male inflorescences, bark of 1–2-year branches, and bark of tree trunks were only active against F. avenaceum, whereas extracts of young leaves were only active against B. sorokiniana. This study is the first to report that A. altissima extracts exhibit (1) antifungal activity against F. avenaceum and B. sorokiniana; (2) antibacterial activity against A. fischeri, Psm, R. fascians, and B. subtilis (except leaves, bark of branches and bark of tree trunks); and (3) inhibitory activity toward lipase, α-glucosidase (except bark of tree trunks), and acetylcholinesterase (except bark of tree trunks). Full article

Background/Objectives: Worldwide, diabetes is a 21st century disease with continuously increasing prevalence. Current medications often have long-term adverse effects, which is why new substances are needed to help combat these disadvantages. Methods: In this respect, the present study develops a series of compounds with potential antidiabetic activity, including synthesis, physicochemical–spectral characterization and in vitro–in silico evaluation. Results: The sulfonamide derivatives were obtained by condensation reactions of para-toluenesulfonamide (p-TSA) with two different isocyanates, directly or after the condensation reaction with urea. The spectroscopic methods, IR, ¹H-NMR, ¹³C-NMR, were used for the structural elucidation of the compounds to confirm the presence of the functional groups responsible for the antihyperglycemic action, namely amide, azomethine and sulfonyl groups. Cytotoxicity screening on NCTC fibroblasts confirmed the excellent safety profile of the most synthesized derivatives across the tested range (100–1500 μg/mL). In contrast, the p-TSA-c-d derivative showed a clear transition from a biocompatible profile at 100 μg/mL to a more cytotoxic phenotype at concentrations exceeding 750–1500 μg/mL. The synthesized derivatives, particularly p-TSA-c-d, exhibited remarkable antidiabetic potential by effectively inhibiting α-amylase and α-glucosidase, with IC₅₀ values as low as 46.54 μM, outperforming the standard reference acarbose. The molecular docking tests revealed different mechanisms for the inhibitory activity exerted by the p-TSA derivatives on the two targeted enzymes. Conclusions: Although these developed compounds can be considered promising antidiabetic agents, studies can be further deepened in the future by performing in vivo tests. Full article

The rhizosphere is a critical interface linking plants and soil; however, the mechanisms by which parasitic plants affect host growth through rhizosphere microecological changes remain unclear. This study systematically elucidates how Monochasma savatieri, a hemiparasitic plant, promotes blueberry growth by reshaping rhizosphere microecology. Pot experiments showed that parasitism significantly enhanced urease, sucrase, and soil nitrate reductase activities, improving organic matter decomposition and nutrient transformation efficiency. Concurrently, soil total nitrogen (TN), total phosphorus (TP), and total potassium (TK), along with alkali-hydrolyzable nitrogen (AN) and available potassium (AK), decreased, suggesting enhanced nutrient absorption by roots. At the microbial level, parasitism altered community composition and diversity, enriching functional taxa such as Nitrosomonas, OLB5, and Serendipita. Functionally, pathways related to stress resistance (necroptosis and glutamatergic synapses) were activated, whereas those linked to pathogen colonization (Pseudomonas aeruginosa biofilm formation and tryptophan metabolism) were suppressed. These modifications reduced harmful microbial competition, optimized nutrient cycling and signaling networks, and established a favorable rhizosphere microenvironment for root health. By integrating soil enzyme activity, nutrient dynamics, and microbial functions, M. savatieri systemically improves the rhizosphere microenvironment, ultimately enhancing blueberry growth. This study provides theoretical support for intercropping and management of parasitic plants with blueberries. Full article

Glyphosate is a widely used herbicide with increasing concern regarding its non-target impacts in coastal ecosystems and mariculture species. Here, we profiled acute physiological stress signatures of waterborne glyphosate exposure in the sea cucumber Apostichopus japonicus, integrating measured exposure concentrations, tissue residues, digestive and oxidative/innate immune biomarkers, and gut microbiota. After 24 h exposure, measured waterborne glyphosate confirmed the intended gradient (0.09 ± 0.02, 1.26 ± 0.09, and 4.49 ± 1.12 mg/L for low-, medium-, and high-dose treatments, respectively), and overt stress phenotypes with mortality occurred only at the high dose (36.67%), enabling separation of high-dose survivors (HS) and high-dose dead (HD) for downstream analyses. Tissue measurements showed low/background levels in controls, with compartment-specific distribution: the respiratory tree exhibited higher burdens at the medium dose, whereas coelomic fluid showed the highest burdens in HS at the 24 h endpoint. Functionally, most intestinal digestive enzymes were unchanged, but trypsin activity was consistently suppressed across exposed groups (p < 0.05). In coelomic fluid, oxidative stress responses were evident, with elevated MDA (L and M), reduced CAT (L, M, and HS), and reduced GSH-PX in HS (all p < 0.05), while SOD, GR, and lysozyme showed no significant changes. Gene sequencing of 16S rRNA (n = 3 per group) revealed significant shifts in community diversity/evenness (Shannon p = 0.0497; Simpson p = 0.0484) and beta diversity (PCo1 = 30.08%, PCo2 = 26.30%; PERMANOVA F = 1.816, p = 0.008), with LEfSe indicating discriminative taxa associated with exposure/outcomes. Collectively, these multi-level endpoints define an acute glyphosate stress signature in A. japonicus, linking internal dose distribution to oxidative disruption, impaired intestinal proteolysis, and microbiome restructuring. Full article

Soil salinization has become a major global constraint threatening ecosystem stability and agricultural production. As a prominent salt-tolerant turfgrass, Paspalum vaginatum (seashore paspalum) serves as an excellent material for exploring salt tolerance mechanisms. In this study, PvHAK12, a high-affinity K⁺ transporter (HAK) family gene isolated from seashore paspalum, was functionally characterized. PvHAK12 encodes a 788 amino acid protein with 13 transmembrane domains, belonging to the plasma membrane-localized ion transporters. It exhibits high sequence conservation with other HAK transporters and is predominantly expressed in roots and stems, with distinct tissue- and time-specific induction under salt stress. Yeast complementation assays revealed that PvHAK12 has no obvious K⁺ transport capacity but may mediate Na⁺ transport. Overexpression of PvHAK12 in Arabidopsis thaliana significantly reduced salt tolerance at germination, seedling and rosette stages, as reflected by lower germination rate, fresh weight, survival rate, the maximum quantum yield of photosystem II (Fv/Fm) value and chlorophyll content, accompanied by higher ion leakage. Under salt stress, transgenic plants accumulated more Na⁺ and less K⁺, leading to an elevated Na⁺/K⁺ ratio. Moreover, transgenic lines displayed weaker antioxidant enzyme activities and higher reactive oxygen species (ROS) accumulation. Transcript analysis further demonstrated that PvHAK12 overexpression suppressed the induction of multiple ion-transport and stress-responsive genes under salt conditions. These results indicate that PvHAK12 negatively regulates plant salt tolerance by disrupting ion homeostasis, antioxidant capacity and stress-related gene expression. Full article

As a global environmental problem, biological invasion poses a serious threat to natural ecosystems. To explore the influence mechanism of Alternanthera philoxeroides (Mart.) Griseb on the growth and development of landscape plants, this study systematically analyzed the effects of extracts from different organs (stems, leaves, and roots) of A. philoxeroides on the seed germination and seedling growth of Zinnia elegans Jacq. by combining the Petri dish filter paper method with a pot experiment to reveal the potential mechanism of allelopathy. The results showed that the aqueous extract of A. philoxeroides inhibited the seed germination and seedling growth of Z. elegans. The high concentration (100 mg·mL⁻¹) of stem and leaf extracts significantly reduced the germination rate (by 99.10% and 90.65%) and seedling morphological parameters. The allelopathic inhibition increased with an increase in concentration, and the inhibitory effect of stem and leaf extracts was significantly stronger than that of root extracts. Aqueous extracts from the roots, stems, and leaves of A. philoxeroides at three concentrations (25, 50, and 100 mg·mL⁻¹) induced oxidative stress in seedlings, as evidenced by the elevated malondialdehyde (MDA) content and dysregulated activities of antioxidant enzymes. Specifically, superoxide dismutase (SOD) and catalase (CAT) activities exhibited a concentration-dependent trend of initial induction followed by subsequent inhibition, while root activity was significantly suppressed (p < 0.05), ultimately impairing seedling growth. The aqueous extracts of A. philoxeroides showed a concentration-dependent inhibitory effect on the seed germination and seedling growth of Z. elegans. High concentrations of stem and leaf extracts exerted a significant inhibitory effect on seedling growth, and this growth suppression was attributed to the induction of oxidative stress by the extracts. This study elucidated the phytotoxicity degree and physiological response mechanisms underlying the biochemical allelopathy of A. philoxeroides on Z. elegans. The findings provide a theoretical foundation for the selection of horticultural plant cultivars resistant to allelopathic stress and the development of management strategies for invasive plants. Full article

Carbon dots offer excellent physico-chemical properties and biocompatibility for cancer theranostics systems, either as therapeutic agents themselves, or as potential drug carriers. It is, however, postulated that the drug carrier affects the mechanism of action and intracellular target molecules of a drug. Therefore, in the present study, we systematically evaluated protein alterations in HeLa cervical cancer cells after treatment with sulfur-doped carbon dots (S-CDs). Synchrotron Radiation μFTIR spectroscopy and label-free LC–MS/MS proteomics integrated with bioinformatics were used to assess molecular changes. μFTIR revealed a shift and increased intensity of α-helices, indicating structural changes in proteins as a result of the interaction between S-CDs and cells. Proteomic analysis identified 122 statistically significant (p ≤ 0.05) proteins with increased abundance and 61 with decreased abundance following S-CD exposure, many of which possess high α-helix content, consistent with μFTIR findings. Functional analyses showed that up-regulated proteins were enriched in molecular adaptor, transporter, and transcription regulator activities, particularly those involved in RNA metabolism and translation. Down-regulated proteins were dominated by protein-modifying enzymes and cytoskeletal components. Pathway enrichment analysis indicated alterations in mRNA processing, ribosomal pathways, translation factors, aminoacyl-tRNA biosynthesis, and proteasome degradation. Key hub proteins included ribosomal proteins and translation initiation factors. S-CD treatment led to opposite regulation of many proteins compared to their regulation in untreated HeLa cells including down-regulation of ribosomal proteins (RPS27L, RPS19, and RPS5), aminoacyl-tRNA biosynthesis proteins (IARS1, LARS1, and MARS1), and proteasome degradation proteins (PSMD2, PSMD3, and PSMD11), which aligns with the observed cytotoxic effect of S-CDs on cervical cancer cells. Overall, these results highlight significant proteomic and structural protein changes induced by S-CDs and support their potential for cervical cancer treatment, warranting further investigation of this nanomaterial’s biological applications. Full article