The efficient management of infected skin wounds is severely limited by the thick bacterial biofilm within the lesion, the intractable stratum corneum barrier of the perilesional skin, and the high toxicities of potent antibiotics. Sparfloxacin (SPFX) was withdrawn from the market due to its severe systemic side effects and UV-induced phototoxicity, while its severe hydrophobicity causes localized crystalline cytotoxicity upon topical application. To safely rejuvenate this potent drug, an integrated transdermal system combining photoshielding, SPFX-loaded solid lipid nanoparticles (SPFX-SLNs) with dissolving microneedles (MNs) was developed. This study primarily focuses on the systematic screening, formulation development, and optimization of SPFX-SLNs via Box-Behnken Design-Response Surface Methodology (BBD-RSM). The optimized nanocarriers exhibited a uniform size (86.85 ± 1.89 nm) and a two-fold higher antibacterial potency against Escherichia coli (E. coli) than free SPFX. Mechanistically, the solid lipid core locked SPFX in a safe amorphous state to preclude crystal-induced irritation, while functioning as a physical photoshield against UV activation. By depositing the nanomedicine exclusively into infected dermis, the MN platform minimized systemic drug exposure. In a rat model of E. coli-infected biofilm wounds, the formulated SPFX-SLNs MNs achieved over 50% (58.44%) wound closure within 3 days and near-complete re-epithelialization by day 11, and a 98.61% final closure rate by day 14. Ultimately, this work establishes a comprehensive formulation development strategy for a safety-enhanced, biofilm-penetrable nanomedicine-MN hybrid that successfully repurposes a clinically restricted antibiotic for advanced wound regeneration.

The anhydrous salt of sparfloxacin [5-amino-1-cyclo-propyl-7-(3,5-dimethylpiperazin-1-yl)-6,8-di-fluoro-4-oxo-1,4-di-hydro-quinoline-3-carb-oxy-lic acid] with 4-amino-salicylic acid, C22H22F2N4O3 +·C7H6NO3 -, features both inter-molecular (N-H⋯O) and intra-molecular (O-H⋯O) inter-actions. In the crystal, two sparfloxacin and two 4-amino-salicylic acid mol-ecules inter-act with each other through N-H⋯O hydrogen bonds, forming an R 4 4(12) ring motif. The network of inter-molecular inter-actions was further examined using Hirshfeld surface analysis and two-dimensional fingerprint plots.

A novel enantioselective open-tubular capillary electrochromatography (CEC) column was fabricated by noncovalently immobilizing (+)-diacetyl-L-tartaric anhydride functionalized NH2-MIL-101(Fe) onto the capillary inner wall using polydopamine as an adhesive layer. The coating of the modified capillary was comprehensively characterized through Fourier-transform infrared spectroscopy, powder X-ray diffraction, Brunauer-Emmett-Teller analysis, scanning electron microscopy, energy dispersive X-ray spectroscopy, circular dichroism, and electroosmotic flow measurements. The column's chiral separation ability was assessed by analyzing seven model compounds, comprising four proton pump inhibitors (omeprazole, pantoprazole, lansoprazole, and tenatoprazole) and three fluoroquinolones (ofloxacin, sparfloxacin, and gatifloxacin). Under optimized conditions, baseline resolution (9.68-14.56) of all enantiomers was achieved within 7 min. The column demonstrated excellent reproducibility, with inter-day, intra-day, and column-to-column relative standard deviations ranging from 1.22% to 4.98%. Additionally, molecular docking simulations were conducted using AutoDock Tools to investigate interactions between the stationary phase and analyte enantiomers, with computational results corroborating experimental CEC data.

Onchocerciasis and lymphatic filariasis (LF) cause a significant global public health burden with more than 900 million individuals at risk and over 60 million people living with symptomatic manifestations caused by filarial diseases. Due to the importance of Wolbachia for the survival of adult filarial nematodes, anti-Wolbachia therapy has been validated as a safe macrofilaricidal treatment for LF and onchocerciasis. The A-WOL consortium was established with the goals of defining registered anti-Wolbachia antibiotics, as well as developing new drugs effective in a regimen of 7 days or less. We have previously shown autophagy has a core role in the regulation of Wolbachia populations across a diverse range of associations. In this study, we investigated the role of autophagy in the efficacy of anti-Wolbachia drugs.

This study evaluated 65 commercially available pet feed samples, including 33 cat feeds and 32 dog feeds (dry and wet formulations), for the presence of organic contaminants. These included mycotoxins, pesticides, pharmaceutical residues/veterinary drugs, and plant-based bioactive compounds. A suspect screening strategy was employed using QuEChERS extraction followed by LC-LTQ/Orbitrap HRMS analysis. A total of 29 compounds were tentatively identified within 186 detections. In total, 76.9% of the samples were contaminated with mycotoxins. Aflatoxins (B1, B2, G1, and G2), T2 toxins, and HT2 toxins were dominant, with Aflatoxin B1 occurring in 33.8% of the samples and exhibiting a higher prevalence in dry feeds than in wet feeds. Pesticides were present in 72.0% of the dry formulations, including aclonifen and pirimiphos-methyl, but were present in only 11% of the wet formulations. Plant-based bioactive compounds, including phytoestrogens, were identified in 51% of the samples, highlighting toxicologically relevant candidates that merit prioritization for targeted confirmation, particularly in cat feeds. Pharmaceuticals were found in 23.8% of dry feeds (sparfloxacin and fumagillin). Overall, the HRMS-based, standard-free suspect screening workflow provides an early-warning overview of multi-class co-occurrence patterns in complex pet feed matrices and supports the prioritization of candidates for subsequent confirmatory analysis.

Platostoma palustre (Blume) A. J. Paton (or Mesona chinensis Benth.), a traditional medicinal and edible plant in China, possesses significant economic and market potential. To investigate the underlying mechanism of seed aging in P. palustre, we utilized artificial aging technology to induce seed aging and assessed seed viability. Furthermore, we employed transcriptome and metabolome sequencing technologies to analyze gene expression and metabolic alterations in artificially aged seeds. The results showed that the germination rate, germination potential, and germination index of the P. palustre seeds decreased significantly after the aging treatment. Transcriptome analysis identified 2,127 differentially expressed genes (DEGs), consisting of 1,623 up-regulated and 504 down-regulated genes. Metabolomic analyses uncovered that a total of 1,919 metabolites were identified under positive ion mode (957) and negative ion mode (962). In total, 747 differentially expressed metabolites (DEMs) were identified, including 362 up-regulated and 385 down-regulated metabolites. An integrative analysis of transcriptome and metabolome indicated that only one pathway (ABC transporters) was significantly enriched in both DEMs and DEGs, and this pathway included 9 DEMs (Deoxyuridine, L-Glutamine, Sparfloxacin, L-Threonine, L-Histidine, Uridine, Guanosine, Ciprofloxacin, and D-Sorbitol) and 6 DEGs (Mesona_chinensis0082240.1, Mesona_chinensis0452530.1, Mesona_chinensis0457550.1, Mesona_chinensis0440370.1, Mesona_chinensis0324680.1, and Mesona_chinensis0233350.1). Further network analyses showed correlations between the 5 DEGs (except for Mesona_chinensis0324680.1) and 9 DEMs. It was inferred that the ABC transporters pathway and its related genes and metabolites might play an important role in seed aging in P. palustre. The current study laid the foundation for an in-depth investigation of the aging mechanism and safe storage of P. palustre seeds.

Alzheimer's disease (AD) involves progressive cholinergic degeneration, with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) playing key enzymatic roles in its pathology. In this study, we computationally repurposed four FDA-approved quinolone antibiotics, Norfloxacin, Sparfloxacin, Gatifloxacin, and Nalidixic acid, as potential dual-site cholinesterase (ChE) inhibitors using a hybrid in vitro/in silico workflow. Enzyme inhibition assays identified Norfloxacin as the most potent AChE inhibitor (KI = 1.08 μM), while all compounds displayed non-competitive inhibition toward BChE. Molecular docking and MM-GBSA binding free energy analyses revealed key interactions within the catalytic gorge of AChE, supported by hydrogen bonding with Phe295 and Arg296, as well as π-π contacts with Tyr124. Density functional theory computations highlighted the influence of frontier orbital distribution on binding affinity, particularly for Norfloxacin and Sparfloxacin. An explicit-solvent molecular dynamics simulation of the AChE-Norfloxacin complex further confirmed the stability of the docking-derived binding mode over 100 ns. In an exploratory fashion, SHAP-based machine learning models were applied to a descriptor set derived from QikProp, SwissADME, and Jaguar outputs, suggesting that BBB-related indices and HOMO energy contribute to AChE inhibition, whereas the energy gap is more relevant for BChE; these trends, however, are constrained by the small four-compound dataset and should be regarded as hypothesis-generating. In silico ADME/Tox profiling indicated favorable oral drug-like properties, low predicted CYP450 inhibition liabilities, and physicochemical profiles compatible with CNS-oriented optimization, although passive BBB permeability was not predicted to be high. Finally, systems-level enrichment (STRING, GeneCards) provided a qualitative network context linking ACHE and BCHE to neurodegeneration. Together, these data position Norfloxacin and Sparfloxacin as computationally prioritised candidates whose ChE-related repurposing potential warrants further validation in dedicated cellular and in vivo models.

Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) can lead to various genital and extragenital infections, with antibiotic resistance growing and varying wordwide. This study aims to investigate the prevalence and antibiotic resistance profiles of MH and UU in outpatients in Shanghai, China, from 2020 to 2023. A facility-based cross-sectional study was conducted from January 1, 2020 to December 31, 2023. Trends of MH, UU and coinfection (MH and UU coinfection), rate of antibiotic resistance during 2020 and 2023 were analyzed based on Cochran-Armitage trend test. We analyzed the prevalence and antibiotics resistance rate base on chi-square test or a single sample t-test. Our study indicated that the overall positive rate of MH, UU and coinfection were 13.47%, 32.13%, and 11.21%, respectively. For age, the trend of positive rate of UU decreased significantly (Z = -3.62, P < .001). Furthermore, the positive rate of UU increased from 31.82% in 2020 to 47.92% in 2023 (Z = 1.98, P < .05). During 2020 and 2023, Methomycin and strong bacteriocins maintained high activity against both MH and UU, with resistance rates <5%. But roxithromycin (85.48%), azithromycin (75.81%), and levofloxacin (70.97%) showed limit activity for MH, and levofloxacin (44.78%), sparfloxacin (37.36%), and azithromycin (29.40%) showed limit activity for UU. Between 2020 and 2023, the rate of antibiotic resistance to azithromycin, clarithromycin, roxithromycin, methomycin, strong bacteriocins, sparfloxacin, and levofloxacin decreased against MH. The rate of antibiotic resistance to levofloxacin decreased against UU, but increased to josamycin against UU. Josamycin, methomycin, and strong bacteriocins are promising antibiotics against MH and UU. The prevalence of MH and UU should pay more attention in China. Josamycin, methomycin, and strong bacteriocins maintained outstanding activity against MH and UU, although the resistance rate of MH to josamycin increased.

Tumor-resident microbiotas critically influence breast cancer progression and metastasis. To simultaneously eliminate intratumoral bacteria and induce tumor cell death, we developed pH-sensitive nanoparticles (PEPCA@SPA/Fe3+ NPs) by encapsulating sparfloxacin (SPA)-ferric ion (Fe3+) nanoparticles (NPs) within an amphiphilic polyethylene glycol-poly (cinnamyl aldehyde) (PEPCA) copolymer assembly. The PEPCA@SPA/Fe3+ NPs exhibit dual functions including antibacteria and tumor ferroptosis induction. When PEPCA@SPA/Fe3+ NPs entered the acidic environment of tumor cells, SPA/Fe3+ NPs were released, which could effectively eradicate intratumoral bacteria and oxidize glutathione (GSH), thus inactivating glutathione peroxidase-4 (GPX4) and triggering lipid peroxidation and ferroptosis of tumor cells. In orthotopic breast cancer models, intravenously administrated PEPCA@SPA/Fe3+ NPs effectively accumulated in tumor tissues and suppressed primary tumor growth, and significantly reduced lung metastasis by remodeling the intratumoral microbiota. Furthermore, the PEPCA@SPA/Fe3+ NPs formulation well synergized with α-CD47 immunotherapy to activate antitumor immunity by promoting the maturation of dendritic cells (DCs), inducing M1 polarization of tumor-associated macrophages (TAMs), down-regulating regulatory T cells (Tregs) and enhancing cytotoxic T cells. Collectively, this nano-platform provides a promising strategy for concurrent microbial elimination and ferroptosis induction in cancer therapy.

This study aimed to improve the solubility and delivery of sparfloxacin, a poorly soluble quinolone antibiotic, by forming ionic liquids (API-ILs) with hydrophilic quaternary ammonium salts differing in alkyl chain length and hydroxyl group presence. The resulting sparfloxacin-ILs (N6SPAR, N10SPAR, N6OHSPAR, N10OHSPAR) were synthesized with yield of (72 ± 6)% for N6SPAR, N10SPAR, N10OHSPAR and 44 % for N6OHSPAR. Solubility in water, ethanol, and 1-octanol was assessed using dynamic and spectrophotometric methods, with N6SPAR showing the highest water solubility. Differential Scanning Calorimetry (DSC) revealed differences in melting behavior among the derivatives. Lipid-based carrier studies indicated that longer alkyl chains enhance lipid incorporation, while hydroxyl groups reduce it. Biological assays showed no significant cytotoxicity, with cell viability remaining above 50 % at concentrations up to 200  µM, and preserved antibacterial activity, with MICs of 61  nM (E. coli), 488  nM (S. aureus), and 1950  nM (P. aeruginosa). Increased efficacy was observed for N6OHSPAR against E. coli (twofold) and reduced for N6SPAR against P. aeruginosa (fourfold). These findings highlight the potential of IL cation modification to fine-tune solubility and bioactivity, supporting their use in advanced drug formulations where conventional approaches are insufficient.

The progression of ulcerative colitis (UC) involves immune dysregulation, intestinal barrier dysfunction, and microbial dysbiosis while existing targeted therapies present challenges, including adverse effects and economic burdens. UC is characterized by persistent intestinal inflammation, manifesting as abdominal pain, hematochezia, and malnutrition. Prolonged uncontrolled inflammation may lead to colorectal cancer or severe complications, significantly impairing quality of life. Recent studies have revealed a significant correlation between pathological accumulation of senescent cells and UC pathogenesis, suggesting anti-senescence therapeutics as potential interventions. In this study, we identified sparfloxacin (SPA), a fluoroquinolone antibiotic, through high-throughput screening as an effective senolytic agent that markedly alleviates DSS-induced murine colitis. Mechanistically, combining cellular and animal experiments with transcriptomic, untargeted metabolomic, and metagenomic analyses, we demonstrated sparfloxacin's tripartite therapeutic effects: ① Senescence inhibition via downregulation of p16/p21 expression; ② Effective suppression of aberrant JAK/NF-κB signaling activation with a concomitant reduction in pro-inflammatory cytokines (TNF-α, IL-6); ③ Gut microbiota remodeling characterized by increased probiotic abundance and elevated levels of beneficial metabolites. This study for the first time elucidates the molecular mechanism whereby SPA ameliorates UC through coordinated multi-target actions involving senescence inhibition, anti-inflammatory effects, and microbiome restoration. Our findings not only expand the clinical applications of fluoroquinolones but also provide a theoretical foundation for developing integrated UC treatment strategies targeting cellular senescence.

The practical application of conventional photocatalytic technologies in aquatic environmental remediation is significantly limited by rapid charge recombination and insufficient redox capacity. Theoretical calculations and experimental characterization confirmed that the synergistic co-doping of boron (B) and bismuth (Bi) induced tailored modifications to the band structures and Fermi level potential of g-C3N4 (CN) and ZnIn2S4 (ZIS), respectively, successfully transforming the type-II CN/ZIS heterojunction into an S-scheme B-doped CN/Bi-doped ZIS (BCN/BZIS) heterojunction. The subsequent integration of Cd0.5Zn0.5S (CZS) into the BCN/BZIS heterojunction introduced additional type-II and S-scheme photogenerated carrier transfer pathways, thereby establishing a hybrid BCN/BZIS/CZS heterojunction. This configuration exhibited exceptional reduction capacity and optimized photogenerated carrier separation and migration efficiency, leading to excellent degradation performance for gatifloxacin ((26.89 ± 1.94) × 10-2 min-1), sparfloxacin ((10.48 ± 2.03) × 10-2 min-1), moxifloxacin ((8.43 ± 1.02) × 10-2 min-1), and gemifloxacin ((4.13 ± 0.13) × 10-2 min-1). The degradation disparities among these quinolone antibiotics were systematically elucidated through analyses of steric hindrance, frontier molecular orbital energies, Mulliken charge distribution, reaction sites, and active species contribution rates. This study offers guidance for the systematic development of heterojunction photocatalysts to address fluoroquinolone pharmaceutical pollutants in aquatic ecosystems.

Background: Fluoroquinolones, available in topical and oral formulations, are used to manage bacterial skin and soft tissue infections, including Pseudomonas aeruginosa, atypical mycobacteria, and select multidrug-resistant Gram-negative organisms. Their excellent tissue penetration, bactericidal activity, and convenient dosing make them effective for certain skin and soft tissue infections. However, their use is limited by potential safety concerns, including tendinopathy (odds ratio up to 9.1 in corticosteroid users), QT interval prolongation with risk of torsades de pointes, phototoxicity, and rising antimicrobial resistance. Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for articles from January 1985 to April 2025 with the search terms (quinolone OR fluoroquinolone) AND (dermatology OR "skin and soft tissue infection" OR "skin structure infection"). Abstracts and presentations were excluded. A Google search used the same terms for articles from government regulatory agencies. Results: This review provides practical guidance on the clinical use of topical and oral fluoroquinolones in dermatology. Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections. However, serious safety concerns remain, including a ninefold increase in tendinopathy risk among older adults on corticosteroids and corrected QT intervals exceeding 500 milliseconds in high-risk patients. Phototoxicity varies, with agents like sparfloxacin linked to heightened ultraviolet sensitivity. Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations. Culture-based prescribing, shorter treatment courses, and preference for topical treatments can reduce risk and preserve efficacy. Conclusions: Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts.