Albendazole sulfoxide (ABZSO), the pharmacologically active metabolite of albendazole, exhibits favorable tissue distribution but its pharmaceutical application is constrained by poor aqueous solubility. In this study, an optimized binary solid dispersion (SD) of ABZSO was prepared by the fusion method using poloxamers P188 and P407 at an 8:1 ratio, with a drug-to-carrier ratio of 1:3. The optimized formulation achieved rapid drug release, with a cumulative dissolution of 99.39% within minutes, and increased the apparent solubility of ABZSO to 105 mg·L-1. Solid-state characterization by differential scanning calorimetry, X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy demonstrated that ABZSO was present in a partially amorphous, mixed-phase state, with residual crystallinity semi-quantitatively estimated as 21.80% and 32.33% as determined by DSC and XRD, respectively. The optimized formulation showed acceptable batch-to-batch reproducibility and maintained acceptable short-term dissolution performance under stress conditions, although further optimization of long-term physical stability remains necessary. In a goat pharmacokinetic study, the ABZSO-SD significantly enhanced systemic exposure and achieved a relative oral bioavailability of 120.55% compared with the laboratory-prepared suspension (P < 0.01). Overall, these findings demonstrate that the optimized ABZSO-SD formulation effectively improves the solubility, dissolution performance, and oral absorption of ABZSO, providing a potential formulation strategy for enhancing ABZSO bioavailability in ruminants.

Canine mammary tumours (CMTs) and human breast cancer (HBC) share highly similar pathological characteristics. Cancer stem cells (CSCs) are critical to breast cancer invasion, metastasis, drug resistance, and recurrence. The experiment utilised CMT cell line CMT-U27 and HBC cell line MDA-MB-231. Cancer stem cell spheres were isolated from the two cell lines by serum-free culture respectively, named as CMT-U27 microspheres (CMT-U27S) and MDA-MB-231 microspheres (MDA-MB-231S), and the proportion of CSCs with the CD44+/CD24- phenotype was identified by flow cytometry. Monensin (MON), one of Polyether ionophore antibiotics, has been demonstrated to effectively suppress various types of CSCs, while erlotinib (ERL), as a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR), effectively inhibits cancer cell growth. This study investigates the synergistic inhibitory effects of MON-ERL combination on CSCs derived from CMTs. Cell viability was analysed by CCK-8 assay, while cell invasion and mammosphere formation assays were conducted to evaluate changes. An orthotopic tumour model in nude mice using CMT-U27S was established for in vivo validation. The results suggested that MON and ERL combination synergistically inhibited CSCs viability and significantly suppress their invasion and mammosphere formation abilities. The expression of key proteins of the EGFR pathway-p-EGFR, PI3K, and p-AKT was significantly reduced. In animal experiments, tumour volumes in the combination treatment group were markedly reduced compared to those in all other groups (p < 0.05), and no lung metastases were observed only in the combination group. Immunofluorescence and immunohistochemistry results indicated a marked reduction of CD44+/CD24- cells in the combination group, along with suppressed expression of stem cell markers and proliferation/apoptosis proteins. In conclusion, MON combined with ERL effectively inhibits the proliferation, self-renewal, and metastatic capabilities of CSCs from CMTs by synergistically downregulating the EGFR/PI3K pathway, demonstrating promising antitumor potential and offering a new strategy for CMTs treatment.

Polystyrene micro/nanoplastics (PS-MPs/NPs) and the neonicotinoid imidacloprid (IMI) frequently co-occur in freshwater ecosystems, yet their combined toxicity profiles remain distinct and unresolved. Here, we exposed juvenile crucian carp (Carassius auratus) to PS-MPs (5 μm), PS-NPs (60-100 nm), and IMI, alone or in combination, to unravel their interactive mechanisms via a multi-omics approach. Results revealed a clear size-dependent toxicity pattern: while PS-NPs (especially with IMI) preferentially targeted the brain, PS-MPs (with or without IMI) induced the most severe intestinal histological injury, characterized by extensive intestinal fold atrophy and goblet cell depletion. In the brain, co-exposure to PS-NPs and IMI elicited potentiated neurotoxicity, manifesting as blood-brain barrier (BBB) breakdown, neuroinflammation, and a specific disruption of the glutamate-glutamine-γ-aminobutyric acid (Glu-Gln-GABA) metabolic cycle, which coincided with hyperactive and asocial behaviors. Microbiome analysis highlighted distinct dysbiotic signatures. Integrated network analyses further linked these gut microbial shifts to central neurochemical imbalances, implicating the microbiota-gut-brain axis as a potential pathway involved in systemic toxicity. In summary, this study differentiated between gastrointestinal damage caused by MPs and systemic combined toxicity caused by the penetration of NPs and IMI across biological barriers. It emphasizes the importance of size-specific assessment in understanding the complex risks of combined exposure to plastics and pesticides, providing insights for pollution management in agricultural hotspots.

Ferroptosis is a promising programmed cell death modality for cancer therapy, driven by iron overload and the accumulation of phospholipid peroxides that culminate in lethal membrane damage. Over the past decade, emerging evidence supports the concept that ferroptosis can be harnessed as an effective strategy to suppress tumor growth, particularly in therapy-resistant cancer cells undergoing epithelial–mesenchymal transition and in cancer stem cells. Given that ferroptosis is mechanistically and morphologically different from other known programmed cell death forms, increasing critical findings have shed light on mechanisms by which ferroptosis is regulated, and context-dependent cancer phenotype which is clinical relevant to ferroptosis. In this review, we summarize the basic biology of ferroptosis, including iron regulation and lipid metabolism, as well as key molecular mechanisms such as the system Xc⁻-GSH-GPX4, NADPH-FSP1-CoQ10 and GCH1-BH4 axis in fighting cancer. We also discuss crosstalk between ferroptosis and cuproptosis, disulfidptosis and autophagy, and outline how ferroptosis shapes the tumor immune microenvironment and responses to immunotherapy. More importantly, we highlight the clinical potential of ferroptosis induction via chemotherapy, radiotherapy, immunotherapy and nanomedicine-based delivery strategies, while summarizing common resistance mechanisms and safety considerations. Finally, we outline major challenges and pressing questions for clinical translation, including what are the molecular bases of ferroptosis, how can ferroptosis be leveraged for cancer therapy, how can ferroptosis be integrated with conventional therapies, and how to balance benefits and risks of ferroptosis-based therapy. Collectively, this review connects mechanistic insights with actionable intervention points for developing ferroptosis-based cancer therapies.

Salmonellosis remains one of the most prevalent bacterial enteric diseases in swine production worldwide. Tilmicosin (TMS) is widely used in swine bacterial infections, but its oral application is limited by gastric degradation and intense bitterness, reducing bioavailability and therapeutic efficacy. This study aimed to develop and evaluate pilot-scale TMS-loaded nanostructured lipid carriers (TMS@NLCs) to overcome these obstacles. Herein, TMS@NLCs were fabricated at 100-L scale via high-pressure homogenization. Physicochemical properties of TMS@NLCs were characterized, along with stability in simulated gastrointestinal fluids and in vitro antibacterial activity. Palatability was assessed by piglet drinking behavior and electronic tongue. Pharmacokinetics and therapeutic efficacy against Salmonella infection were evaluated in piglets. TMS@NLCs exhibited uniform spherical morphology with mean diameter 231.9 ± 33.3 nm, high encapsulation efficiency (95.50 ± 3.31%) and drug loading (4.703 ± 0.179%). Notably, they also showed excellent gastric stability, and superior taste-masking evidenced by reduced bitterness and 34% higher water intake versus commercial TMS solution. TMS@NLCs enhanced intracellular Salmonella clearance and increased oral bioavailability. In Salmonella-infected piglets, TMS@NLCs significantly reduced bacterial loads, attenuated inflammation and restored intestinal barrier, with no detectable adverse effects. Together, pilot-scale TMS@NLCs successfully overcome the inherent limitations of pronounced bitterness and gastric instability associated with the raw drug. This formulation demonstrates exceptional performance in enhancing oral bioavailability and antibacterial efficacy, highlighting its substantial potential for clinical veterinary translation.

Bovine viral diarrhea virus (BVDV) is a key member of the genus Pestivirus, which can cause persistent infections (PI) characterized by immunotolerance, leading to significant economic losses to the cattle industry globally. Among the detection methods for BVDV, conventional gold nanoparticles-based lateral flow immunoassay (Au NPs-based LFIA), which uses gold nanoparticles as signal reporters, often suffers from low sensitivity due to insufficient signal brightness. The development of more sensitive point-of-care testing (POCT) methods is urgently needed. In the present study, we developed a novel signal reporter based on Ag-rich Ag-Au nanoshells (AgR-Au NSs) featuring enhanced visual color brightness. The developed AgR-Au NSs-based LFIA enables one-step BVDV detection within 20 minutes. Under optimized conditions, the visual detection limit reached 1.95 × 103TCID50/mL, a four-fold improvement over conventional Au NPs-based LFIA and consistent with ELISA. The assay showed broad reactivity across different BVDV genotypes, no cross-reactivity with other pathogens, and good stability (4 °C for 180 days). In 215 clinical samples, it achieved 98.14

Methuosis represents a novel cell death modality characterized by catastrophic cytoplasmic vacuolization in normal and malignant cells. However, the critical role and the underlying mechanism of cytoskeleton and plasma membrane damage in methuotic cells are largely unknown. We found that cytoskeleton protein F-actin, α-tubulin, β-tubulin and filamin A/B were disrupted in a reversible-dependent manner. In addition, RhoA-ROCK1 signaling pathway mediated cytoskeleton disruption in methuotic cells. Excessive cytoplasmic vacuolization triggered cellular plasma membrane damage and the release of damage associated molecular patterns (DAMPs), including lactate dehydrogenase (LDH), adenosine triphosphate (ATP) and calreticulin (CRT). Furthermore, at the end phase of methuotic cells, plasma membrane was damaged independent of pore-forming protein phosphorylation mixed lineage kinase domain-like (p-MLKL) and gasdermin D (GSDMD). Endosomal sorting complex required for transport (ESCRT)-III especially its subunit charged multivesicular body protein 3 (CHMP3) and charged multivesicular body protein 5 (CHMP5) negatively regulated excessive vacuolization-induced plasma membrane damage in cells undergoing methuosis. The critical role and potential mechanism of cytoskeleton and plasma membrane damage in methuotic cells are known, which would facilitate the employment of methuosis in life science and pharmacology.

Coronaviruses often cross species barriers, with receptor binding dictating their host range and zoonotic potential. Merbecoviruses, such as MERS-CoV, typically utilize DPP4 as their receptor, whereas Sarbecoviruses, like SARS-CoV, rely on ACE2. This study explores the receptor usage of four merbecoviruses identified in Vespertilionidae bats: HKU5, BtVs-SC2013, HKU25, and P. khulii-2011. Our findings reveal species-specific binding to bat ACE2: HKU5 binds exclusively to Pipistrellus abramus ACE2, P. khulii-2011 interacts solely with Murina aurata ACE2, BtVs-SC2013 recognizes ACE2 from Murina aurata and Myotis myotis, and HKU25 displays the broadest binding range. Beyond bats, BtVs-SC2013 binds to mink ACE2, while HKU25 interacts with both mink and pangolin ACE2, hinting at potential intermediate hosts for cross-species transmission. We also elucidated the mechanism behind HKU5's selective binding preference for P. abramus ACE2. Structural analysis and mutagenesis revealed that a carbohydrate attached at position 329 play a crucial role. Introducing the N-glycosylation site into P. abramus ACE2 eliminated binding, while its removal from P. pipistrellus ACE2, combined with two additional mutations, restored it. Moreover, we pinpointed key residues in mink ACE2 essential for binding the receptor-binding domain (RBD) of BtVs-SC2013 and HKU25. These findings illuminate the receptor usage and host specificity of bat merbecoviruses, enhancing our understanding of their potential for cross-species transmission and adaptation.

Hemostatic materials should have efficient and rapid hemostasis, good biocompatibility, and nontoxicity. However, common hemostatic sponges often fail due to their weak mechanical strength, low biocompatibility, and slow hemostasis. Herein, we have developed novel and multifunctional chitosan/cellulose/tannic acid (CS/OMCC/TA) biocomposite sponges by a freeze-drying method without adding any chemical cross-linking agents. The water absorption rate of the biocomposite sponge is as high as 4404%, and the blood absorption rate is as high as 5460%. In vitro coagulation tests have shown that the coagulation ability of CS/OMCC/TA biocomposite sponges is significantly better than that of commercial hemostasis materials. DPPH radical scavenging test and antibacterial experiments demonstrated excellent antioxidant properties and inhibitory effects on Staphylococcus aureus and Escherichia coli. Animal experiments showed that CS/OMCC/TA biocomposite sponges could rapidly hemostasize within 185 s and the blood loss was as low as 107 mg. These findings provide biocompatible and rapid hemostatic materials for the daily emergency trauma treatment and surgical hemostasis.

Cancer cells possess a negatively charged surface that significantly influences key biological processes, including motility and invasiveness. Understanding the cellular membrane at the nanoscale level, especially in deciphering tumor migration mechanisms, is crucial yet complex. In this study, we explored the impact of maduramicin (MAD), a polyether ionophore antibiotic, on the surface charge distribution in tumor cell membranes. Our findings demonstrated that modulating calcium channels and disrupting charge distributions, imaged by a current difference-based scanning ion conductance microscopy (Delta I-SICM) method, resulted in significant reductions in both cell invasiveness and viability. These results emphasize the cell membrane's considerable role at the nano-bio interface, highlighting the intricate relationship between biophysical properties and cellular behaviors. Our research suggests that targeting the charge distribution of cell membrane may offer a novel therapeutic strategy to mitigate cell migration and enhance treatment outcomes in cancer therapy.

Nanoparticle-based transdermal drug delivery systems (TDDS) have emerged as a revolutionary approach for antiparasitic therapy, addressing key challenges such as poor bioavailability, systemic toxicity, and drug resistance. This review highlights the advancements in nanotechnology-driven TDDS for combating zoonotic parasitic diseases, including leishmaniasis, malaria, and infections treated by broad-spectrum drugs like ivermectin and albendazole. By leveraging nanocarriers such as liposomes, nanoemulsions, and microneedles, which enhance skin permeation, enable controlled drug release, and improve targeting specificity. For instance, deformable transfersomes and ethosomes achieve high transdermal efficiency without chemical adjuvants, while microneedle arrays physically bypass the stratum corneum for precise delivery. Furthermore, sustained-release hydrogels and stimuli-responsive nanoparticles optimize therapeutic efficacy and reduce adverse effects. Despite promising results, clinical translation faces challenges in manufacturing scalability, long-term safety, and accessibility in resource-limited settings. Future directions include bioinspired nanocarriers, artificial intelligence (AI)-driven design, and integration with global health initiatives like “One Health”, all aimed at ensuring equitable implementation. This review highlights the transformative potential of nanotechnology in achieving sustainable antiparasitic solutions for zoonotic diseases.

The colonization of bacterial pathogens is a major concern in wound infection and becoming a notable medical issue. Enrofloxacin (ENR) can be applied to treat skin infections, while poor water solubility and bioavailability limit its clinical application. Nanostructured lipid carriers (NLCs) enhance the solubility and bioavailability of drugs by encapsulating them, making them effective for the topical treatment of skin wound infections. Additionally, to enhance treatment efficacy and further improve wound healing, silver nanoparticles (AgNPs) were attached to the aforementioned matrix, which also improved its colloidal stability and reduced toxicity. Herein, a scalable poly (vinyl alcohol) modified NLCs-based antibacterial platform was fabricated by high-pressure homogenization method, to co-load ENR and AgNPs for treating the bacterial-infected wounds. The growth of common wound bacterial pathogens (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) was synergistically inhibited by released ENR and Ag+ from the poly (vinyl alcohol) modified enrofloxacin‑silver composite nano-emulsion (ENR@PVA-NLCs/AgNPs). In the in vivo wound model, the Staphylococcus aureus-infected wound in rat almost completely disappeared after treatment with ENR@PVA-NLCs/AgNPs, and no suppuration symptom was observed. Importantly, this nanoplatform had negligible side effects in vivo. Taken together, the above results strongly demonstrate the promising potential of ENR@PVA-NLCs/AgNPs as a synergistic therapeutic agent for clinical wound infections.

Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans1, the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked2. Here we report the isolation and characterization of a previously undescribed mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia. Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as an entry receptor and can infect mink, bat, monkey and human cells. Cryo-electron microscopy analyses revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as the RBD of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite structural differences. We identify the key determinants on the RBD of MRCoV and ACE2 that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV, uses ACE2 of the bat Pipistrellus abramus for cell entry and requires only two amino acid substitutions to adapt to mink ACE2. SARS-CoV-2 protease and polymerase inhibitors potently block MRCoV infection, thereby indicating a potential therapeutic strategy. Collectively, these findings enhance our understanding of coronavirus receptor dynamics and highlight their zoonotic potential. Given the risks posed by fur farms as reservoirs for emerging pathogens, our study underscores the need for enhanced surveillance to mitigate future coronavirus outbreaks.

Ionophore polyether antibiotics (IPAs) exhibit remarkable therapeutic potential in combating parasitic diseases and cancer, yet their clinical utility is significantly hampered by severe hepatotoxicity. Despite widespread documentation of IPAs-induced hepatotoxicity, the precise molecular mechanisms underlying this phenomenon remain elusive. This study elucidates the role of ferroptosis in IPAs-induced liver injury and delineates the associated regulatory pathways. Through comprehensive in vitro (HepG2 cells) and in vivo (mice) investigations, we demonstrate that IPAs, particularly the highly toxic maduramicin (Mad), induce hepatocyte ferroptosis. Mechanistic studies employing lipid reactive oxygen species (ROS) quantification, intracellular Fe2+ assays, and Western blot analysis revealed that IPAs-induced ferroptosis occurs through an autophagy-dependent pathway. Surface plasmon resonance (SPR) and molecular docking analyses confirmed direct binding and regulation of transcription factor EB (TFEB) by maduramicin. This interaction activates TFEB, subsequently mediating nuclear receptor coactivator 4 (NCOA4)-regulated lysosomal degradation processes that culminate in ferroptosis-mediated hepatotoxicity. Importantly, our findings extend beyond maduramicin, as other IPAs including monensin and salinomycin similarly targeted TFEB, triggering hepatocyte ferroptosis. Crucially, adeno-associated virus serotype 8 (AAV8)-mediated TFEB knockdown in mice conferred protection against IPAs-induced liver injury and attenuated hepatocyte ferroptosis. These findings establish TFEB-mediated NCOA4-dependent ferritinophagy and ferroptosis as central mechanisms in IPAs-induced hepatotoxicity, thereby identifying TFEB as a promising therapeutic target for mitigating IPAs-induced liver damage. This study provides critical insights into the molecular mechanisms of IPAs-induced liver injury and offers a novel strategy for therapeutic intervention.

Canine atopic dermatitis (CAD) is a common skin disease in dogs. Various pathogenic factors contribute to CAD, with dust mites, environmental pathogens, and other substances being predominant. This research involved comprehensive statistical analysis and prediction of CAD in China, using data from 14 cities. A distributed lag nonlinear model (DLNM) was developed to evaluate the impact of environmental factors on CAD incidence. Additionally, a seasonal auto-regressive moving average (ARIMA) model was used to forecast the monthly number of CAD cases. The findings indicated that CAD mainly occurs during June, July, August, and September in China. There was a positive correlation found between CAD incidence and temperature and humidity, while a negative correlation was observed with CO, PM2.5, and other pollutants.

Canine mammary tumor (CMT) is one of the relevant models of human breast cancer (HBC) with histopathological, epidemiological, and clinical characteristics similar to those of humans. This study aimed to establish and characterize a new canine cell line CMT-N7. CMT-N7 tumor is a complex canine mammary carcinoma that stained negative for human epidermal growth receptor-2 (HER2) and progesterone receptors (PR), and positive to estrogen receptor (ER). Cell growth, ultrastructure, doubling time, metastasis capacity, and biomarker characteristics of CMT-N7 were assessed. Xenograft transplantation was conducted to evaluate tumorigenicity. The cell morphology of CMT-N7 was generally epithelioid, with large and irregular nuclei and obvious multinucleation. The established CMT-N7 cell line underwent over 120 generations of subculture, exhibiting a rapid proliferation rate with a doubling time of 20.34h and a chromosome number ranging from 70 to 90. Transwell and wound healing assays demonstrated the CMT-N7 cells had invasive ability. Immunofluorescence analysis revealed positive expression of ER, alpha-SMA, CK-14, SOX-2, Vimentin, Ki-67, E-cadherin, and COX-2 in CMT-N7 cells. Following inoculation with CMT-N7 cells for two weeks, all mice developed tumors. Immunohistochemical analysis showed negative expression of HER-2 and PR, and positive expression of ER, Ki-67, E-cadherin, Vimentin, and COX-2. Consequently, the establishment of the canine mammary cancer cell line CMT-N7 provides a good model for investigating the mechanism of epithelial-mesenchymal transition (EMT) in both dogs and humans.

Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

The efficacy of Mahonia bealei (Fort.) leaves extract (MBLE) against coccidiosis in chickens was studied in vivo. For this purpose, a total of 120 Hyland brown chickens (one-day-old) were randomly divided into six groups, each comprising 20 chickens, viz. MBLE-L, MBLE-M, and MBLE-H; drug control group; infected-untreated group; and uninfected-untreated group. Except for the uninfected/untreated group, the chickens in all other groups received an oral inoculation of 1.0 x 104 pieces/feather sporulated oocysts of E. tenella on day 15. Then, for 7 days in a row, the drug control group was given sulfachloropyrazine sodium soluble powder (1.0 g/day) in drinking water, while the three treatment groups MBLE-L, MBLE-M and MBLE-H were given the MBLE @0.25, 0.5, and 1.0 g/day, respectively. The anticoccidial effects were evaluated by lesion score, body weight gain, oocyst output, and histopathological changes in the liver, kidney, and cecum of the chickens in each group. The results showed that no chickens died in all groups except 2 chickens died in the untreated group. The MBLE groups were able to decrease coccidia oocyst output, mitigate the impact of coccidian infection on chicken weight increase, and lessen pathological alterations in the liver, kidney, and cecum of infected chickens. Among these, the MBLE-H group demonstrated the greatest efficacy with an anticoccidial index of 159.17. Results showed that an extract from Mahonia bealei (Fort.) leaves extract had an anticoccidial effect on chickens infected with E. tenella.

Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.