Lumpy skin disease virus (LSDV) is capable of causing transboundary diseases characterized by fever, nodules on the skin, mucous membranes, and inner organs. The disease may cause emaciation with the enlargement of lymph nodes and sometimes death. It has had endemic importance in various parts of Asia in recent years, causing substantial economic losses to the cattle industry. The current study reported a suspected LSDV infection (based on signs and symptoms) from a mixed farm of yak and cattle in Sichuan Province, China. The clinical samples were found positive for LSDV using qPCR and ELISA, while LSDV DNA was detected in Culex tritaeniorhynchus Giles. The complete genome sequence of China/LSDV/SiC/2021 was determined by Next-generation sequencing. It was found that China/LSDV/SiC/2021 is highly homologous to the novel vaccine-related recombinant LSDV currently emerging in China and countries surrounding China. Phylogenetic tree analysis revealed that the novel vaccine-associated recombinant LSDV formed a unique dendrograms topology between field and vaccine-associated strains. China/LSDV/SiC/2021 was found to be a novel recombinant strain, with at least 18 recombination events via field viruses identified in the genome sequence. These results suggest that recombinant LSDV can cause high mortality in yaks, and its transmission might be due to the Culex tritaeniorhynchus Giles, which acts as a mechanical vector.

Heavy metal pollution is a serious environmental concern worldwide. Cadmium is one of the most common and hazardous heavy metals and is known to impair intestinal barrier integrity. Therefore, this study was designed to evaluate the protective effects of Lactobacillus plantarum against cadmium chloride (CdCl₂)-induced toxicity in chickens. A total of 120 one-day-old Arbor Acres broiler chickens were randomly divided into four equal groups (n = 30 birds/group). Following a 4-day acclimation period, the chickens were subjected to a 28-day feeding trial. The control group (CON) received a standard basal diet, the probiotic group (LB) received L. plantarum at 1 × 10⁸ CFU/mL via oral gavage, the co-treatment group (LC) received L. plantarum at 1 × 10⁸ CFU/mL together with CdCl₂ at 80 mg/kg, and the toxin group (CD) received CdCl₂ at 80 mg/kg. Cadmium exposure markedly increased mortality, reduced survival rates, elevated serum liver enzyme activities (p < 0.0001), increased cadmium accumulation in tissues (p < 0.05), and decreased body weight gain in chickens (p < 0.0001). Moreover, cadmium exposure was associated with altered tissue Ca²⁺ homeostasis, upregulation of PIEZO1 expression and impairment of the epithelial tight-junction proteins, including ZO-1, occludin, and claudin-1. In contrast, L. plantarum supplementation improved intestinal barrier integrity and restored intestinal morphology, including villus height and crypt depth, which were adversely affected by cadmium exposure. Collectively, L. plantarum supplementation attenuated cadmium-induced systemic and intestinal toxicity, as evidenced by multiple protective mechanisms, such as reduced mortality, decreased tissue cadmium accumulation (p < 0.05), improved biochemical parameters, and preservation of intestinal morphology and tight-junction integrity. These findings suggest that L. plantarum may provide a potential dietary strategy for mitigating cadmium toxicity in broiler chickens.

Lumpy skin disease virus (LSDV), a capripoxvirus that causes substantial animal-health and economic losses in cattle, remains a major veterinary concern, with few specific antiviral options available. Here, a series of semi-synthetic Tylosin A derivatives were evaluated for anti-LSDV activity using an LSDV-eGFP infection model in Madin–Darby bovine kidney cells. Initial screening identified T3 and T8 as the most active derivatives, reducing infectious virus production by 89.6% and 91.0%, respectively, at 200 ppm. Dose–response analysis based on infectious-virus titration yielded IC₅₀ values of 23.02 ppm (95% CI, 18.48–28.33) for T3 and 19.13 ppm (95% CI, 13.87–25.32) for T8. The corresponding CC₅₀ values were 748.3 and 621.4 ppm, resulting in selectivity indices of 32.50 and 32.48, respectively. Mechanistic studies focusing on T3 showed that antiviral activity was most pronounced when the compound was administered after viral entry and during the early post-infection period. T3 reduced viral genomic DNA accumulation beginning at 8 h post-infection while largely preserving early viral gene transcription and suppressing DNA-replication-dependent intermediate and late gene expression. This phenotype closely resembled that induced by the DNA synthesis inhibitor cytarabine (AraC), supporting an inhibitory effect of T3 at or upstream of the viral DNA replication stage. Proteome-wide molecular docking did not reveal preferential docking of T3 to the selected viral DNA replication-associated proteins, and direct target engagement remains to be established. Collectively, these findings identify T3 and T8 as promising anti-LSDV lead compounds and support further optimization of the Tylosin A scaffold, while mechanistic studies suggest that T3 exerts its antiviral effects primarily during the viral DNA replication phase.

Background: Antimicrobial resistance among Gram-positive veterinary pathogens has increased the need for more rational and experimentally grounded strategies to prioritize tylosin derivatives for antibacterial development. This study aimed to develop and externally a calibrated, decision-oriented screening workflow for tylosin-derived antibacterial analog prioritization against Staphylococcus aureus and Streptococcus agalactiae. Methods: Publicly available minimum inhibitory concentration (MIC) data were used to construct organism-specific multilayer perceptron models. Model performance was evaluated using a five-fold out-of-fold framework. Calibrated activity probabilities were then combined with precision-oriented thresholds and similarity-based applicability-domain constraints to define prospective Go/No-Go decisions. To examine external transferability, six synthesized tylosin derivatives (A1–A6) were prospectively predicted and subsequently tested using in vitro MIC assays. Results: Internal validation showed stronger and more stable performance for S. aureus than for S. agalactiae. However, closed-loop external validation revealed distinct organism-specific decision behaviors. For S. aureus, the workflow assigned Go decisions to five compounds and included the only experimentally active analog, A6, but also generated several false Go decisions for inactive analogs. For S. agalactiae, all six compounds were classified as No-Go under the primary decision rule, whereas MIC testing showed that four analogs were experimentally active, indicating conservative under-selection in a low-data extrapolation setting. Conclusions: Calibrated probabilities and applicability-domain analysis can improve the transparency and diagnostic value of antibacterial prioritization, but they do not guarantee robust external activity prediction when training-set coverage, threshold transferability, or chemical-space representation is limited. Overall, this study provides an early-stage, risk-aware closed-loop decision-support framework for tylosin-derived analog prioritization and highlights the need for iterative model updating, probability recalibration, and larger external validation before such workflows are used as high-confidence prospective screening tools in veterinary antibacterial discovery.

The purpose of this study was to use data mining and network pharmacology to determine drug patterns for bovine viral diarrhea (BVD). The frequency, properties, tastes, meridian tropism, and functions of prescription data were gathered and examined from four literature databases (2004–2024). Cluster analysis was used to find prescription patterns, and the Apriori algorithm (SPSS Modeler 18) was used to find associations. A total of 391 literature-derived prescription records were included in the analysis, involving 189 distinct herbal medicines and a cumulative herb-use frequency of 2031 occurrences. These herbs primarily enter the liver meridian and were categorized as cold, warm, or neutral. The predominant tastes were bitter, pungent, and sweet. Five frequently recorded herbs and 14 co-occurrence patterns among herbs were extracted. According to traditional Chinese medicine (TCM), spleen–stomach deficiencies and damp-heat pathogens are linked to BVD. These medication patterns were mainly associated with heat-clearing, detoxification, spleen-strengthening, and Qi-regulating strategies in TCVM theory. Targets were screened, PPI networks were constructed, and enrichment studies for core herbs (Baitouweng, Huangbo, Huangqin, Qinpi, and Zhizi) were performed using network pharmacology. The binding affinities between disease targets and active components were further assessed using molecular docking. The findings provide a descriptive summary of medication patterns and generate preliminary hypotheses regarding potential compound–target–pathway associations involved in the symptomatic and supportive use of TCM for BVD.

This review summarizes the research progress on inhibitors of lumpy skin disease virus (LSDV), focusing on its biological characteristics and key proteins involved in the viral replication cycle. It compiles various inhibitors (direct‐acting poxvirus inhibitors and host‐directed poxvirus inhibitors) against poxviruses, their mechanisms of action, and potential targets, aiming to provide references for the development of LSDV inhibitors. Additionally, the application of computer‐aided drug design methods in anti‐LSDV inhibitor research is discussed, offering insights from the perspective of virtual screening to facilitate the discovery of novel antiviral agents.