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Inspired by structures of natural metalloenzymes, a biomimetic synthetic strategy is developed for scalable synthesis of porous Fe-N 3 single atom nanozymes (pFeSAN) using hemoglobin as Fe-source and template. pFeSAN delivers 3.3- and 8791-fold higher oxidase-like activity than Fe-N 4 and Fe 3 O 4 nanozymes. The high catalytic performance is attributed to (1) the suppressed aggregation of atomically dispersed Fe; (2) facilitated mass transfer and maximized exposure of active sites for the created mesopores by thermal removal of hemoglobin (2 ~ 3 nm); and (3) unique electronic configuration of Fe-N 3 for the oxygen-to-water oxidation pathway (analogy with natural cytochrome c oxidase). The pFeSAN is successfully demonstrated for the rapid colorimetric detection of glutathione with a low limit of detection (2.4 nM) and wide range (50 nM–1 mM), and further developed as a real-time, facile, rapid (~6 min) and precise visualization analysis methodology of tumors via glutathione level, showing its potentials for diagnostic and clinic applications. It is needed yet difficult to achieve a strategy for synthesizing single-atom nanozymes that integrate atomic metal dispersion, elevated mass transport and tailorable coordination environment. Here, the authors address this issue by developing a biomimetic synthetic strategy and demonstrate the application of the resultant single-atom Fe nanozymes for tumor visual identification.

Background & Aims Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized. Methods We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored. Results The miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker. Conclusions Our study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies.

A simple and effective method for determining five pyrethroid residues in herbal tea by ultrasound-enhanced temperature-controlled (UETC) ionic liquid dispersive liquid-liquid microextraction (IL-DLLME) coupled with high performance liquid chromatography-diode array detection (HPLC-DAD) was developed. The use of ultrasonication and heating improved the ability of the ionic liquid to extract the analytes. Various parameters that affect the extraction efficiency were investigated and optimized using single factor experiments and response surface design. The optimum conditions of the experiment were 121 µL of [HMIM][PF6] (extraction solvent), 794 µL of acetonitrile (dispersive solvent), a heating temperature of 40°C, a sonication time of 3.6 min and a pH of 2.9. Under optimized conditions, the linearity was in the range of 0.05–5 mg L −1 with correlation coefficients above 0.9993. The limits of detection and quantification were 1.25–1.35 µg L −1 and 5 µg L −1 , respectively. The mean recoveries of the five pyrethroids ranged from 74.02% to 109.01%, with RSDs below 9.04%. The proposed method was reliable for the analysis of pyrethroids in Chinese herbal tea.

Background Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis. Methods The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 10 4 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD). Results The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation. Conclusions The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers. Graphical Abstract

In the field of orchard harvesting, this study proposes a collaborative picking strategy for dual-arm robots, aiming to improve efficiency, reduce labor burden, and achieve precise automation. The strategy combines the Multi-Agent Proximal Policy Optimization (MAPPO) algorithm with the Multi-Objective Greedy Picking Strategy (MOGPS) algorithm. By centrally training the critic network and decentralizing the actor network, the robots can autonomously learn and precisely pick in a simulated environment. To address dynamic obstacle avoidance, a dynamic collision assessment strategy is proposed, and an improved MOGPS algorithm is used to consider the distribution of fruits and the complexity of the working environment, achieving adaptive path planning. Experimental results show that the MAPPO-MOGPS algorithm optimizes the picking path by 15.11%, with a picking success rate as high as 92.3% and an average picking error of only 0.014. Additionally, physical experiments in real-world settings demonstrate the algorithm’s practical effectiveness and generalization.

Background: Porcine circovirus type 2 (PCV2) is the primary pathogen responsible for postweaning multisystemic wasting syndrome (PMWS) and related diseases, leading to significant economic losses in the global pig industry. Methods: This study conducted a thorough epidemiological survey between 2022 and 2024, gathering 6600 samples from 24 large-scale pig farms in Hubei Province. On the basis of these findings, the immune response and economic benefits of two representative commercial PCV2 subunit vaccines, recombinant baculovirus CP08 and Ingelvac CircoFLEX®, were assessed in a modern fattening farm in Xiangyang city. Results: The results indicated no detection of viral antigens in sows; however, weaned piglets and fattening pigs presented high positivity rates, with 8-week-old nursery pigs identified as the peak period for infection. Both vaccines significantly improved average weight gain and reduced antigen positivity, with Ingelvac CircoFLEX® demonstrating superior viral control and economic returns. Conclusions: This study offers valuable scientific and practical guidance for PCV2 control strategies and vaccine selection in Hubei and comparable regions.

Many apicomplexan parasites harbor a non-photosynthetic plastid called the apicoplast, which hosts important metabolic pathways like the methylerythritol 4-phosphate (MEP) pathway that synthesizes isoprenoid precursors. Yet many details in apicoplast metabolism are not well understood. In this study, we examined the physiological roles of four glycolytic enzymes in the apicoplast of Toxoplasma gondii . Many glycolytic enzymes in T . gondii have two or more isoforms. Endogenous tagging each of these enzymes found that four of them were localized to the apicoplast, including pyruvate kinase2 (PYK2), phosphoglycerate kinase 2 (PGK2), triosephosphate isomerase 2 (TPI2) and phosphoglyceraldehyde dehydrogenase 2 (GAPDH2). The ATP generating enzymes PYK2 and PGK2 were thought to be the main energy source of the apicoplast. Surprisingly, deleting PYK2 and PGK2 individually or simultaneously did not cause major defects on parasite growth or virulence. In contrast, TPI2 and GAPDH2 are critical for tachyzoite proliferation. Conditional depletion of TPI2 caused significant reduction in the levels of MEP pathway intermediates and led to parasite growth arrest. Reconstitution of another isoprenoid precursor synthesis pathway called the mevalonate pathway in the TPI2 depletion mutant partially rescued its growth defects. Similarly, knocking down the GAPDH2 enzyme that produces NADPH also reduced isoprenoid precursor synthesis through the MEP pathway and inhibited parasite proliferation. In addition, it reduced de novo fatty acid synthesis in the apicoplast. Together, these data suggest a model that the apicoplast dwelling TPI2 provides carbon source for the synthesis of isoprenoid precursor, whereas GAPDH2 supplies reducing power for pathways like MEP, fatty acid synthesis and ferredoxin redox system in T . gondii . As such, both enzymes are critical for parasite growth and serve as potential targets for anti-toxoplasmic intervention designs. On the other hand, the dispensability of PYK2 and PGK2 suggest additional sources for energy in the apicoplast, which deserves further investigation.

The Triglyceride-glucose (TyG) index is a marker for insulin resistance and metabolic syndrome, while Helicobacter pylori is linked to gastrointestinal diseases and may affect metabolic risks. This study examined the association between the TyG index and H. pylori infection in adults. Data from 3797 participants in the NHANES 1999-2000 cycle were analyzed. The relationship between the TyG index and H. pylori infection was assessed using multivariate logistic regression and a two-piecewise logistic model to explore non-linear effects. Subgroup analyses were conducted based on age, sex, glucose levels, BMI, and CKD. A linear association between the TyG index and H. pylori infection was found. Subgroup analyses revealed significant interactions with a few variables. This study indicates a linear relationship between the TyG index and H. pylori infection, suggesting metabolic influences on H. pylori infection and potential for targeted interventions in at-risk groups.

Toxoplasma gondii ( T. gondii ) is an obligate intracellular parasite that can infect almost all warm-blooded animals, causing serious public health problems. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification (PTM), which is first identified on histones and has been proved relevant to procreation regulation, transcription activation, and cell signaling pathway. However, the biological functions of histone crotonylation have not yet been reported in macrophages infected with T. gondii . As a result, a total of 1,286 Kcr sites distributed in 414 proteins were identified and quantified, demonstrating the existence of crotonylation in porcine alveolar macrophages. According to our results, identified histones were overall downregulated. HDAC2, a histone decrotonylase, was found to be significantly increased, which might be the executor of histone Kcr after parasite infection. In addition, T. gondii infection inhibited the crotonylation of H2B on K12, contributing on the suppression of epigenetic regulation and NF- κ B activation. Nevertheless, the reduction of histone crotonylation induced by parasite infection could promote macrophage proliferation via activating PI3K/Akt signaling pathway. The present findings point to a comprehensive understanding of the biological functions of histone crotonylation in porcine alveolar macrophages, thereby providing a certain research basis for the mechanism research on the immune response of host cells against T. gondii infection.

Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine extracted from ginseng, is widely used to cure many inflammation-related diseases. However, the specific molecular mechanism of the effects of ginsenoside Rg3 on inflammation has rarely been reported. Thus, we established a mouse model of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT) mice, we found that ginsenoside Rg3 treatment significantly mitigated pathological damages and reduced myeloperoxidase (MPO) activity as well as the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); furthermore, the production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), polarization of M2 macrophages and expression levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K), protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR) and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no significant differences with regards to the pathological damage, MPO levels, inflammatory cytokine levels, and protein expression levels of the phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and ginsenoside Rg3 group in MerTK mice. Taken together, the present study demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing the levels of pro-inflammatory mediators and increasing the production of anti-inflammatory cytokines. These processes were mediated through MerTK-dependent activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3.