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Although biodegradable microplastics are promoted as environmentally safer alternatives to conventional plastics, their long-term biological impacts remain poorly understood. Standard ecotoxicological assessments often rely on physical traits that may mask hidden cellular adjustments and distinct polymer-specific toxicity mechanisms. To address this gap, this study investigated the chronic responses of Daphnia magna to biodegradable polylactic acid (PLA) and conventional polyethylene terephthalate (PET) microplastics by integrating a 21-day life-history assay with global transcriptomic profiling. At the organism level, both PLA and PET exposure reduced somatic growth while leaving reproductive output unaffected, yielding no significant differences between the polymer types. However, transcriptomic analysis revealed that these matching physical outcomes are driven by unique, polymer-dependent molecular patterns. Both treatments showed a coordinated suppression of structural and growth-related pathways alongside the enrichment of regulatory, transport, and protein turnover functions. Yet, PLA induced a broader engagement of stress-responsive functional categories particularly oxidative stress, tetrapyrrole/heme-binding functions, and metabolic control pathways, suggesting a higher regulatory and energetic burden. In contrast, PET elicited a more constrained transcriptomic profile dominated by structural, transport, and RNA-regulatory processes, with minimal activation of redox pathways. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a shared downregulation of ribosome biogenesis under both polymers, but a much stronger enrichment of spliceosome and RNA-regulatory machinery under PET exposure. These findings demonstrate that similar organism-level phenotypes can overlook distinct internal metabolic costs. Consequently, evaluating alternative materials purely by physical symptoms can misrepresent their actual biological impact, highlighting the importance of using transcriptomic profiling to accurately assess the safety of emerging alternative polymers.

The provincial standard conversion work for traditional Chinese medicine(TCM) formula granules is a crucial initiative to accelerate the industrial development of TCM formula granules and intensify scientific supervision. Currently, in the ongoing provincial standard conversion work of TCM formula granules in some regions, issues such as policy divergences and insufficient coordination have surfaced. By systematically reviewing the progress of standard conversion work, including the policy documents issued by drug regulatory authorities and the number of released trial conversion standards, in five provinces, namely Guangdong, Hebei, Jiangsu, Sichuan and Yunnan, this study conducted a comparative analysis across the dimensions of policy objectives, scope of application, basic procedures, core conversion conditions, requirements for application materials, review mechanisms and publicity details. This aimed to clarify their respective emphasis and differentiated characteristics. It also sorted out the quantity and dynamic trends of conversion standards in these five provinces, summarized the existing problems and development bottlenecks in the current conversion work, and put forward targeted approaches for policy optimization. The analysis of provincial policy differences and regulatory trends revealed the current structural contradictions, including difficulties in inter-provincial standard mutual recognition, constraints on the conversion of local commonly used varieties, poor adaptability in the conversion of varieties(e.g., mineral medicines) whose natural properties render them unsuitable for the preparation of formula granules, and inadequate cross-regional regulatory coordination. Furthermore, policy optimization suggestions were proposed, such as establishing an inter-provincial standard coordination mechanism, prioritizing the promotion of regional conversion and mutual recognition of local characteristic varieties, optimizing the conversion pathways for varieties with natural attributes unsuitable for formula granule production(such as mineral medicines), and deepening exchanges and cooperation among provincial-level regulatory authorities. This study provides a reference for advancing TCM formula granules from the stage of "one province, one standard" to the goal of "consistent quality nationwide", and holds practical significance for promoting the standardized and orderly development of the TCM formula granule industry.

Cancer treatment urgently requires individualized and precise strategies, and the development of highly selective drugs targeting specific molecular targets has become the core direction of current research. This study focused on the antitumor activity of the flavonoid compound cudratricusxanthone E(CAS 740810-46-2, C7), finding that it can significantly inhibit the proliferation of human cervical cancer HeLa cells in a time-dependent manner. Through the intervention of different cell death inhibitors, this study preliminarily revealed the potential pathway by which C7 induced cell death. The experiments found that the autophagy inhibitor chloroquine effectively blocked C7-mediated cell death, whereas the apoptosis inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone(Z-VAD-FMK) and the necroptosis inhibitor necrostatin-1(Nec-1) showed no significant effect. This suggested that C7 primarily induced cell death by activating the autophagy pathway, rather than through apoptosis or necroptosis, providing a key clue for understanding the compound's mechanism of action. To further elucidate its molecular mechanism, the study combined network pharmacology predictions with dual-luciferase reporter gene assays, identifying for the first time that the retinoid X receptor α(RXRα) was the target of C7. RXRα is a key regulatory factor in the nuclear receptor family, playing multiple roles in cell proliferation, differentiation, and metabolic regulation. In recent years, it has also been found to have regulatory significance in certain tumor processes. Subsequent experiments confirmed that C7 specifically bound to RXRα, triggering the phosphorylation of downstream adenosine monophosphate-activated protein kinase(AMPK). The activation of AMPK, as a central hub in cellular energy homeostasis and autophagy initiation, significantly promoted autophagic flux. Therefore, C7 drove autophagic cell death in HeLa cells by activating the RXRα/AMPK signaling axis, thereby exerting its antitumor effects. In summary, this study systematically elucidates the novel mechanism by which C7 induces tumor cell death, revealing the complete signaling pathway from the compound targeting RXRα to AMPK activation and ultimately leading to autophagic cell death.

NADPH oxidase, a key enzyme responsible for reactive oxygen species (ROS) production in plants, plays a central role in regulating plant growth and development as well as the transmission of stress signals. However, the regulatory mechanism of ROS mediated by NADPH oxidase in Brassica napus remains unclear. In this study, B. napus 16NTS309 was used as the experimental material, and NADPH oxidase-specific inhibitor (diphenyleneiodonium chloride, DPI) was applied to treat seeds, seedlings, and callus tissues respectively. Combined with nitroblue tetrazolium (NBT) staining, tissue section observation, and superoxide anion (O2-) content determination, the mechanism by which NADPH oxidase-mediated ROS (O2-) regulates seed germination, cell division, and cold stress signal transmission in B. napus was systematically investigated. The results showed that: (1) DPI treatment completely inhibited seed germination (germination rate = 0%), while exogenous application of 0.6% H₂O₂ significantly alleviated this inhibitory effect. Specifically, the seed germination rate, ROS (O2-) content and NADPH oxidase activity increased to 68.34%, 18.52 nmol/g and 423.01 U/g, respectively, which were significantly higher than those in the DPI treatment group. This confirms that NADPH oxidase-mediated ROS plays an important role in seed germination of B. napus; (2) Under normal growth conditions, ROS (O2-) mainly accumulated in the root tip meristem and the edge of the rapidly dividing region of callus tissues. After DPI treatment, the ROS (O₂⁻) signals in root tissues and callus cells were significantly reduced, indicating that NADPH oxidase-mediated ROS signals are involved in regulating the cell division process of B. napus; (3) After cold stress treatment, ROS (O2-) signals in B. napus seedlings and callus tissues burst significantly, with contents of 152.42 nmol/g and 512.61 nmol/g, respectively. In contrast, ROS (O2-) levels and NADPH oxidase activity decreased significantly under the combined treatment of cold stress and DPI, confirming that the massive production of ROS under cold stress is closely associated with NADPH oxidase. This study clarifies the key role of NADPH oxidase-mediated ROS in seed germination, cell division, and cold stress response of B. napus, providing an important theoretical basis and technical support for the genetic improvement of cold-tolerant B. napus varieties and the in-depth study of plant ROS signal regulatory mechanisms.

Hypoxia is a major environmental stressor that threatens fish health in intensive aquaculture, particularly when it co-occurs with bacterial infection. To clarify how hypoxia influences host responses to Aeromonas hydrophila, we established a combined stress model in grass carp using hypoxia (2.0 mg L-1 dissolved oxygen) and bacterial challenge. Survival, hepatic bacterial load, histopathology, hematological indices, antioxidant and immune enzyme activities, and the expression of hypoxia- and immune-related genes were evaluated systematically. The median lethal dose (LD50) of A. hydrophila was 2.41 × 108 CFU mL-1. Compared with normoxic infection, hypoxia markedly worsened disease outcome, as shown by a higher hepatic bacterial burden and more severe lesions in the gill and liver. Combined stress also reduced the proportions of neutrophils and monocytes, suggesting impaired cellular defense. In parallel, SOD, CAT, and GSH-PX activities increased, whereas ACP and LZM activities declined, together with elevated MDA levels, indicating pronounced oxidative stress and weakened innate immune function. Gene-expression analysis showed that hypoxia altered both oxygen-sensing and immune signaling pathways. In the liver, hif-1α expression was markedly induced under hypoxic conditions, whereas inflammatory cytokines, especially il-6 and il-10, were strongly upregulated. Notably, hepcidin expression was significantly increased and showed a pattern consistent with the induction of il-6, suggesting a potential association with the IL-6-hepcidin regulatory pathway under combined stress. However, this response may represent a compensatory mechanism that is insufficient to counteract the overall impairment of immune defense under hypoxic conditions.Overall, hypoxia enhanced the pathogenic effects of A. hydrophila by intensifying oxidative stress, impairing immune defense, and altering immune and antimicrobial regulatory responses. These findings improve our understanding of the interaction between environmental hypoxia and bacterial infection in grass carp and provide a basis for disease prevention in aquaculture.

This study aimed to explore the mechanisms of Buyang Huanwu Decoction(BYHWD) and its different fractions in treating hyperlipidemia, screen lipid-regulating active components, and optimize the formula ratio. Metabolites in drug-containing sera were identified. A total of 96 ICR mice were randomly divided into a blank group(12 mice) and a modeling group(84 mice). The modeling group was fed a high-fat diet for 6 weeks to establish a hyperlipidemia model, and then randomly divided into a model group, an atorvastatin group(2.600 mg·kg~(-1)), a BYHWD group(18.571 g·kg~(-1)), an alcohol precipitation group(1.496 g·kg~(-1)), a 30% fraction group(0.163 g·kg~(-1)), a 50% fraction group(0.113 g·kg~(-1)), and a 90% fraction group(0.060 g·kg~(-1)). Samples were collected after administration for three weeks. Serum lipid indices, hepatic cholesterol(CHO), triglyceride(TG), and total bile acid(TBA) levels were detected. Pathological changes in the liver and adipose tissue, as well as the mRNA and protein expression of lipid-related genes(sterol regulatory element-binding protein 2 [SREBP2], insulin-induced gene 1 protein [INSIG-1], 3-hydroxy-3-methylglutaryl-CoA reductase [HMGCR], liver X receptor alpha [LXRα], ATP-binding cassette transporter A1 [ABCA1], and cytochrome P450 family 7 subfamily A member 1 [CYP7A1]) in the liver, were also determined. The results showed that the alcohol precipitation and 30% fraction showed significant effects on lowering CHO, and the alcohol precipitation and 50% fraction exhibited better regulatory effects on white adipose tissue. Except for the 90% fraction, all the other had reduced hepatic CHO and TG levels. All groups showed an impact on TBA. BYHWD and its different fractions could regulate the expression of lipid-related genes and proteins in the liver. In conclusion, the BYHWD, alcohol precipitation, 30% fraction, and 50% fraction effectively treat hyperlipidemia by reducing hepatic CHO, but their mechanisms of action are different: the 50% fraction mainly inhibits CHO synthesis; the alcohol precipitation and 30% fraction focus on promoting CHO efflux; the alcohol precipitation has significant advantages in CHO conversion to bile acids.

This study investigated the effects and potential mechanisms of hesperetin(HST) in targeting mitochondria to regulate hepatocyte pyroptosis and alleviate alcoholic liver injury through in vitro experiments. Human immortalized hepatocytes(THLE-2) were used to establish an in vitro alcoholic liver injury model induced by 200 mmol·L~(-1) ethanol. The effective concentrations of HST(40, 80, and 160 μmol·L~(-1)) were determined using the MTT assay. The effects of HST on hepatocyte pyroptosis were evaluated by optical microscopy, lactate dehydrogenase(LDH) release assay, and flow cytometry, and its effects on lipid accumulation were assessed using Nile red staining and cholesterol and triglyceride assay kits. Further intervention with a high dose of HST was performed, and the expression levels of pyroptosis-related molecules, including caspase-1, gasdermin D(GSDMD), interleukin-18(IL-18), and interleukin-1β(IL-1β), were detected by Western blot and PCR. In addition, a caspase-1 inhibitor(Z-YVAD-FMK) was used to reversely validate the regulatory effect of HST on the classical pyroptosis pathway. The morphology of the endoplasmic reticulum, lysosomes, and mitochondria was observed using confocal laser scanning microscopy. Superoxide dismutase(SOD) levels were measured using a commercial assay kit, mitochondrial membrane potential was analyzed by flow cytometry, and the gene expression levels of mitochondrial membrane transport proteins, including voltage-dependent anion channel 1(VDAC1), voltage-dependent anion channel 2(VDAC2), translocase of the outer mitochondrial membrane 20(TOM20), and translocase of the outer mitochondrial membrane 34(TOM34), were determined by PCR. Meanwhile, the mitochondrial reactive oxygen species(mtROS) inducer rotenone was employed to validate the mitochondria-targeted regulatory effects of HST on mitochondrial function. The experimental results showed that HST concentration-dependently increased hepatocyte viability, reduced LDH levels, significantly alleviated hepatocyte pyroptosis, and improved lipid accumulation, while downregulating the expression of caspase-1, GSDMD, IL-18, and IL-1β. After the addition of a caspase-1 inhibitor, the inhibitory effect of HST on hepatocyte pyroptosis was further confirmed. Mechanistic investigations revealed that HST targeted mitochondria by scavenging mtROS, upregulating SOD expression, restoring mitochondrial membrane potential, and downregulating the expression of mitochondrial membrane-associated transport proteins VDAC1, VDAC2, TOM20, and TOM34. Furthermore, the addition of the mtROS inducer rotenone reversely validated the role of HST in alleviating hepatocyte pyroptosis through mitochondrial targeting. In summary, HST alleviates hepatocyte pyroptosis and improves lipid metabolism disorders by targeting mitochondria and regulating the classical pyroptosis pathway, thereby mitigating alcoholic liver injury. These findings provide a theoretical basis for the potential clinical application of HST in the treatment of alcoholic liver injury.

Red-eared slider turtles (Trachemys scripta elegans) possess exceptional tolerance to prolonged periods of anoxia, surviving seasonally in oxygen-deprived environments without apparent cardiac damage. This resilience is supported by deep metabolic suppression and transcriptional reprogramming, but the contribution of microRNA in post-transcriptional gene regulatory control remains poorly understood. Here, we employed small RNA sequencing to profile cardiac miRNA expression under normoxic and anoxic conditions. Differential expression analysis of 26 human-conserved miRNAs reveal upward trends in miR-1973 (p = 0.003) and miR-6747-5p (p = 0.011) in response to 20 hours of anoxia at 5 &#xb0;C. Predicted gene set enrichment analysis suggest roles for miRNA in diverse protein post-translational modification, cytoskeletal remodeling and metabolic adaptation through suppression of the ribosome and oxygen-dependent activities. Separately, 35 non-human miRNAs mapped to Chrysemys picta turtles revealed an additional four (cpi-miR-2188-5p, cpi-miR-15b-5p, cpi-miR-551-5p, cpi-miR-1805-3p) that were anoxia-responsive (|FC| > 1.5, FDR-adjusted p < 0.05). These results provide evidence that miRNAs may contribute to cardiac plasticity in T.s. elegans by modifying the cellular phenotype and reducing energy expenditure during anoxia. Our study proposes novel insights into the post-transcriptional control of vertebrate anoxia tolerance and highlights potential regulatory motifs relevant to ischemia-reperfusion medicine.

This study uses a rat model of middle cerebral artery occlusion and reperfusion(MCAO/R) to investigate the mechanism by which Xinglou Chengqi Decoction treats cerebral ischemia-reperfusion injury, employing metabolomics and metagenomics approaches. A rat model of MCAO/R was established to evaluate the neurological function and modified neurological severity scores. Then, the brain tissue pathology, inflammatory mediators, oxidative stress, blood-brain barrier integrity, cerebral edema, and intestinal barrier function were examined to assess the pharmacological effects of Xinglou Chengqi Decoction. Metabolomics analysis of the brain tissue and metagenomics analysis of the intestinal contents were conducted to investigate the metabolism and gut microbiota regulatory mechanisms of Xinglou Chengqi Decoction. The results suggested that Xingluo Chengqi Decoction improved the neural function, reduced the severity of cerebral infarction, attenuated oxidative stress and inflammatory factor levels, boosted blood-brain barrier factor levels, minimized cerebral edema, and strengthened intestinal mucosal barrier protection, thus treating cerebral ischemia-reperfusion injury in rats. Metabolomic analysis of the brain tissue revealed that Xinglou Chengqi Decoction primarily treated ischemic stroke through 14 potential metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, valine, leucine, and isoleucine biosynthesis, and phenylalanine metabolism. Metagenomic analysis revealed that administration of Xinglou Chengqi Decoction increased the relative abundance of Firmicutes, Clostridia and Bacilli, Clostridiales and Lactobacillales, and Lachnospiraceae and Oscillospiraceae. In addition, it influenced the biosynthesis of aminoacyl-tRNA, valine, leucine, and isoleucine, along with peptidoglycan synthesis, thereby enhancing the regulatory function of the gut microbiota. Simultaneously, Xinglou Chengqi Decoction exerts therapeutic effects through the gut-brain crosstalk mediated by substances such as amino acids and fatty acids, which act within the biosynthetic and metabolic pathways.

This study adopted an integrated strategy combining serum transitional component screening, network pharmacology prediction, and animal experiment verification to systematically explore the core active components and mechanism of action of Yinxing Yangnao Formula(YYF) in the treatment of vascular dementia(VD), aiming to provide solid experimental evidence for the modernization of this classical TCM prescription. With the use of ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS), a total of 97 chemical components were identified from the YYF extract by combining accurate mass-to-charge ratio, characteristic fragmentation ions of MS/MS, comparison with reference standards, and matching with literature databases. Furthermore, 27 serum transitional components were captured through the analysis of YYF-containing serum from rats, which were inferred as the key material basis for the in vivo pharmacodynamic effects of YYF. The potential targets of the serum transitional components were predicted using the SwissTargetPrediction database, and VD-related disease targets were screened from authoritative databases including GeneCard, OMIM, and GEO with the keyword dementia vascular. A total of 275 common targets were obtained with the Jvenn online tool. The "drug-component-target-disease" network was constructed using Cytoscape 3.9.1 software, and core active components such as isoscopoletin, jaceosidin, catalpol, senkyunolide F, and bilobalide were screened out. The protein-protein interaction(PPI) network was constructed via the STRING database, identifying key regulatory targets including the phosphatidylinositol 3-kinase family, sarcoma, protein tyrosine phosphatase, non-receptor type 11, Janus kinase 2, and protein tyrosine kinase 2. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis revealed that the core targets were mainly enriched in biological processes such as oxidative stress, neurological function, and immune and inflammatory responses, involving phosphoinositide 3-kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3) signaling pathways. Molecular docking results showed that bilobalide had a good binding effect with core targets. Verification experiments on VD rat models demonstrated that YYF might exert the therapeutic effect by alleviating oxidative stress through modulating the serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and malondialdehyde(MDA). This study preliminarily clarified the material basis, pharmacological effects, and underlying mechanism of YYF in the treatment of VD, providing a direction and basis for subsequent research on the complete regulatory chain of "drug-target-pathway-phenotype".

This study uncovered potential regulatory networks associated with cleistogamy in pigeonpea by analyzing interactions between lncRNAs, mRNAs, and miRNAs. Cleistogamy, a unique floral adaptation, is a valuable trait offering a unique reproductive advantage in self-pollinated species. In crops like pigeonpea, outcrossing significantly contributes to the deterioration of varietal purity, impacting the overall seed purity. Thus, as a primary effort to get molecular insights governing cleistogamy in pigeonpea, we performed RNA-seq analysis of unopened flower buds from three pigeonpea genotypes having different flower morphologies i.e., ICPL87154 (cleistogamous), ICPL87119 (chasmogamous), and UP26 (partially wrapped petals). Comparative analysis revealed differential gene expression patterns in the cleistogamous vs. chasmogamous combination. Comparative transcriptome profiling identified differential enrichment of biological pathways between the genotypes. Relative to the non-cleistogamous genotype, the cleistogamous genotype exhibited increased expression of genes involved in carbohydrate metabolism and ubiquitin-mediated proteolysis, whereas genes associated with hormone signaling and endocytosis showed reduced expression. To further delineate the regulation, LncRNAs were predicted from the assembled transcriptome, and a total of 25,307 transcripts were identified as lncRNAs based on length, exon number, and coding potential. Further interaction analysis revealed regulatory lncRNA-miRNA-mRNA networks, and expression validation of key networks uncovered some candidate genes, such as FT-interacting protein 1 (FTIP1) and auxin response factor 2A, that can be potentially involved in this trait. Upregulation of miRNAs miR156b, miR169g, and miR171g in the cleistogamous genotype suggests the post-transcriptional regulation of cleistogamy. Additionally, simple sequence repeats (SSRs) identified in differentially expressed genes and lncRNAs offer additional genomic resources pertaining to this trait. This study provides the first comprehensive identification of DEGs and DE-lncRNAs associated with cleistogamy in pigeonpea, laying the groundwork for further molecular dissection.

Bone is a primary site for lung cancer metastasis, and T-box transcription factor 15 (Tbx15) is aberrantly expressed in multiple cancers. It aims to investigate the role of Tbx15 in lung cancer bone metastasis and its potential mechanisms. TCGA and cellular analyses revealed elevated Tbx15 lung adenocarcinoma tissues and cells (MLE-12, CMT64, LA795, LLC), while recombinant IL-25 (rIL-25) expression was low in supernatants and lysates. And Pearson analysis showed a negative correlation between Tbx15 and IL-25. The CCK-8 and EdU assays showed that Tbx15 knockdown inhibited LA795 cell proliferation, migration, and invasion. In vivo, simultaneous Tbx15 knockdown and rIL-25 administration promote tumor cell growth and accelerate bone metastasis in mice. Mechanistically, Tbx15 knockdown upregulates IL-25 expression, thereby promoting apoptosis of osteoclasts (OCs) and suppressing bone metastasis. Besides, OCs were treated with rIL-25 and the apoptosis inhibitor Z-VAD-FMK, and found that extracellular IL-25 protein promoted apoptosis of OCs by upregulating major vault protein (MVP) expression. In conclusion, our study demonstrates that knockdown of Tbx15 upregulates IL-25 expression to promote apoptosis of OCs, while exogenous supplementation of IL-25 promotes proliferation and bone metastasis of lung adenocarcinoma cells. The dual role of IL-25 in Tbx15-positive lung adenocarcinoma cells and its potential regulatory mechanism were elucidated.

To investigate the effects of Plantaginis Semen(PS) and its salt-processed product on D-galactose(D-gal)-induced aging in mice and elucidate the underlying mechanism based on the adenosine monophosphate-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/nuclear factor-kappa B(NF-&#x3ba;B) pathway, and clarify the mechanism of action by which PS and its salt-processed product in delaying aging. A total of 48 mice were randomly divided into the blank control group, model group, low-, medium-, and high-dose PS groups(0.9, 1.8, 3.6 g&#xb7;kg~(-1)), and low-, medium-, and high-dose salt-processed PS groups(at the same doses as the PS groups). Except for the blank control group, all groups were subcutaneously injected with D-gal on the nape and back to establish an aging model, which lasted for 60 consecutive days. Starting from the 30th day of modeling, the PS group and the salt-processed PS groups received corresponding drug interventions by gavage for 30 consecutive days, while the blank control group and model group received an equal volume of distilled water using the same method. During the administration period, cognitive function was assessed using the nest-building score and the Morris water maze test. Subsequently, mouse tissue were collected under anesthesia to calculate the organ indices of the kidneys and liver. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of renal tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in renal tissue. Real-time quantitative polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression levels of aging-related genes, including AMPK and SIRT1. Western blot was used to detect the protein expression levels of the aging markers AMPK, SIRT1 and NF-&#x3ba;B. The results showed that compared with the model group, the nesting ability of mice in all dose groups of raw PS and salt-processed PS increased to varying degrees. Notably, the nesting score of the medium-dose salt-processed PS group was significantly higher than that of the medium-dose raw PS group(P<0.05). Compared to the blank control group, the model group had a significantly prolonged escape latency and a significantly decreased frequency of platform crossings(P<0.05). After drug intervention, all treatment groups showed a shortened escape latency and an increased number of platform crossings, indicating improved spatial memory compared to the model group. Compared with the model group, all dose groups of raw and salt-processed PS groups significantly increased the kidney and liver indices of aging mice(P<0.05), with the high-dose salt-processed PS group showing significantly higher kidney and liver indices than the high-dose PS group(P<0.01). Histopathological examination revealed that raw PS and salt-processed PS ameliorated renal tissue morphology, resulting in more intact glomerular structures and regular tubular lumens. Furthermore, both raw PS and salt-processed PS significantly increased the activities of SOD in renal tissue(P<0.05) and decreased the content of MDA(P<0.05). Additionally, they significantly up-regulated the mRNA and protein expression levels of AMPK and SIRT1(P<0.05) while down-regulating the protein expression levels of NF-&#x3ba;B(P<0.05). The regulatory effects on these indices were more pronounced in the salt-processed PS groups(P<0.05). In conclusion, both raw PS and its salt-processed product can significantly delay aging by regulating the AMPK/SIRT1/NF-&#x3ba;B signaling pathway and ameliorating oxidative stress. Furthermore, the anti-aging efficacy is enhanced after processing, with the salt-processed product demonstrating superior effects.

Carcinogenicity evaluation is a critical component of chemical risk assessment, yet traditional in&#xa0;vivo testing remains time consuming, costly, and ethically challenging. Computational approaches based on machine learning offer promising alternatives, but the relative contributions&#xa0;of different molecular representation strategies for predicting in&#xa0;vivo carcinogenicity remain insufficiently explored. This study aimed to systematically evaluate the impact of molecular embeddings, classical descriptors, and toxicophore structural alerts on the performance of machine learning models for predicting in&#xa0;vivo carcinogenicity. A curated dataset of 2090 distinct compounds tested in&#xa0;vivo with rodents was assembled by integrating five major toxicological databases. Compounds were represented using classical molecular descriptors, descriptor sets enriched with structural alerts, SMILES-derived molecular embeddings, and hybrid combinations of these representations. Twenty-four machine learning classifiers were benchmarked under a 10-fold stratified cross-validation protocol. Model performance was assessed using accuracy, precision, recall, F1-score, and AUC-ROC, with statistical significance evaluated using Friedman and Nemenyi tests. Results indicated that representations combining molecular descriptors with structural alerts tend to yield the most consistent predictive performance across models. Embeddings contribute as complementary features but do not replace classical representations. These findings reinforce the central role of chemically interpretable, expert-driven descriptors, particularly those incorporating genotoxic structural alerts, in regulatory-relevant carcinogenicity modeling.

Chlorogenic acid is a key medicinal component of Taraxacum mongolicum. However, the gene family characteristics of its key biosynthetic enzyme, hydroxycinnamoyl CoA: quinate hydroxycinnamoyl transferase(HQT), have not been clearly defined. So far, only two functional HQT genes have been identified in T. antungense and only one in Echinacea purpurea, while the HQT genes of T. mongolicum have not yet been reported. In this study, T. mongolicum was used as the research material to clone the chlorogenic acid biosynthesis genes TmHQT1, TmHQT2, and TmHQT3. The physicochemical properties of the proteins were predicted using tools such as ExPASy ProtParam, SOPMN, and SWISS-MODEL, and prokaryotic expression vectors pET30a-TmHQTs were constructed. Using caffeoyl-CoA and quinic acid as substrates, in vitro enzymatic reaction experiments were conducted to verify the functions of the TmHQTs genes. The results showed that three key chlorogenic acid biosynthetic enzyme genes, TmHQTs, were cloned from T. mongolicum. The catalytic activities of the proteins encoded by the three genes differed significantly: HQT2 catalyzed the production of chlorogenic acid at 1.63 &#x3bc;g&#xb7;mL~(-1), higher than that in the case of HQT1 and HQT3(1.56 and 1.44 &#x3bc;g&#xb7;mL~(-1), respectively). The lower activity of HQT3 was related to its higher protein instability index 45.49. This study is the first to clone three TmHQTs genes with in vitro catalytic function from T. mongolicum, revealing the structure-function differentiation characteristics of the encoded proteins and providing direct evidence for the multi-gene synergistic regulatory mechanism of chlorogenic acid biosynthesis in T. mongolicum.

The development of antimicrobial resistance (AMR) is a major threat to global public health and environmental security. While antibiotics are known drivers, a wide range of non-antibiotic pollutants also promote antibiotic resistance genes (ARG) dissemination, yet the underlying unifying mechanism remains poorly integrated. This paper systematically analyzes how reactive oxygen species (ROS) act as major convergent mediator that drive the evolution of ARGs by promoting mutation and horizontal gene transfer (HGT) under various environmental stress conditions. The mechanisms of antibiotic-induced ROS generation and the controversial role of ROS in bacterial lethality are first delineated. It is then revealed that numerous non-antibiotic stressors, including disinfectants, heavy metals, nanoparticles, pharmaceuticals, and organic pollutants, convergently promote ARG conjugation, transformation, and transduction. Within these processes, moderate levels of intracellular ROS promote ARG dissemination, whereas excessive oxidative stress inhibits transfer or compromises cell viability. Based on these observations, we propose the concept of an "oxidative window" to describe the bidirectional regulatory effect of ROS on ARG dissemination at different concentrations. Furthermore , strategies to suppress ARG spread by modulating intracellular ROS are discussed, shifting from total elimination to precise regulation within the permissive window. Building upon this mechanistic framework, we further discuss the potential of incorporating ROS-related metrics into machine-learning-assisted risk assessment models and evaluate emerging ROS-regulation strategies for mitigating ARG dissemination. By reframing ROS from a passive byproduct into a measurable and potentially predictive indicator of ARG dissemination risk, this review provides a new conceptual basis for predicting and controlling environmental resistance risks.

This article reviews the clinical application of direct injection of stem cells and differentiated cells, comparing established European experience with the rapidly evolving regenerative medicine landscape in Dubai. It highlights the strongest evidence in orthopedic applications, outlines current limitations in standardization and long-term outcomes, and examines emerging technologies such as exosomes and engineered cellular therapies. Differences in regulatory frameworks and clinical adoption are discussed, emphasizing the need for continued evidence-based integration and ethical oversight in the expansion of regenerative medicine.