ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Aim To investigate the effect of angioten-sin Ⅱ type 1a receptor(AT1aR)knockout on cardiac dysfunction in rats with obesity and its possible molecu-lar mechanism.Methods SD rats(n=24)were used to generated the whole-body AT1 aR-deficiency rats by sgRNA and the CRISPR/Cas9 system,and the obesity model was constructed by feeding with high-fat diet(HFD).They were divided into four groups:wildtype(WT)and knockout(KO)groups with nor-mal feeding and their respective high-fat diets groups.Color ultrasound diagnostic instrument was uses to e-valuate the cardiac function;oil red O staining was a-dopted to stain the myocardial lipids;RT-PCR was used to detect the levels of GPX4 and Ptgs2 genes in myocardial tissue.Western blot was employed to detect the expression of GPX4,ferritin,Nrf2,HO-1 and NQO1 in rat myocardial tissue.ELISA and other kits were used to determine the lipid contents in serum and myocardium.Results It was found that high-fat feed-ing caused cardiac dysfunction,serum lipid disorders,oxidative stress and ferroptosis in SD rats.However,these changes were attenuated in AT1aR knockout rats fed with high-fat diet.Furthermore,compared with WT-HFD group,KO-HFD rats showed enhanced acti-vation of the Nrf2/HO-1 pathway in the myocardium,reduced ferroptosis,decreased lipid accumulation,and reduced cardiac dysfunction.Conclusion AT1aR knockout can improve HFD-induced cardiac dysfunc-tion by enhancing antioxidant capacity and reducing the degree of ferroptosis.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.