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”.

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”.

ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

Objective To explore the regulatory role of farnesol in Candida albicans(C.albicans)biofilm cAMP-PKA signaling pathway and its correlation with drug resistance.Methods Standard,fluconazole-resistant,wild and high RAS1 gene expression strains of C.albicans were cultured to different phases of the biofilm(6,12,24,36 h),and the sessile minimal inhibitory concentration 50％(SMIC50)of fluconazole were determined by XTT reduction after farnesol treatment.The regulatory effects of farnesol on the ex-pression of genes related to the cAMP-PKA signaling pathway in standard and fluconazole-resistant strains of C.albicans,such as RAS1,CYR1,PDE2 were examined using qPCR;the effects of farnesol on the protein expression of the pathway were analyzed by Western blot.RAS1 gene expression of the wild and high RAS1 gene expression strains was measured by qPCR.Results ① Compared with the standard strain,resistant strains of C.albicans had higher levels of biofilm SMIC50 at 6,12 and 24 h;there was no significant difference in RAS1 expression(P＞0.05),while CYR1 expression increased significantly at 6 and 24 h in the biofilm(P＜0.01),and PDE2 expression decreased at 6 h in the biofilm(P＜0.01).②After treatment with farnesol,the resistance of the biofilm of the standard strain and drug-resistant strain decreased.Compared with no treatment with farnesol,the expression of RAS1 in the biofilm of the standard strain and drug-resistant strain decreased at all time points(P＜0.01);CYR1 expression decreased in the biofilm at 6,24 and 36 h,and in-creased in the biofilm at 12 h(P＜0.01);PDE2 expression increased in the 12 h biofilm(P＜0.01).③Compared with the wild strain,the high expression strain of RAS1 gene showed higher SMIC50 in the biofilm at 12 and 24 h,and significantly higher expression of RAS1 gene in the biofilm at 12,24 and 36 h(P＜0.01).④After treatment with farnesol,the resistance of wild-type strains and high expres-sion strains of RAS1 gene decreased.Compared with the untreated group,the expression of RAS1 gene in the biofilm of wild-type and RAS1 gene high expression strain decreased at 12 and 24 h(P＜0.01).Conclusion Farnesol can affect the sensitivity of C.albicans biofilm to fluconazole by regulating the expression of resistance molecules RAS1,CYR1 and PDE2 in the cAMP-PKA pathway.The regulatory effect varies at different stages of biofilm formation.

Objective To analyze the global literature related to functional cure of hepatitis B from 2019 to 2023 by using bibliometric analysis methods,so as to help researchers understand the research hotspots and trends in this field.Methods The literature related to the topic of functional cure of hepatitis B included in the Science Citation Index Expanded(SCI-Expanded)of the Web of Science Core Collection from 2019 to 2023 was searched.By using VOSviewer and CiteSpace visual analysis tools,analyses were conducted from the perspectives of publication trends,international research cooperation networks,and keyword emergence,and were elaborated with the specific contents of the related literature to elucidate research hotspots and trends.Results A total of 600 eligible papers in this field were included.Keyword co-occurrence and thematic clustering suggested that the main research directions of functional cure were:serum biomarkers for prediction and monitoring of functional cure,functional cure and immunity,nucleoside analog discontinuation,interferon therapy,and long-term prognosis of functional cure.The research contents of the ESI highly cited original research papers were similar to the clustering of the above,but showed more attention on the novel agents for functional cure.The content of the keyword emergence map showed that hotspots of interest changed from virologic mechanisms and serum markers,to nucleoside analog discontinuation and interferon therapy,and finally to immunologic mechanisms and new drug.Conclusion The research hotspots and trends of functional cure of hepatitis B were focused on virological mechanism,serum markers,immunological mechanism,nucleoside analog discontinuation,interferon therapy,and long-term prognosis after cure.

Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.

Objective To analyze the global literature related to functional cure of hepatitis B from 2019 to 2023 by using bibliometric analysis methods,so as to help researchers understand the research hotspots and trends in this field.Methods The literature related to the topic of functional cure of hepatitis B included in the Science Citation Index Expanded(SCI-Expanded)of the Web of Science Core Collection from 2019 to 2023 was searched.By using VOSviewer and CiteSpace visual analysis tools,analyses were conducted from the perspectives of publication trends,international research cooperation networks,and keyword emergence,and were elaborated with the specific contents of the related literature to elucidate research hotspots and trends.Results A total of 600 eligible papers in this field were included.Keyword co-occurrence and thematic clustering suggested that the main research directions of functional cure were:serum biomarkers for prediction and monitoring of functional cure,functional cure and immunity,nucleoside analog discontinuation,interferon therapy,and long-term prognosis of functional cure.The research contents of the ESI highly cited original research papers were similar to the clustering of the above,but showed more attention on the novel agents for functional cure.The content of the keyword emergence map showed that hotspots of interest changed from virologic mechanisms and serum markers,to nucleoside analog discontinuation and interferon therapy,and finally to immunologic mechanisms and new drug.Conclusion The research hotspots and trends of functional cure of hepatitis B were focused on virological mechanism,serum markers,immunological mechanism,nucleoside analog discontinuation,interferon therapy,and long-term prognosis after cure.

Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.

Objective To design an intelligent airborne soldier physical training system based on human body composition analysis to solve the problems in diversity of training mode,targeted training plan and high incidence of military training-related injuries.Methods The intelligent airborne military physical training system was designed with B/S architecture and developed with Python language,which was composed of four functional modules for airborne soldier information acquisition,trainee physical fitness state assessment,physical fitness training program recommendation and airborne soldier physical fitness training program evaluation.The airborne soldier information acquisition module collected and analyzed the trainee physiological parameter information with a human body composition analyzer,clarified the parameter characteristics related to physical training with considerations on military physical training requirements and constructed a trainee physical fitness assessment parameter model;the trainee physical fitness state assessment module established an evaluation model based on machine learning to realize stage-by-stage physical fitness evaluation for airborne soldiers;the physical fitness training program recommendation module was constructed based on the physical training feature similarity algorithm and graph embedding theory to provide decision making assistance for program development of airborne military physical training;the airborne soldier physical fitness training program evaluation module compared the physical fitness and evaluation results before and after training by means of list and chart,and updated the training program based on the evaluation results by calling the physical training program recommendation module.Results The intelligent airborne soldier physical training system contributed to forming an individualized physical fitness training recommendation mechanism after trainee body evaluation,modifying training program based on comparison and feedback for stage-by-stage training evaluation,so as to decrease the incidence of military training-related injuries while increasing the training efficiency.Conclusion The system developed improves airborne soldier physical training in rationality and reliability,and provides references for intelligent military training of the PLA.[Chinese Medical Equipment Journal,2025,46(2):16-23]