1.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
2.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
3.Comparison of Wild and Cultivated Alpiniae Oxyphyllae Fructus Based on Traditional Quality Evaluation
Fengfan WANG ; Yajie XIANG ; Jian FENG ; Wencheng HOU ; Wenlan LI ; Yangyang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):235-244
ObjectiveTo compare the differences between wild Alpiniae Oxyphyllae Fructus(WAOF) and cultivated Alpiniae Oxyphyllae Fructus(CAOF) through a traditional quality evaluation system for medicinal materials. MethodsA total of 10 batches of WAOF and 12 batches of CAOF samples were collected from various regions of Hainan province. Relevant analytical methods from the 2020 edition of the Pharmacopoeia of the People's Republic of China were employed to observe the characteristics of WAOF and CAOF, followed by microscopic identification, thin-layer chromatography(TLC) identification, moisture content(toluene method), total ash, acid-insoluble ash, water-soluble and alcohol-soluble extracts(hot dipping method), water-soluble protein, total polysaccharides and total flavonoids(ultraviolet spectrophotometry), and volatile oil content(method A under general rule 2204). The contents of five active components(protocatechuic acid, chrysin, kaempferol, tectochrysin and nootkatone) were quantified using ultra-performance liquid chromatography(UPLC), and the antioxidant activity was evaluated. Building upon traditional quality evaluation of AOF, quantitative measurements were conducted on its appearance traits including diameter, length, plumpness(diameter/length ratio), and color. Canonical correlation analysis was performed using SPSS 26.0 to explore relationships between appearance traits and intrinsic quality. ResultsNo significant differences were observed between WAOF and CAOF in microscopic observation, TLC identification, moisture content, protocatechuic acid content, kaempferol content, odor, or antioxidant activity measured by 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) method. WAOF exhibited significantly higher levels in water-soluble extracts, alcohol-soluble extracts, total polysaccharide content, water-soluble protein content, 100-grain weight, length, and total color difference(ΔE*ab) compared to CAOF(P<0.01). In contrast, CAOF showed significantly higher levels of total ash, acid-insoluble ash, content of total flavonoids, volatile oil content, chrysin content, tectochrysin content, nootkatone content, diameter, plumpness, lightness(L*), red-green chromaticity(a*), yellow-blue chromaticity(b*), and antioxidant activity measured by 1,1-diphenyl-2-picrylhydrazyl(DPPH) method compared to WAOF(P<0.01). Correlation analysis between 7 phenotypic traits and 8 quality traits revealed that among the phenotypic traits, plumpness, L*, a*, and b* exerted significant influence on intrinsic quality. Among the quality traits, total flavonoids, volatile oils, nootkatone, chrysin, and tectochrysin contributed substantially to intrinsic quality. ConclusionPlumpness, L*, a*, and b* of AOF significantly influence its intrinsic quality, and higher values of these parameters indicate relatively superior intrinsic quality. The comprehensive quality evaluation reveals that CAOF samples collected in this study are superior to their wild counterparts.
4.Umbrella decision-making model for diagnosis and treatment of elderly lung cancer patients: Construction and practice
Lunxu LIU ; Jian ZHOU ; Xiang DING ; Nan CHEN ; Jianxin XUE ; Xuelei MA ; Ye WANG ; Weiya WANG ; Liqing PENG ; Xin YOU ; Minggang SU ; Xu CHENG ; Jiao WANG ; Ning GE ; Deying KANG ; Yuchen HUANG ; Jinghan WANG ; Yu TONG ; Yaoxi ZHANG ; Jirong YUE ; Hu LIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):833-839
With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.
5.Clinical features and multimodal quantitative radiological features of primary liver cancer patients with different traditional Chinese medicine syndrome types
Feng WU ; Muqing LUO ; Wantingting WEN ; Ziwei CAI ; Yinqi LIU ; Jian XIANG ; Xiaona ZHOU ; Qian GUO ; Kun ZHANG
Journal of Clinical Hepatology 2026;42(5):1093-1100
ObjectiveTo investigate the association of the traditional Chinese medicine (TCM) syndrome types of primary liver cancer (PLC) with clinical features and multimodal quantitative radiological features on computed tomography (CT) and magnetic resonance imaging (MRI), and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025, and according to the TCM syndrome type, they were divided into stagnation of liver Qi group with 40 patients, stagnation of liver Qi and spleen deficiency group with 109 patients, Qi stagnation and blood stasis group with 62 patients, dampness-heat toxin amassment group with 81 patients, and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s multiple test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups, and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging (CNLC), Child-Pugh class, alanine aminotransferase, aspartate aminotransferase, albumin, direct bilirubin, total bilirubin, prothrombin time, neutrophil, and albumin-bilirubin score (all P<0.05). In the stagnation of liver Qi group, the patients with Child-Pugh class A accounted for 75.00%; among the patients with CNLC stage I PLC, the patients with stagnation of liver Qi accounted for 60.00%, and those with Qi stagnation and blood stasis syndrome accounted for 59.68%, while among the patients with CNLC stage IV PLC, the distribution proportion of dampness-heat toxin amassment (27.16%) and liver-kidney Yin deficiency (30.00%) was significantly higher than that of stagnation of liver Qi (2.50%) (all P<0.05). Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors, ascites, venous tumor thrombus, maximum tumor diameter, intrahepatic metastasis, and lymph node metastasis in the hepatic hilar and retroperitoneal regions (all P<0.05). Compared with the patients with stagnation of liver Qi, the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis; the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions; the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors; the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites (all P<0.05). Compared with the patients with Qi stagnation and blood stasis syndrome, the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus (both P<0.05). Furthermore, among the 184 patients with MRI diffusion-weighted imaging sequences, the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi (all P<0.05). ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types, among whom the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, and liver-kidney Yin deficiency tend to exhibit progressive radiological features, and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.
6.Craniocerebral penetrating injury caused by nail shooting:one case report
Jiang-hao LI ; Zi-xuan WANG ; Xue-lin CHEN ; Xiang-lu LIU ; Jian DING
Fudan University Journal of Medical Sciences 2025;52(5):759-764
We reported the clinical,imaging,and treatment process of a patient with severe cranial penetrating injury caused by a nail from a nail gun that accidentally shot into the eye and penetrated into the skull while working.The patient was admitted to the Qingpu Branch of Zhongshan Hospital,Fudan University after being injured by the nail gun.The patient was admitted to the hospital 1 hour after injury with coma.After admission,the foreign body was completely removed and part of the hematoma was cleared through emergency surgery.After surgery,there were high-risk complications such as cerebral edema peak,intracranial hypertension,intracranial infection,cerebrospinal fluid leakage,and intracranial pseudoaneurysm.The patient eventually regained consciousness and was transferred to rehabilitation treatment.
7.Correlation between triglyceride glucose index and prognosis in elderly patients with unstable angina
Xiang ZHOU ; Ruihan LIU ; Yutong LIU ; Fan TIAN ; Jie ZHANG ; Xiaomao WANG ; Jian CAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):136-139
Objective To explore the correlation between triglyceride glucose(TyG)index and per-cutaneous coronary intervention(PCI)following drug treatment in elderly patients with unstable angina pectoris(UAP).Methods A total of 221 elderly UAP patients admitted to the Hyperbaric Oxygen Department of the First Medical Center of Chinese PLA General Hospital from March 2016 to March 2024 were enrolled,and based on the tertiles of the TyG index,they were divided into low,medium and high TyG index groups(the index:≤8.48,8.49-8.92,>8.92;with 74,74 and 73 cases,respectively).Clinical data of all patients were collected,and whether undergoing PCI after discharge was defined as the endpoint event.The follow-up ended on May 10,2024.The clini-cal data were compared in the three groups.Kaplan-Meier survival curves were plotted to compare the survival rates among the groups,and Cox proportional hazards regression model was em-ployed to analyze the influencing factors for occurrence of endpoint event.Results There were significant differences in the three groups in terms of TyG index,BMI,diabetes,FPG,TC,TG,LDL-C,HDL-C,HbA1c,NT-proBNP,and incidence of endpoint event(P<0.05,P<0.01).Univa-riate Cox proportional hazards regression analysis showed that the TyG index,diabetes,and HbA1c were risk factors for endpoint events in elderly patients with UAP(HR=2.523,95%CI:1.593-3.996;HR=2.543,95%CI:1.263-5.118;HR=1.434,95%CI:1.159-1.774).Further multivariate Cox proportional hazards regression analysis showed that,after adjusting for diabetes and HbA1c,the TyG index was an independent risk factor for PCI after discharge in UAP patients(HR=2.023,95%CI:1.209-3.384).Conclusion In elderly UAP patients receiving drug treat-ment,a high TyG index is positively correlated with undergoing PCI after discharge,and the index is an independent risk factor for PCI in them.
8.MRI subtraction technique for evaluating efficacy of systemic therapy for advanced hepatocellular carcinoma and predicting prognosis after combining with surgery
Tao XIANG ; Bing YUAN ; Xiaohui LI ; Jinghui DONG ; Zhenyu ZHU ; Dingkun LIU ; Jian YANG ; Danni AI ; Jiangtao LIU ; Feng DUAN
Chinese Journal of Interventional Imaging and Therapy 2025;22(3):210-215
Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P<0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST<0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P<0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.
9.Correlation between intrinsic capacity and triglyceride-glucose index in older adults from a Chinese community
Ruihan LIU ; Yutong LIU ; Xiang ZHOU ; Xiaomao WANG ; Jie ZHANG ; Fan TIAN ; Jian CAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):445-449
Objective To investigate the relationship of TyG index and IC.Methods A cross-sectional study was conducted with 1000 older adults living in Wanshou Road Community from May to December 2023.Finally 820 participants were enrolled,and based on the TyG index,they were divided into lower TyG index group(≤7.349,404 cases)and higher TyG index group(>7.349,416 cases).After PSM,there were only 522 participants subjected,including 261 individuals in the lower TyG index group 1 (≤7.349)and 416 ones in the higher TyG index group 2(>7.349).Univariate and multivariate logistic regression analyses were used to assess the correlation between IC and the TyG index as both continuous and categorical variables.PSM was employed to eliminate the confounding effects of covariates to identify the relationship between TyG index and IC in different categories.Results Before PSM,the neutrophil count,WBC count,and Hcy,FPG,TC,TG and HbA1c levels were significantly lower,and lymphocyte count,monocyte count,and AST level were obviously higher in the low TyG index group than the high TyG index group(P<0.05,P<0.01).After PSM,the low TyG index group still had notably lower FPG,TG and HbA1c than the high TyG index group(P<0.05,P<0.01).ROC curve analysis revealed that the cutoff value of TyG index was 7.349.Taking 7.349 as the cutoff value and TyG index as the cate-gorical variable,multivariate logistic regression analysis displayed that TyG index was correlated with IC[OR=3.921,95%CI:2.800-5.491,P=0.001(Model 1);OR=2.744,95%CI:1.739-4.329,P=0.001(Model 2);OR=2.744,95%CI:1.805-4.171,P=0.001(Model 3);OR=2.722,95%CI:1.530-4.843,P=0.001(after PSM)],indicating that TyG index remains an independent risk factor for IC.Conclusion IC is still correlated with TyG index in community-dwelling elderly individuals under different baseline conditions after adjusting for relevant laboratory indicators.As an indicator generated from routine blood test,TyG index has advantages in terms of cost and time.With further validation,TyG may provide a direction for studying IC prediction.
10.Evaluation of antimicrobial activity of milk exosomes loaded with rifamycin S derivative
Zhanqun YANG ; Xiang LI ; Chenghua LIU ; Mengzhu ZHENG ; Shiyong FAN ; Yuchao DONG ; Zihao WANG ; Jian LIN ; Guang YANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2025;39(3):208-215
OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9%.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P<0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

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