1.Dual Targeting of TBK1 and JAK-STAT1 Pathways by (-)-epigallocatechin-3-gallate Suppresses Type I Interferon-driven Inflammation
Liang LI ; Qi-Huan SHENG ; Huan LIU ; Wen-Hao YANG ; Jia-Lin SHI ; Ying-Jie SUN ; Rui JING ; Wei-Hua MAI ; Zhi-Min LI ; Xiao-Li XIE
Progress in Biochemistry and Biophysics 2026;53(7):1969-1983
ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.
2.Establishment and application of ultra-fast real-time PCR for Brucella detection
Zhen-na XU ; Zhi-peng WU ; Wei-bin HONG ; Zhi-shen GUAN ; Qi-ming LIN ; Zuan-lan MO ; Yi-fei YE ; Hai-yan XIE ; Min LI ; Yan-qiu ZHU ; Xiao-jun LI ; Xian-peng ZHANG
Chinese Journal of Zoonoses 2025;41(3):278-283
This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20%to 0.91%,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100%compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.
3.Predictive value of stress myocardial perfusion imaging with gated SPECT for cardiac death in patients with chronic kidney disease
Ying ZHANG ; Jian JIAO ; Zhi CHANG ; Xu HAN ; Quan LI ; Junqi LI ; Yehong ZHANG ; Xiaofen XIE ; Wei DONG ; Hongzhi MI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):346-351
Objective:To evaluate the clinical predictive value of SPECT myocardial perfusion imaging (MPI) in the occurrence of cardiac death in patients with chronic kidney disease (CKD).Methods:A retrospective follow-up was performed for 160 patients (109 males, 51 females; age: 68.5(61.0, 74.0) years) who underwent MPI in Beijing Anzhen Hospital, Capital Medical University between June 2017 and March 2024. The 17-segment 5-point method was used for image analysis to obtain the left ventricular myocardial perfusion and functional parameters. The patients were followed up for cardiac death, and divided into death group and survival group. Clinical data of those 2 groups were compare by χ2 test, the independent-sample t test or Mann-Whitney U test. Cox proportional hazards regression analysis was used to analyze the predictors related to cardiac death. The ROC curve was used to analyze the performance of predictors. Survival curves were obtained by the Kaplan-Meier method, and log-rank test was performed to compare the difference between 2 groups. Results:The follow-up time of 160 patients with CKD was 26.0(10.0, 46.5) months. Of 160 patients, 17 died and 143 survived. There were statistically significant differences in body mass index (BMI), previous myocardial infarction, previous revascularization, hypersensitive C-reactive protein (hs-CRP), positive MPI, left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) between the death group and the survival group ( χ2 values: 4.58-16.13, t values: -2.34, -3.97, Z values: from -2.81 to 5.02, all P<0.05). Multivariate Cox regression analysis showed that SSS (hazard ratio ( HR)=1.153, 95% CI: 1.062-1.252, P=0.001) and hs-CRP ( HR=1.031, 95% CI: 1.004-1.058, P=0.023) were independent risk factors for cardiac death in patients with CKD. The optimal cut-off value of SSS for predicting cardiac death in those patients was determined to be 8 with the AUC of 0.815, and the incidence of cardiac death in the SSS ≥8 group was significantly higher than that in the SSS<8 group (33.3%(12/36) vs 4.0%(5/124); χ2 = 25.44, P<0.001). Conclusion:MPI is an important imaging method for the evaluation of cardiac death in patients with CKD, SSS and hs-CRP are important risk factors in predicting cardiac death in those patients.
4.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
5.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
6.Quantitative analysis of motion of cardiac substructures in deep inspiratory breath holding radiotherapy for left breast cancer
Zhao-hui TANG ; Zhe ZHANG ; Wei-bin MAO ; Bo HUANG ; Jun-feng AI ; Chao-fan ZHU ; Zhi-chao XIE ; Ya-jie LIU
Chinese Medical Equipment Journal 2025;46(3):54-58
Objective To quantify the volume and movement of cardiac substructures by using coronary computed tomography angiography(CCTA)to provide guidance for the design of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.Methods Totally 18 female patients who received conventional chest plain scan and CCTA were selected to simulate the design process of radiotherapy plan for left breast cancer patients with internal mammary lymph nodes.Retrospective reconstruction of CCTA data was performed for each patient,with 10 phase images(with an interval of 10%)within a R-R cardiac cycle(10%-100%)to simulate the true range of motion of the heart.The heart,left atrium(LA),left ventricle(LV),right atrium(RA),right ventricle(RV),left anterior descending artery(LAD),left circumflex coronary artery(LCX)and right coronary artery(RCA)were contoured at each phase.The distances from the centroid position to the average position of LAD,LCX and RCA were measured at each phase in the superior-inferior(SI),anterior-posterior(AP)and left-right(LR).The average volume and range of volume changes of LA,LV,RA,RV and heart were analyzed within a cardiac cycle.The expansion margins of planning organs at risk volume(PRV)were calculated.SPSS 19.0 software was used for statistical analysis.Results The following average absolute displacements were found in SI,AP and LR coordinates:(1.8±0.7)mm,(1.2±0.5)mm and(1.5±0.5)mm for LAD,respectively;(2.1±0.7)mm,(1.5±0.6)mm and(1.9±0.7)mm for LCX,respectively;(1.6±0.5)mm,(2.2±0.9)mm and(2.2±0.8)mm for RCA,respectively.The volume changes of LA,LV,RA,RV and heart within a cardiac cycle ranged from 34.3 to 63.9 cm3,122.1 to 154.3 cm3,29.3 to 53.6 cm3,57.2 to 94.3 cm3 and 480.1 to 515.4 cm3,respectively.The theoretical expansion margins of LAD,LCX and RCA in all the three directions were within 2 mm.Conclusion The ranges of movement and volume changes of cardiac substructure are quantitati-vely displayed,and references are provided for the planning of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.[Chinese Medical Equipment Journal,2025,46(3):54-58]
7.Predictive value of stress myocardial perfusion imaging with gated SPECT for cardiac death in patients with chronic kidney disease
Ying ZHANG ; Jian JIAO ; Zhi CHANG ; Xu HAN ; Quan LI ; Junqi LI ; Yehong ZHANG ; Xiaofen XIE ; Wei DONG ; Hongzhi MI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):346-351
Objective:To evaluate the clinical predictive value of SPECT myocardial perfusion imaging (MPI) in the occurrence of cardiac death in patients with chronic kidney disease (CKD).Methods:A retrospective follow-up was performed for 160 patients (109 males, 51 females; age: 68.5(61.0, 74.0) years) who underwent MPI in Beijing Anzhen Hospital, Capital Medical University between June 2017 and March 2024. The 17-segment 5-point method was used for image analysis to obtain the left ventricular myocardial perfusion and functional parameters. The patients were followed up for cardiac death, and divided into death group and survival group. Clinical data of those 2 groups were compare by χ2 test, the independent-sample t test or Mann-Whitney U test. Cox proportional hazards regression analysis was used to analyze the predictors related to cardiac death. The ROC curve was used to analyze the performance of predictors. Survival curves were obtained by the Kaplan-Meier method, and log-rank test was performed to compare the difference between 2 groups. Results:The follow-up time of 160 patients with CKD was 26.0(10.0, 46.5) months. Of 160 patients, 17 died and 143 survived. There were statistically significant differences in body mass index (BMI), previous myocardial infarction, previous revascularization, hypersensitive C-reactive protein (hs-CRP), positive MPI, left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) between the death group and the survival group ( χ2 values: 4.58-16.13, t values: -2.34, -3.97, Z values: from -2.81 to 5.02, all P<0.05). Multivariate Cox regression analysis showed that SSS (hazard ratio ( HR)=1.153, 95% CI: 1.062-1.252, P=0.001) and hs-CRP ( HR=1.031, 95% CI: 1.004-1.058, P=0.023) were independent risk factors for cardiac death in patients with CKD. The optimal cut-off value of SSS for predicting cardiac death in those patients was determined to be 8 with the AUC of 0.815, and the incidence of cardiac death in the SSS ≥8 group was significantly higher than that in the SSS<8 group (33.3%(12/36) vs 4.0%(5/124); χ2 = 25.44, P<0.001). Conclusion:MPI is an important imaging method for the evaluation of cardiac death in patients with CKD, SSS and hs-CRP are important risk factors in predicting cardiac death in those patients.
8.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
9.Establishment and application of ultra-fast real-time PCR for Brucella detection
Zhen-na XU ; Zhi-peng WU ; Wei-bin HONG ; Zhi-shen GUAN ; Qi-ming LIN ; Zuan-lan MO ; Yi-fei YE ; Hai-yan XIE ; Min LI ; Yan-qiu ZHU ; Xiao-jun LI ; Xian-peng ZHANG
Chinese Journal of Zoonoses 2025;41(3):278-283
This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20%to 0.91%,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100%compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.
10.Analysis of toxic material basis of Dryopteris crassirhizoma by UPLC-ESI-MS/MS
Rong-hui ZHENG ; Cui-jie WEI ; Fei-fei XIE ; Xin-ya WAN ; Xiao-jie LIANG ; Zhi-wen DUAN ; Dong-mei SUN ; Xiang-dong CEHN
Chinese Traditional Patent Medicine 2025;47(10):3305-3314
AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95%ethanol cold soaked ultrasonic extract(EC),95%ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2%formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

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