Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common...Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.展开更多
Homoisoflavonoids are in the subclass of the larger family of flavonoids having one more alkyl carbon than flavonoids. Among them, 8-C-Methylated homoisoflavones have not been extensively studied for synthesis and bio...Homoisoflavonoids are in the subclass of the larger family of flavonoids having one more alkyl carbon than flavonoids. Among them, 8-C-Methylated homoisoflavones have not been extensively studied for synthesis and biological evaluation. Author’s current objective is to synthesize 8-C-Methylated homoisoflavones by the reaction of 3-C-methylated dihydrochalcones with N,N’-dimethyl (chloromethylene) ammonium chloride generated in situ from DMF and PCl<sub>5</sub> for one carbon extension at about room temperature. The 3-C-methylated dihydrochalcones were synthesized by the reduction of 3-C-methylated chalcones, which were prepared from 3-C-methylated acetophenones and aromatic aldehydes in the presence of base. All the synthesized novel homoisoflavones’s structures were characterized by NMR and Tandem Mass Spectrometry.展开更多
Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in...Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in the increase in the content of effective components in G.uralensis.Methods:In this study,whole G.uralensis plants were treated with exogenous chitosan,and compre-hensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation,respectively.Effects of chitosan induction on endogenous hormones of G.uralensis were analyzed using an enzyme-linked immunosorbent assay.Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.Results:Chitosan induction significantly increased the levels of flavonoids in G.uralensis;however,the variation in triterpenoids was not substantial.Biological processes,including photosynthesis,secondary metabolism,and abiotic stress responses,were significantly enriched.Additionally,the photosynthetic pathway,photosynthesis-antenna protein pathway,and plant hormone signal transduction pathway were significantly enriched.In the flavonoid biosynthesis pathway,the upstream-related enzyme phenylalanine ammonia-lyase(PAL)and the downstream-related enzymes chalcone synthase(CHS),polyketide reductase(PKR),chalcone isomerase(CHI),and vestitone reductase(VR)were significantly upregulated.Conclusions:Our findings suggest that chitosan induction may promote the tricarboxylic acid(TCA)cycle,and the TCA cycle enhancement significantly upregulated PAL,CHS,PKR,CHI,and VR,the five key enzymes involved in flavonoid synthesis of G.uralensis,indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G.uralensis.Our findings provide a reference for improving the quality of cultivated G.uralensis from the perspective of pharmacodynamic components.展开更多
The suddenness, uncertainty, and randomness of rockbursts directly affect the safety of tunnel construction. The prediction of rockbursts is a fundamental aspect of mitigating or even eliminating rockburst hazards. To...The suddenness, uncertainty, and randomness of rockbursts directly affect the safety of tunnel construction. The prediction of rockbursts is a fundamental aspect of mitigating or even eliminating rockburst hazards. To address the shortcomings of the current rockburst prediction models, which have a limited number of samples and rely on manual test results as the majority of their input features, this paper proposes rockburst prediction models based on multi-featured drilling parameters of rock drilling jumbo. Firstly, four original drilling parameters, namely hammer pressure (Ph), feed pressure (Pf), rotation pressure (Pr), and feed speed (VP), together with the rockburst grades, were collected from 1093 rockburst cases. Then, a feature expansion investigation was performed based on the four original drilling parameters to establish a drilling parameter feature system and a rockburst prediction database containing 42 features. Furthermore, rockburst prediction models based on multi-featured drilling parameters were developed using the extreme tree (ET) algorithm and Bayesian optimization. The models take drilling parameters as input parameters and rockburst grades as output parameters. The effects of Bayesian optimization and the number of drilling parameter features on the model performance were analyzed using the accuracy, precision, recall and F1 value of the prediction set as the model performance evaluation indices. The results show that the Bayesian optimized model with 42 drilling parameter features as inputs performs best, with an accuracy of 91.89%. Finally, the reliability of the models was validated through field tests.展开更多
Using ISSR technique to analyze the diversity and genetic relationship of germplasm resources in 39 Prunus mume Sibe. et Zucc., the result showed that 10 primers were screened with high resolution from 51 primers, 120...Using ISSR technique to analyze the diversity and genetic relationship of germplasm resources in 39 Prunus mume Sibe. et Zucc., the result showed that 10 primers were screened with high resolution from 51 primers, 120 fragments were amplified, of which 98 were polymorphic loci, accounting for 81.67% of total. Tested materials were divided into 3 classes, as was fundamentally accorded with the traditional classification base on horticulture. There was no obvious difference in geographic relationship among the clustering results.展开更多
Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detox...Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detoxifying,reducing swelling and soothing pharynx.In recent years,there has been a notable rise in adverse events,including hepatotoxicity,associated with the use of ST,however,the mechanism behind ST-induced hepatotoxicity is unclear.Methods:The effects of ST on liver injury were investigated in vivo.Then,serum and liver samples were then analyzed using high-throughput metabolomics techniques.Furthermore,the application of network pharmacology and multivariate statistical analysis has been instrumental in identifying and predicting biomarkers and targets linked to liver toxicity.Results:In this study,we found that ST extract has a certain degree of damage to the rat liver.Using UPLC-MS/MS techniques,463 compounds were identified from ST,of which 73 compounds were absorbed in the blood of the STH group.Metabolomics results showed that amino acid metabolic biomarkers were associated with liver toxicity induced by ST.Notably,we identified 22 core ingredient as toxic effects Q-markers of ST through correlation analysis between biomarkers and absorbed components.On this basis,it is concluded by network pharmacology that ST may cause liver toxicity through PI3K-Akt signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,and other pathways.Conclusion:Our findings also demonstrated that the“chemical composition-blood migration component-liver metabolism”stactics has an enormous potential to discern biomarkers and ingredients,and to elaborate the complexity toxicity mechanism of ST.展开更多
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
基金supported by grant from the Project of the National Natural Science Foundation of China(Grant No.82060028)funded by the Yunnan Blood Disease Clinical Medical Center(Grant No.2023YJZX-XY05)+2 种基金the Yunnan Health Commission(L2019003)to TSthe Yunnan Provincial Key Laboratory of Clinical Virology(Grant No.202205AG070005)the Yunnan Provincial Key Laboratory of Innovative Application of Traditional Chinese Medicine.
文摘Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.
文摘Homoisoflavonoids are in the subclass of the larger family of flavonoids having one more alkyl carbon than flavonoids. Among them, 8-C-Methylated homoisoflavones have not been extensively studied for synthesis and biological evaluation. Author’s current objective is to synthesize 8-C-Methylated homoisoflavones by the reaction of 3-C-methylated dihydrochalcones with N,N’-dimethyl (chloromethylene) ammonium chloride generated in situ from DMF and PCl<sub>5</sub> for one carbon extension at about room temperature. The 3-C-methylated dihydrochalcones were synthesized by the reduction of 3-C-methylated chalcones, which were prepared from 3-C-methylated acetophenones and aromatic aldehydes in the presence of base. All the synthesized novel homoisoflavones’s structures were characterized by NMR and Tandem Mass Spectrometry.
基金supported by grants from the National Natural Science Foundation of China(81773838).
文摘Objective:To explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch.(G.uralensis)and to improve the quality of cultivated G.uralensis for both medicine and food and aid in the increase in the content of effective components in G.uralensis.Methods:In this study,whole G.uralensis plants were treated with exogenous chitosan,and compre-hensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation,respectively.Effects of chitosan induction on endogenous hormones of G.uralensis were analyzed using an enzyme-linked immunosorbent assay.Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.Results:Chitosan induction significantly increased the levels of flavonoids in G.uralensis;however,the variation in triterpenoids was not substantial.Biological processes,including photosynthesis,secondary metabolism,and abiotic stress responses,were significantly enriched.Additionally,the photosynthetic pathway,photosynthesis-antenna protein pathway,and plant hormone signal transduction pathway were significantly enriched.In the flavonoid biosynthesis pathway,the upstream-related enzyme phenylalanine ammonia-lyase(PAL)and the downstream-related enzymes chalcone synthase(CHS),polyketide reductase(PKR),chalcone isomerase(CHI),and vestitone reductase(VR)were significantly upregulated.Conclusions:Our findings suggest that chitosan induction may promote the tricarboxylic acid(TCA)cycle,and the TCA cycle enhancement significantly upregulated PAL,CHS,PKR,CHI,and VR,the five key enzymes involved in flavonoid synthesis of G.uralensis,indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G.uralensis.Our findings provide a reference for improving the quality of cultivated G.uralensis from the perspective of pharmacodynamic components.
基金supported by the China Railway Corporation Science and Technology Research and Development Program(Grant Nos.K2020G035 and K2021G024)the National Natural Science Foundation of China(Grant No.52378411).
文摘The suddenness, uncertainty, and randomness of rockbursts directly affect the safety of tunnel construction. The prediction of rockbursts is a fundamental aspect of mitigating or even eliminating rockburst hazards. To address the shortcomings of the current rockburst prediction models, which have a limited number of samples and rely on manual test results as the majority of their input features, this paper proposes rockburst prediction models based on multi-featured drilling parameters of rock drilling jumbo. Firstly, four original drilling parameters, namely hammer pressure (Ph), feed pressure (Pf), rotation pressure (Pr), and feed speed (VP), together with the rockburst grades, were collected from 1093 rockburst cases. Then, a feature expansion investigation was performed based on the four original drilling parameters to establish a drilling parameter feature system and a rockburst prediction database containing 42 features. Furthermore, rockburst prediction models based on multi-featured drilling parameters were developed using the extreme tree (ET) algorithm and Bayesian optimization. The models take drilling parameters as input parameters and rockburst grades as output parameters. The effects of Bayesian optimization and the number of drilling parameter features on the model performance were analyzed using the accuracy, precision, recall and F1 value of the prediction set as the model performance evaluation indices. The results show that the Bayesian optimized model with 42 drilling parameter features as inputs performs best, with an accuracy of 91.89%. Finally, the reliability of the models was validated through field tests.
基金Supported by Science and Technology Planning Project of Guang-dong Province (2007A020300002-6)~~
文摘Using ISSR technique to analyze the diversity and genetic relationship of germplasm resources in 39 Prunus mume Sibe. et Zucc., the result showed that 10 primers were screened with high resolution from 51 primers, 120 fragments were amplified, of which 98 were polymorphic loci, accounting for 81.67% of total. Tested materials were divided into 3 classes, as was fundamentally accorded with the traditional classification base on horticulture. There was no obvious difference in geographic relationship among the clustering results.
基金supported High-level Innovative Talents of Guizhou Province(QianKeHe platform talents-GCC[2023]047)Guizhou Province"14th Five Year Plan"key discipline of traditional Chinese medicine and ethnic medicine(QZYYZDXK(JS)-2021-03)Guizhou Administration of Traditional Chinese Medicine,Traditional Chinese medicine,ethnic medicine science and technology research project(QZYY-2021-098).
文摘Background:Sophorae Tonkinensis Radix et Rhizoma(ST,also known as ShanDouGen)pertains to the Sophora genus,which is generally distributed in Southwest China.As a celebrated folk medicine,it has heat-clearing and detoxifying,reducing swelling and soothing pharynx.In recent years,there has been a notable rise in adverse events,including hepatotoxicity,associated with the use of ST,however,the mechanism behind ST-induced hepatotoxicity is unclear.Methods:The effects of ST on liver injury were investigated in vivo.Then,serum and liver samples were then analyzed using high-throughput metabolomics techniques.Furthermore,the application of network pharmacology and multivariate statistical analysis has been instrumental in identifying and predicting biomarkers and targets linked to liver toxicity.Results:In this study,we found that ST extract has a certain degree of damage to the rat liver.Using UPLC-MS/MS techniques,463 compounds were identified from ST,of which 73 compounds were absorbed in the blood of the STH group.Metabolomics results showed that amino acid metabolic biomarkers were associated with liver toxicity induced by ST.Notably,we identified 22 core ingredient as toxic effects Q-markers of ST through correlation analysis between biomarkers and absorbed components.On this basis,it is concluded by network pharmacology that ST may cause liver toxicity through PI3K-Akt signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,and other pathways.Conclusion:Our findings also demonstrated that the“chemical composition-blood migration component-liver metabolism”stactics has an enormous potential to discern biomarkers and ingredients,and to elaborate the complexity toxicity mechanism of ST.
