To explore the application effect of bio-organic fertilizer Kunyijian in flue-cured tobacco and provide scientific basis for its application in production,a plot trial was conducted with K326,a flue-cured tobacco vari...To explore the application effect of bio-organic fertilizer Kunyijian in flue-cured tobacco and provide scientific basis for its application in production,a plot trial was conducted with K326,a flue-cured tobacco variety,in the Science and Technology Test Base of Xundian County,Yunnan.Taking local fertilizer consumption(control 1)and 70%local fertilizer consumption(control 2)as controls,the following replacement groups were designed:under uniformly replacement 70%local fertilizer consumption,(i)organic fertilizer∶microbial agent=80∶1(kg),+600 kg/ha,+900 kg/ha,+1200 kg/ha,+1500 kg/ha Kunyijian;(ii)organic fertilizer∶microbial agent=40∶1(kg),+900 kg/ha Kunyijian.The results show that in the treatment of 70%local fertilizer consumption+1200 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)],the comprehensive performance of flue-cured tobacco was significantly better than that in the control groups,the yield of tobacco leaves reached 2237.1 kg/ha,the output value was 45505.2 yuan/ha,and the average price of the tobacco leaves was 20.53 yuan/kg.The performance of flue-cured tobacco in the treatment of 70%local fertilizer consumption+1500 kg/ha Kunyijian ranked second.The performance of other fertilization treatments was not good,but it did not differ significantly from that of control 1.In terms of chemical composition of tobacco leaves,partial replacement of chemical fertilizer by bio-organic fertilizer Kunyijian,was beneficial to increase the sugar content and reduce the nicotine and total nitrogen contents in tobacco leaves,especially the treatment of 70%local fertilizer consumption+900 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)],and it was also beneficial to increase the chlorine content in tobacco leaves,especially the treatment of 70%local fertilizer consumption+1500 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)].Therefore,it is feasible to use the bio-organic fertilizer Kunyijian to replace 30%of chemical fertilizer in tobacco production.The rate is recommended to be 900-1500 kg/ha[organic fertilizer∶microbial agent=80∶1(kg)].It is suggested to further strengthen the demonstration and promotion of Kunyijian.展开更多
Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critica...Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critical mediator of BCR signaling,is an attractive target for the treatment of B-cell malignancies.This study aimed to identify a highly potent and selective BTK inhibitor.Methods:Homogeneous time-resolved fluorescence assays were used to screen BTK inhibitors.Typhoon fluorescence imaging and Western blot analysis were used to confirm the effects of SY-1530 on the BCR signaling pathway.Additionally,the anti-tumor activities of SY-1530 were evaluated in TMD8 xenografts and spontaneous canine B-cell lymphoma.Results:We found a novel irreversible and non-competitive inhibitor of BTK,SY-1530,which provided dose-dependent and timedependent inhibition.SY-1530 selectively bound to BTK rather than inducible T-cell kinase;consequently,it did not significantly affect T-cell receptor signaling and caused limited off-target effects.SY-1530 blocked the BCR signaling pathway through downregulation of BTK activity,thus leading to impaired phosphorylation of BTK and its downstream kinases.Moreover,SY-1530 induced apoptosis in a caspase-dependent manner and efficaciously inhibited tumor growth in mouse xenograft models of B-cell malignancy(P<0.001).SY-1530 also induced positive clinical responses in spontaneous canine B-cell lymphoma.Conclusions:SY-1530 is an irreversible and selective BTK inhibitor that shows inhibitory effects on B-cell malignancies by blocking the BCR signaling pathway.Therefore,it may be a promising therapeutic approach for the treatment of B-cell malignancies.展开更多
Glucose is an essential source of energy in human diets.After ingestion,blood glucose levels rapidly increase but soon return to baseline due to the regulatory effects of insulin[1].The glucose absorbed by cells is pr...Glucose is an essential source of energy in human diets.After ingestion,blood glucose levels rapidly increase but soon return to baseline due to the regulatory effects of insulin[1].The glucose absorbed by cells is primarily converted into glycogen in the liver for storage.This glycogen is gradually released as needed to maintain blood glucose levels between meals.展开更多
Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that nc886 is a representative Pol III gene that processes microRNA products via Dicer and fu...Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that nc886 is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that nc886 downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients. However, little is known about the association between nc886 and the EMT signaling pathway. We developed a PC cell model with stable overexpression of nc886 and found that nc886 changed cellular morphology and drove MET. The underlying mechanism may be related to its promotion of SNAIL protein degradation via ubiquitination, but not to its neighboring genes, TGFβ-induced protein (TGFBI) and SMAD5, which are Pol II-transcribed. TGF-β1 also override nc886 promotion of MET via transient suppression the transcription of nc886, promotion of TGFBI or increase in SMAD5 phosphorylation. Both nc886 inhibition and TGFBI activation occur regardless of their methylation status. The literature suggests that MYC inhibition by TGF-β1 is attributed to nc886 downregulation. We incidentally identified MYC-associated zinc finger protein (MAZ) as a suppressive transcription factor of TGFBI, which is controlled by TGF-β1. We elucidate a new mechanism of TGF-β1 differential control of Pol II and the transcription of its neighboring Pol III gene and identify a new EMT unit consisting of nc886 and its neighboring genes.展开更多
Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we r...Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we reveal a previously unidentified function of G6PD.It,even the natural G6PD deficiency-associated mutant without the activity to maintain the normal oxPPP,can antagonize the stresses by supporting the reductive glutamine metabolism and AMPK activation,independently of the NADPH generation by the oxPPP.展开更多
Metabolic reprogramming,such as abnormal utilization of glucose,addiction to glutamine,and increased de-novo lipid synthesis,extensively occurs in proliferating cancer cells,but the underneath rationale has remained t...Metabolic reprogramming,such as abnormal utilization of glucose,addiction to glutamine,and increased de-novo lipid synthesis,extensively occurs in proliferating cancer cells,but the underneath rationale has remained to be elucidated.Based on the concept of the degree of reduction of a compound,we have recently proposed a calculation termed as potential of electron transfer(PET),which is used to characterize the degree of electron redistribution coupled with metabolic transformations.When this calculation is combined with the assumed model of electron balance in a cellular context,the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism.Some interesting properties of PET in cancer cells were also discussed,and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance.Enabling electron transfer could drive metabolic reprogramming in cancer metabolism.Therefore,the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.展开更多
基金Key Project of Yunnan Branch of China National Tobacco Corporation(Research and Integrated Application of Key Techniques for Quality Promotion of Original Honghua Dajinyuan).
文摘To explore the application effect of bio-organic fertilizer Kunyijian in flue-cured tobacco and provide scientific basis for its application in production,a plot trial was conducted with K326,a flue-cured tobacco variety,in the Science and Technology Test Base of Xundian County,Yunnan.Taking local fertilizer consumption(control 1)and 70%local fertilizer consumption(control 2)as controls,the following replacement groups were designed:under uniformly replacement 70%local fertilizer consumption,(i)organic fertilizer∶microbial agent=80∶1(kg),+600 kg/ha,+900 kg/ha,+1200 kg/ha,+1500 kg/ha Kunyijian;(ii)organic fertilizer∶microbial agent=40∶1(kg),+900 kg/ha Kunyijian.The results show that in the treatment of 70%local fertilizer consumption+1200 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)],the comprehensive performance of flue-cured tobacco was significantly better than that in the control groups,the yield of tobacco leaves reached 2237.1 kg/ha,the output value was 45505.2 yuan/ha,and the average price of the tobacco leaves was 20.53 yuan/kg.The performance of flue-cured tobacco in the treatment of 70%local fertilizer consumption+1500 kg/ha Kunyijian ranked second.The performance of other fertilization treatments was not good,but it did not differ significantly from that of control 1.In terms of chemical composition of tobacco leaves,partial replacement of chemical fertilizer by bio-organic fertilizer Kunyijian,was beneficial to increase the sugar content and reduce the nicotine and total nitrogen contents in tobacco leaves,especially the treatment of 70%local fertilizer consumption+900 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)],and it was also beneficial to increase the chlorine content in tobacco leaves,especially the treatment of 70%local fertilizer consumption+1500 kg/ha Kunyijian[organic fertilizer∶microbial agent=80∶1(kg)].Therefore,it is feasible to use the bio-organic fertilizer Kunyijian to replace 30%of chemical fertilizer in tobacco production.The rate is recommended to be 900-1500 kg/ha[organic fertilizer∶microbial agent=80∶1(kg)].It is suggested to further strengthen the demonstration and promotion of Kunyijian.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81622037,81672762,and 81372185)and the Beijing Natural Science Foundation(Grant No.5194023).
文摘Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critical mediator of BCR signaling,is an attractive target for the treatment of B-cell malignancies.This study aimed to identify a highly potent and selective BTK inhibitor.Methods:Homogeneous time-resolved fluorescence assays were used to screen BTK inhibitors.Typhoon fluorescence imaging and Western blot analysis were used to confirm the effects of SY-1530 on the BCR signaling pathway.Additionally,the anti-tumor activities of SY-1530 were evaluated in TMD8 xenografts and spontaneous canine B-cell lymphoma.Results:We found a novel irreversible and non-competitive inhibitor of BTK,SY-1530,which provided dose-dependent and timedependent inhibition.SY-1530 selectively bound to BTK rather than inducible T-cell kinase;consequently,it did not significantly affect T-cell receptor signaling and caused limited off-target effects.SY-1530 blocked the BCR signaling pathway through downregulation of BTK activity,thus leading to impaired phosphorylation of BTK and its downstream kinases.Moreover,SY-1530 induced apoptosis in a caspase-dependent manner and efficaciously inhibited tumor growth in mouse xenograft models of B-cell malignancy(P<0.001).SY-1530 also induced positive clinical responses in spontaneous canine B-cell lymphoma.Conclusions:SY-1530 is an irreversible and selective BTK inhibitor that shows inhibitory effects on B-cell malignancies by blocking the BCR signaling pathway.Therefore,it may be a promising therapeutic approach for the treatment of B-cell malignancies.
文摘Glucose is an essential source of energy in human diets.After ingestion,blood glucose levels rapidly increase but soon return to baseline due to the regulatory effects of insulin[1].The glucose absorbed by cells is primarily converted into glycogen in the liver for storage.This glycogen is gradually released as needed to maintain blood glucose levels between meals.
基金This work was supported by the Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM202010025004)the National Nature Science Foundation of China (No. 81672834 and 81272406).
文摘Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that nc886 is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that nc886 downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients. However, little is known about the association between nc886 and the EMT signaling pathway. We developed a PC cell model with stable overexpression of nc886 and found that nc886 changed cellular morphology and drove MET. The underlying mechanism may be related to its promotion of SNAIL protein degradation via ubiquitination, but not to its neighboring genes, TGFβ-induced protein (TGFBI) and SMAD5, which are Pol II-transcribed. TGF-β1 also override nc886 promotion of MET via transient suppression the transcription of nc886, promotion of TGFBI or increase in SMAD5 phosphorylation. Both nc886 inhibition and TGFBI activation occur regardless of their methylation status. The literature suggests that MYC inhibition by TGF-β1 is attributed to nc886 downregulation. We incidentally identified MYC-associated zinc finger protein (MAZ) as a suppressive transcription factor of TGFBI, which is controlled by TGF-β1. We elucidate a new mechanism of TGF-β1 differential control of Pol II and the transcription of its neighboring Pol III gene and identify a new EMT unit consisting of nc886 and its neighboring genes.
基金supporled in part by grants from the National Nature Science Foundation of China(81972567 and 81672762 to B.L.,81830087,U1602221 and 31771516 to C.C.81802671 and 81872414 to DJ.)Grant CIT&TCD20190333 from the Support Projectof High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,Tianjin Natural Science Foundation(No.18JCONJC79600)+1 种基金Project oflnnovative Research Team of Yunnan Province(2019HCO05)Yunnan Funda-mentall Pesearch Projects(12019FB112 and 202001A070018 to DJ).
文摘Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we reveal a previously unidentified function of G6PD.It,even the natural G6PD deficiency-associated mutant without the activity to maintain the normal oxPPP,can antagonize the stresses by supporting the reductive glutamine metabolism and AMPK activation,independently of the NADPH generation by the oxPPP.
基金This work is supported by Grants from the National Natural Science Foundation of China(No.81972567 to Binghui Li and No.81772843 to Guoguang Ying)Start Grant from Advanced Innovation Center for Human Brain Protection(to Binghui Li).
文摘Metabolic reprogramming,such as abnormal utilization of glucose,addiction to glutamine,and increased de-novo lipid synthesis,extensively occurs in proliferating cancer cells,but the underneath rationale has remained to be elucidated.Based on the concept of the degree of reduction of a compound,we have recently proposed a calculation termed as potential of electron transfer(PET),which is used to characterize the degree of electron redistribution coupled with metabolic transformations.When this calculation is combined with the assumed model of electron balance in a cellular context,the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism.Some interesting properties of PET in cancer cells were also discussed,and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance.Enabling electron transfer could drive metabolic reprogramming in cancer metabolism.Therefore,the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
