OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:...OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.展开更多
Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability.By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Rese...Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability.By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research(ICR)mouse model,we found that a ferroptosis phenomenon may exist.Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days.Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde.Epididymal sperm was also collected for semen analysis,and testicular tissue was collected for ferritin content determination,electron microscope observation of mitochondrial morphology,immunohistochemistry,real-time quantitative polymerase chain reaction,and western blot analysis.Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage,iron accumulation,and mitochondrial damage in the testes of mice.In addition,bisphenol A was confirmed to affect the expression of the ferroptosis-related genes,glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),cyclooxygenase 2(COX2),and acyl-CoA synthetase 4(ACSL4)in mouse testicular tissues.Accordingly,we speculate that bisphenol A induces oxidative stress,which leads to the ferroptosis of testicular cells.Overall,the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.展开更多
OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-...OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)signaling.METHODS:SQD model rats were produced by fasting combined with forced swimming method for15 d.After model assessment,rats were randomly divided into four groups of 10[low/middle/high(L/M/H)Sijunzi decoction dose groups and a normal saline(S)group].Limb holding power(HP)and body mass(BM)were measured after 2 weeks of treatment.Following euthanasia,quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy(TEM).Mitochondrial membrane potential(MMP),adenosine triphosphatase(ATP)and reactive oxygen species(ROS)levels were determined using colorimetric methods,and immunoblot analysis of Microtubule-associated protein light chain 3(LC3)and Sequestosome 1(p62)was performed to monitor mitophagy and AMPK/ULK1 signaling.RESULTS:Compared with control(C)group rats,in the S group,HP was reduced,the myofiber Z line was disordered,mitochondria were scattered,and numerous vacuoles and mitophagy were observed.MMP and ATP levels were reduced,ROS levels were elevated,and LC3B expression,and p-AMPKα(Thr172)/AMPKα,p-ULK1(Ser555)/ULK1,and p-Raptor(Ser792)/Raptor ratios were increased,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were decreased.After treatment,compared with the S group,HP was improved in M and H groups but not in the L group.Mitophagy was reduced in M,H and L groups but the Z line was disordered and vacuolization remained in the L group.ATP levels were elevated in M,H and L groups,and MMPs were elevated in M and H groups but not in the L group.ROS levels were decreased in M,H and L groups,as were LC3B expression and p-Raptor(Ser792)/Raptor ratios,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were increased in M and H groups but not in the L group.p-AMPKα(Thr172)/AMPKαand p-ULK1(Ser555)/ULK1 ratios were decreased in M,H and L groups.CONCLUSIONS:Sijunzi decoction improved HP,possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling.This restored mitochondrial morphology and improved oxidative phosphorylation,which contributed to recovery of limb weakness in SQD model rats.展开更多
Objective To study the inhibitory effects of melatonin and its inhibitory mechanism on the growth of human bladder carcinoma T24. Methods The inhibitory effects of melatonin with various concentrations on the human ...Objective To study the inhibitory effects of melatonin and its inhibitory mechanism on the growth of human bladder carcinoma T24. Methods The inhibitory effects of melatonin with various concentrations on the human bladder carcinoma T24 lines in vitro were determined by MTT assay. The mechanism of the inhibition was observed by flow cytometry (FCM) and transmission electron microscopy (TEM). Results The 30% inhibition concentration (IC 30) value was 0.71 mmol·L -1 and the 50% inhibition concentration (IC 50) value was 1.20 mmol·L -1. The population doubling time of T24 cells treated with melatonin at 0.71 mmol·L -1 was 43.2 hours, which was significant different from that of 34.6 hours of the control group. Using FCM, we found that the cell percentage increased during the G 1 phase, but decreased during the S stage. The degenerated ultra-structure of the cell treated with melatonin was also observed by TEM. Conclusion The results suggest that melatonin can inhibit the growth of human bladder carcinoma T24. The inhibitory effects of melatonin might be the prolonging of the staging from G 1 to S in the cell cycle.展开更多
The wave functions,energy levels and matrix elements of Yb+ions are calculated using the relativistic configuration interaction plus core polarization(RCICP)method.The static and dynamic electric dipole polarizabiliti...The wave functions,energy levels and matrix elements of Yb+ions are calculated using the relativistic configuration interaction plus core polarization(RCICP)method.The static and dynamic electric dipole polarizabilities of the ground state and low-lying excited states are determined.Then,the magic wavelengths of the magnetic sublevel 6s_(1/2,m=1/2)→5d_(3/2,m=±3/2,±1/2)and 6s_(1/2,m=1/2)→5_(d5/2,m=±5/2,±3/2,±1/2)transitions in the linearly,right-handed,and left-handed polarized light are further determined.The dependence of the magic wavelengths upon the angle between the direction of magnetic field and the direction of laser polarization is analyzed.展开更多
Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:...Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.展开更多
Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Pa...Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.展开更多
Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point cult...Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point culture defined this period of socio-political elaboration. However, following a significant period of climate change that led to exceptional flooding and a major reorganization of the course of the Mississippi River, this culture collapsed beginning ca. 3300–3200 cal yr BP and the LMV was abandoned for the subsequent 500 years. In this study, we use data from the Jaketown site in the Yazoo Basin of west-central Mississippi to refine the chronology of the climate event that caused the collapse of the Poverty Point culture. A large flood buried Poverty Point-era occupation deposits at Jaketown around 3310 cal yr BP. Lateral migration of the Mississippi River during flooding led to inundation of the Yazoo Basin and re-occupation of ancient river courses. A coarse sand stratum topped by a more than a meter-thick fining upward sediment package marks a crevasse deposit caused by a rupture of the natural levee at Jaketown. This levee breach was part of a larger pattern of erratic flooding throughout the LMV and is associated with major landscape evolution and the abandonment of Poverty Point sites within the valley. Early Woodland peoples re-colonized the crevasse surface after ca. 2780 cal yr BP. Following this event, the Jaketown site and the eastern Yazoo Basin witnessed a period of landscape stability that lasts to this day. These archaeological data demonstrate how climate change and natural disasters can lead to socio-political dissolution and reorganization even in relatively small-scale hunter-gatherer populations.展开更多
In the field of quantum metrology,transition matrix elements are crucial for accurately evaluating the black-body radiation shift of the clock transition and the amplitude of the related parity-violating transition,an...In the field of quantum metrology,transition matrix elements are crucial for accurately evaluating the black-body radiation shift of the clock transition and the amplitude of the related parity-violating transition,and can be used as probes to test quantum electrodynamic effects,especially at the 10^(−3)–10^(−4)level.We developed a universal experimental approach to precisely determine the dipole transition matrix elements by using the shelving technique,for the species where two transition channels are involved,in which the excitation pulses with increasing duration were utilized to induce shelving,and the resulting shelving probabilities were determined by counting the scattered photons from the excited^(2)P_(1∕2)state to the^(2)S_(1∕2)ground state.Using the scattered photons offers several advantages,including insensitivity to fluctuations in magnetic field,laser intensity,and frequency detuning.An intensity-alternating sequence to minimize detection noise and a real-time approach for background photon correction were implemented in parallel.We applied this technique to a single Yb^(+)ion,and determined the 6p^(2)P_(1∕2)-5d^(2)D_(3∕2)transition matrix element 2.9979(20)ea0,which indicates an order of magnitude improvement over existing reports.By combining our result with the 6p^(2)P_(1∕2)lifetime of 8.12(2)ns,we extracted the 6s^(2)S_(1∕2)-6p^(2)P_(1∕2)transition matrix element to be 2.4703(31)ea0.The accurately determined dipole transition matrix elements can serve as a benchmark for the development of high-precision atomic many-body theoretical methods.展开更多
Objective To observe the compositions of microbial community of thin white tongue coating in chronic atrophic gastritis(CAG)patients.Methods Authors collected thin white tongue coating from CAG patients(30 cases)and h...Objective To observe the compositions of microbial community of thin white tongue coating in chronic atrophic gastritis(CAG)patients.Methods Authors collected thin white tongue coating from CAG patients(30 cases)and healthy controllers(HC,30 cases).The 16S rRNA gene sequencing technology was used to study the bacterial flora of thin white tongue coating.Results(1)The thin white tongue coating had similar compositions of advantageous microbial community in the two groups.Of them,the dominant bacteria of tongue coating at the genus level(the comparative content>0.5%)were Streptococcus(21.85%±4.00%),Neisserian(14.98%±1.21%),Veillonella(6.30%±1.10%),Prevotella(3.92%±0.14%),Leptotrichia(3.89%±1.53%),and Moraxella(0.64%±0.21%).(2)Significant differences existed in the contents of 5 bacteria genera between the two groups.The relative contents of Moraxella,Veillonella,and Leptotrichia in CAG patients were significantly increased(P<0.05)and the relative contents of Stococctus and Alloprevotella in CAG patients were significantly reduced(P<0.01,P<0.05).(3)According to top 35 of the genus heatmap,the dominant bacteria were different between the HC group and the CAG group.The dominant bacteria in the HC group were Streptococcus,Alloprevotella,Prevotella-7,Oribacterium,and unidentified-saccharibacteria.And the dominant bacteria in the CAG group were Solobacterium,Lautropia,Aggregatibacter,Stomatobaculum,Megasphaera,Campylobacter,Lachnoanaerobaculum,Leptotrichia,and Veillonella.Conclusion CAG patients and healthy people have similar basic bacterial structure of the thin white tongue coating.The different structure of microflora may be closely related to the occurrence and development of CAG.展开更多
基金Natural Science Foundation-funded Project:Research on the Effect of Acupuncture in Regulating Bladder Excitability based on the Generation and Transmission of Afferent Information from Urinary Control(No.82174516)Investigation into the Mechanism of Acupuncture-regulated Bladder Excitability based on Sensory Nerve Mechanotransduction Signaling(No.82474645)。
文摘OBJECTIVE:To investigate whether electroacupuncture(EA)therapy for overactive bladder(OAB)exerts its effect by modulating mechanosensitive channels in the urothelium,thereby improving bladder sensory function.METHODS:In this study,a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide.We performed either EA or bladder perfusion with HC-067047[a transient receptor potential vanilloid 4(TRPV4)antagonist]and assessed the efficacy of electroacupuncture in the treatment of OAB in rats via urodynamic determination and Void spot assay.tissue morphology,distribution and expression of the TRPV4protein and the amount of adenosine triphosphate(ATP)and Ca2+released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.RESULTS:EA ameliorated bladder function and voiding behaviour,improved bladder uroepithelial tissue morphology,and significantly reduced the immunofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats.Moreover,the simulated mechanical stimulationinduced increases in Ca^(2+)concentration and the release of ATP and acetylcholine(Ach)from bladder urothelial cells were inhibited.The changes in EA followed the same trend as those in HC-067047.CONCLUSIONS:These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells,which correspondingly decreases the inward flow of extracellular Ca^(2+)and reduces the release of ATP and Ach,thereby attenuating excitatory signals.
基金This work was supported by grant from the National Natural Science Foundation of China(No.8207152171 and No.82205166)。
文摘Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability.By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research(ICR)mouse model,we found that a ferroptosis phenomenon may exist.Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days.Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde.Epididymal sperm was also collected for semen analysis,and testicular tissue was collected for ferritin content determination,electron microscope observation of mitochondrial morphology,immunohistochemistry,real-time quantitative polymerase chain reaction,and western blot analysis.Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage,iron accumulation,and mitochondrial damage in the testes of mice.In addition,bisphenol A was confirmed to affect the expression of the ferroptosis-related genes,glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),cyclooxygenase 2(COX2),and acyl-CoA synthetase 4(ACSL4)in mouse testicular tissues.Accordingly,we speculate that bisphenol A induces oxidative stress,which leads to the ferroptosis of testicular cells.Overall,the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
基金Supported by National Natural Science Foundation of China:the Investigation of Sijunzi Decoction Treating Limb Useless on UPR-Mitophagy-Apoptosis Mechanism in Spleen-Qi Deficiency(No.81803986)Education Department of Liaoning:the Investigation of Yiqi Jianpi Decoction Combined with Metformin Treating Diabetic Muscle Atrophy on UPSMitophagy Through PGC-1α/FOXO3 axis(No.L201940)。
文摘OBJECTIVE:To investigate the efficacy of Sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)signaling.METHODS:SQD model rats were produced by fasting combined with forced swimming method for15 d.After model assessment,rats were randomly divided into four groups of 10[low/middle/high(L/M/H)Sijunzi decoction dose groups and a normal saline(S)group].Limb holding power(HP)and body mass(BM)were measured after 2 weeks of treatment.Following euthanasia,quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy(TEM).Mitochondrial membrane potential(MMP),adenosine triphosphatase(ATP)and reactive oxygen species(ROS)levels were determined using colorimetric methods,and immunoblot analysis of Microtubule-associated protein light chain 3(LC3)and Sequestosome 1(p62)was performed to monitor mitophagy and AMPK/ULK1 signaling.RESULTS:Compared with control(C)group rats,in the S group,HP was reduced,the myofiber Z line was disordered,mitochondria were scattered,and numerous vacuoles and mitophagy were observed.MMP and ATP levels were reduced,ROS levels were elevated,and LC3B expression,and p-AMPKα(Thr172)/AMPKα,p-ULK1(Ser555)/ULK1,and p-Raptor(Ser792)/Raptor ratios were increased,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were decreased.After treatment,compared with the S group,HP was improved in M and H groups but not in the L group.Mitophagy was reduced in M,H and L groups but the Z line was disordered and vacuolization remained in the L group.ATP levels were elevated in M,H and L groups,and MMPs were elevated in M and H groups but not in the L group.ROS levels were decreased in M,H and L groups,as were LC3B expression and p-Raptor(Ser792)/Raptor ratios,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were increased in M and H groups but not in the L group.p-AMPKα(Thr172)/AMPKαand p-ULK1(Ser555)/ULK1 ratios were decreased in M,H and L groups.CONCLUSIONS:Sijunzi decoction improved HP,possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling.This restored mitochondrial morphology and improved oxidative phosphorylation,which contributed to recovery of limb weakness in SQD model rats.
文摘Objective To study the inhibitory effects of melatonin and its inhibitory mechanism on the growth of human bladder carcinoma T24. Methods The inhibitory effects of melatonin with various concentrations on the human bladder carcinoma T24 lines in vitro were determined by MTT assay. The mechanism of the inhibition was observed by flow cytometry (FCM) and transmission electron microscopy (TEM). Results The 30% inhibition concentration (IC 30) value was 0.71 mmol·L -1 and the 50% inhibition concentration (IC 50) value was 1.20 mmol·L -1. The population doubling time of T24 cells treated with melatonin at 0.71 mmol·L -1 was 43.2 hours, which was significant different from that of 34.6 hours of the control group. Using FCM, we found that the cell percentage increased during the G 1 phase, but decreased during the S stage. The degenerated ultra-structure of the cell treated with melatonin was also observed by TEM. Conclusion The results suggest that melatonin can inhibit the growth of human bladder carcinoma T24. The inhibitory effects of melatonin might be the prolonging of the staging from G 1 to S in the cell cycle.
基金the National Key Research and Development Program of China(Grant No.2022YFA1602500)the National Natural Science Foundation of China(Grant Nos.12174316 and 12174268)+2 种基金the Young Teachers Scientific Research Ability Promotion Plan of Northwest Normal University(Grant No.NWNU-LKQN2020-10)the Innovative Fundamental Research Group Project of Gansu Province,China(Grant No.20JR5RA541)the Project of the Educational Commission of Guangdong Province of China(Grant No.2020KTSCX124)。
文摘The wave functions,energy levels and matrix elements of Yb+ions are calculated using the relativistic configuration interaction plus core polarization(RCICP)method.The static and dynamic electric dipole polarizabilities of the ground state and low-lying excited states are determined.Then,the magic wavelengths of the magnetic sublevel 6s_(1/2,m=1/2)→5d_(3/2,m=±3/2,±1/2)and 6s_(1/2,m=1/2)→5_(d5/2,m=±5/2,±3/2,±1/2)transitions in the linearly,right-handed,and left-handed polarized light are further determined.The dependence of the magic wavelengths upon the angle between the direction of magnetic field and the direction of laser polarization is analyzed.
基金Guangxi Science and Technology Base and Talent Project (Guike AD20297013)Guangxi Natural Science Foundat ion Project (2021GXNSFBA220036)The second batch of"Qihuang Project"High-Level Talent Team Cultivation Project of Guangxi University of Traditional Chinese Medicine (2021001)。
文摘Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.
文摘Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.
基金supported by the U.S. National Science Foundation (Grant No. #0827097) with additional support from the Edward S. and Tedi Macias fund at Washington University in St. Louis
文摘Hunter-gatherer communities in the American Southeast reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point culture defined this period of socio-political elaboration. However, following a significant period of climate change that led to exceptional flooding and a major reorganization of the course of the Mississippi River, this culture collapsed beginning ca. 3300–3200 cal yr BP and the LMV was abandoned for the subsequent 500 years. In this study, we use data from the Jaketown site in the Yazoo Basin of west-central Mississippi to refine the chronology of the climate event that caused the collapse of the Poverty Point culture. A large flood buried Poverty Point-era occupation deposits at Jaketown around 3310 cal yr BP. Lateral migration of the Mississippi River during flooding led to inundation of the Yazoo Basin and re-occupation of ancient river courses. A coarse sand stratum topped by a more than a meter-thick fining upward sediment package marks a crevasse deposit caused by a rupture of the natural levee at Jaketown. This levee breach was part of a larger pattern of erratic flooding throughout the LMV and is associated with major landscape evolution and the abandonment of Poverty Point sites within the valley. Early Woodland peoples re-colonized the crevasse surface after ca. 2780 cal yr BP. Following this event, the Jaketown site and the eastern Yazoo Basin witnessed a period of landscape stability that lasts to this day. These archaeological data demonstrate how climate change and natural disasters can lead to socio-political dissolution and reorganization even in relatively small-scale hunter-gatherer populations.
基金National Key Research and Development Program of China(2021YFF0603801)National Natural Science Foundation of China(12204491,12121004,12174402,12174268,11934014)+2 种基金Natural Science Foundation of Hubei Province(2022CFA013)Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y201963,Y2022099)CAS Project for Young Scientists in Basic Research(YSBR-055)。
文摘In the field of quantum metrology,transition matrix elements are crucial for accurately evaluating the black-body radiation shift of the clock transition and the amplitude of the related parity-violating transition,and can be used as probes to test quantum electrodynamic effects,especially at the 10^(−3)–10^(−4)level.We developed a universal experimental approach to precisely determine the dipole transition matrix elements by using the shelving technique,for the species where two transition channels are involved,in which the excitation pulses with increasing duration were utilized to induce shelving,and the resulting shelving probabilities were determined by counting the scattered photons from the excited^(2)P_(1∕2)state to the^(2)S_(1∕2)ground state.Using the scattered photons offers several advantages,including insensitivity to fluctuations in magnetic field,laser intensity,and frequency detuning.An intensity-alternating sequence to minimize detection noise and a real-time approach for background photon correction were implemented in parallel.We applied this technique to a single Yb^(+)ion,and determined the 6p^(2)P_(1∕2)-5d^(2)D_(3∕2)transition matrix element 2.9979(20)ea0,which indicates an order of magnitude improvement over existing reports.By combining our result with the 6p^(2)P_(1∕2)lifetime of 8.12(2)ns,we extracted the 6s^(2)S_(1∕2)-6p^(2)P_(1∕2)transition matrix element to be 2.4703(31)ea0.The accurately determined dipole transition matrix elements can serve as a benchmark for the development of high-precision atomic many-body theoretical methods.
文摘Objective To observe the compositions of microbial community of thin white tongue coating in chronic atrophic gastritis(CAG)patients.Methods Authors collected thin white tongue coating from CAG patients(30 cases)and healthy controllers(HC,30 cases).The 16S rRNA gene sequencing technology was used to study the bacterial flora of thin white tongue coating.Results(1)The thin white tongue coating had similar compositions of advantageous microbial community in the two groups.Of them,the dominant bacteria of tongue coating at the genus level(the comparative content>0.5%)were Streptococcus(21.85%±4.00%),Neisserian(14.98%±1.21%),Veillonella(6.30%±1.10%),Prevotella(3.92%±0.14%),Leptotrichia(3.89%±1.53%),and Moraxella(0.64%±0.21%).(2)Significant differences existed in the contents of 5 bacteria genera between the two groups.The relative contents of Moraxella,Veillonella,and Leptotrichia in CAG patients were significantly increased(P<0.05)and the relative contents of Stococctus and Alloprevotella in CAG patients were significantly reduced(P<0.01,P<0.05).(3)According to top 35 of the genus heatmap,the dominant bacteria were different between the HC group and the CAG group.The dominant bacteria in the HC group were Streptococcus,Alloprevotella,Prevotella-7,Oribacterium,and unidentified-saccharibacteria.And the dominant bacteria in the CAG group were Solobacterium,Lautropia,Aggregatibacter,Stomatobaculum,Megasphaera,Campylobacter,Lachnoanaerobaculum,Leptotrichia,and Veillonella.Conclusion CAG patients and healthy people have similar basic bacterial structure of the thin white tongue coating.The different structure of microflora may be closely related to the occurrence and development of CAG.
