Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin ...Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood.Here,we performed a comprehensive analysis of genome resequencing,metabolome,and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN.Metabolites analysis revealed that 72.18%of sesquiterpenes was highly accumulated in HAN compared to JL.Integrated omics analysis found a DBR2-Like(DBR2L)gene may be involved in artemisinin biosynthesis.DBR2L was highly homologous with DBR2,belonged to ORR3 family,and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde.Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A.annua and were clustered into three variation types.The promoter activity of diverse variant types showed obvious differences.Furthermore,the core region(-625 to 0)of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened.Thus,the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis.The promoter variation in DBR2L affects its expression level,and thereby may result in the different yield of artemisinin in varieties of A.annua.It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A.annua,and will assist in a high yield of artemisinin in A.annua.展开更多
Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,str...Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.展开更多
In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts(root, stem, leaf, fl...In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts(root, stem, leaf, flower and fruit) were evaluated. The results indicated that the root possessed the most significant action. Subsequently, U. fissa root(UFR) was subjected to further pharmacological evaluation using the benign prostate hyperplasia(BPH) model rats induced by testosterone propionate. The results revealed that UFR could significantly decrease the prostate index, alter the hyperplasia tissue morphology, suppress the prostatic growth factors of VEGF, EGF, bF GF and KGF, decrease the inflammation factor levels of TNF-α, IL-1β and IL-6, improve the activities of GSH-Px, CAT and SOD and decrease the MDA level in the prostate of the model rats. Moreover, UFR also significantly suppressed the hormone levels of testosterone and dihydrotestosterone. These results indicated that the possible BPH inhibitory mechanisms of UFR were growth factor suppression, hormone level modulation, anti-inflammation, and anti-oxidative stress.展开更多
Cleft lip and/or palate(CLP)are the most common craniofacial malformations in humans.Speech problems often persist even after cleft repair,such that follow-up articulation training is usually required.However,the neur...Cleft lip and/or palate(CLP)are the most common craniofacial malformations in humans.Speech problems often persist even after cleft repair,such that follow-up articulation training is usually required.However,the neural mechanism behind effective articulation training remains largely unknown.We used fMRI to investigate the differences in brain activation,functional connectivity,and effective connectivity across CLP patients with and without articulation training and matched normal participants.We found that training promoted task-related brain activation among the articulation-related brain networks,as well as the global attributes and nodal efficiency in the functional-connectivity-based graph of the network.Our results reveal the neural correlates of effective articulation training in CLP patients,and this could contribute to the future improvement of the post-repair articulation training program.展开更多
Isocitrate dehydrogenase(IDH)is an essential metabolic enzyme in the tricarboxylic acid cycle(TAC).The high mutation frequency of the IDH gene plays a complicated role in gliomas.In addition to affecting gliomas direc...Isocitrate dehydrogenase(IDH)is an essential metabolic enzyme in the tricarboxylic acid cycle(TAC).The high mutation frequency of the IDH gene plays a complicated role in gliomas.In addition to affecting gliomas directly,mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways.IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion.In addition,IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells,also affecting their functioning.In this review,we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas.We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas.Finally,we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.展开更多
Objective:To investigate the analgesic substances in the aerial part of Urtica fissa(Urticae Fissae Herba),commonly used for rheumatoid and rheumatism arthritis.Methods:The analgesic constituents were isolated with th...Objective:To investigate the analgesic substances in the aerial part of Urtica fissa(Urticae Fissae Herba),commonly used for rheumatoid and rheumatism arthritis.Methods:The analgesic constituents were isolated with the active guidance of hot plate and acetic acid writhing models,and identified by comprehensive spectroscopic analysis.Results:Thirteen alkaloids(1–13),two lignans(14,15),and three amides(16–18)were isolated from the active fractions.Among them,compound 1 was a new alkaloid,and compound 6 was a new natural product.The activity evaluation in vivo indicated that various pyrrole alkaloids(1,3,6,and 12)possessed significant analgesic activities,they could significantly inhibit the mice pain response induced by acetic acid and hot plate at the dosage of 2 mg/kg BW.Conclusion:The study revealed that the pyrrole alkaloids played important roles in the analgesic activities of Urticae Fissae Herba.展开更多
Naturally occurring secolignans have drawn the considerable attention because of their novel structures and diverse biological activities.In recent years,various natural secolignans with extensive bioactivities have b...Naturally occurring secolignans have drawn the considerable attention because of their novel structures and diverse biological activities.In recent years,various natural secolignans with extensive bioactivities have been reported in the literatures.In the present review,we summarized all the available information regarding the biosynthesis,distributions,separation methods,chemical structures,spectral characteristics,and biological activities of natural secolignans,and provided some valuable new insights for the further study.展开更多
基金supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ13-YQ-101,ZZ16-ND-10-09,ZZ16-ND-10-28)the CACMS Innovation Fund(CI2021A04107),the National Natural Science Foundation of China(U1812403-1)+1 种基金the National Key Research and Development Project(2019YFE0108700,China)the Fundamental Research Funds for the Central Universities(3332022051).
文摘Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood.Here,we performed a comprehensive analysis of genome resequencing,metabolome,and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN.Metabolites analysis revealed that 72.18%of sesquiterpenes was highly accumulated in HAN compared to JL.Integrated omics analysis found a DBR2-Like(DBR2L)gene may be involved in artemisinin biosynthesis.DBR2L was highly homologous with DBR2,belonged to ORR3 family,and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde.Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A.annua and were clustered into three variation types.The promoter activity of diverse variant types showed obvious differences.Furthermore,the core region(-625 to 0)of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened.Thus,the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis.The promoter variation in DBR2L affects its expression level,and thereby may result in the different yield of artemisinin in varieties of A.annua.It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A.annua,and will assist in a high yield of artemisinin in A.annua.
基金supported by the National Natural Science Foundation of China(No.82371515)the Talent Initiation BaiRen Plan Start-up Funds(No.E251F811)the State Key Laboratory of Integrated Management of Pest Insects and Rodents(No.IPM2301),China.
文摘Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.
基金National Natural Science Fund of China(Grant No.81374067)Shanghai Municipal Health Commission(Grant No.2018ZY002)College Students’Innovation Project(Grant No.IPP20216).
文摘In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts(root, stem, leaf, flower and fruit) were evaluated. The results indicated that the root possessed the most significant action. Subsequently, U. fissa root(UFR) was subjected to further pharmacological evaluation using the benign prostate hyperplasia(BPH) model rats induced by testosterone propionate. The results revealed that UFR could significantly decrease the prostate index, alter the hyperplasia tissue morphology, suppress the prostatic growth factors of VEGF, EGF, bF GF and KGF, decrease the inflammation factor levels of TNF-α, IL-1β and IL-6, improve the activities of GSH-Px, CAT and SOD and decrease the MDA level in the prostate of the model rats. Moreover, UFR also significantly suppressed the hormone levels of testosterone and dihydrotestosterone. These results indicated that the possible BPH inhibitory mechanisms of UFR were growth factor suppression, hormone level modulation, anti-inflammation, and anti-oxidative stress.
基金We are grateful to all the patients and healthy controls for their generous participation in this study.This work was supported by grants from the National Natural Science Foundation of China(81771909,61701323,and 62171300)the Discipline Construction Foundation of Beijing Stomatological Hospital(19-09-24)+1 种基金the Capital Medical University Research and Development Fund(PYZ19081)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(XML201714).
文摘Cleft lip and/or palate(CLP)are the most common craniofacial malformations in humans.Speech problems often persist even after cleft repair,such that follow-up articulation training is usually required.However,the neural mechanism behind effective articulation training remains largely unknown.We used fMRI to investigate the differences in brain activation,functional connectivity,and effective connectivity across CLP patients with and without articulation training and matched normal participants.We found that training promoted task-related brain activation among the articulation-related brain networks,as well as the global attributes and nodal efficiency in the functional-connectivity-based graph of the network.Our results reveal the neural correlates of effective articulation training in CLP patients,and this could contribute to the future improvement of the post-repair articulation training program.
基金supported by the Translational Medicine Research Fund of Zhongnan Hospital of Wuhan University(ZLYNXM202011 and ZNLH201901)the National Health Commission of China(2018ZX-07S-011).
文摘Isocitrate dehydrogenase(IDH)is an essential metabolic enzyme in the tricarboxylic acid cycle(TAC).The high mutation frequency of the IDH gene plays a complicated role in gliomas.In addition to affecting gliomas directly,mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways.IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion.In addition,IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells,also affecting their functioning.In this review,we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas.We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas.Finally,we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
基金financially supported by a grant of National Natural Science Foundation of China (No.81374067)Shanghai Municipal Natural Science Foundation (No.20ZR1427700)Shanghai Municipal Health Commission (No.2018ZY002)
文摘Objective:To investigate the analgesic substances in the aerial part of Urtica fissa(Urticae Fissae Herba),commonly used for rheumatoid and rheumatism arthritis.Methods:The analgesic constituents were isolated with the active guidance of hot plate and acetic acid writhing models,and identified by comprehensive spectroscopic analysis.Results:Thirteen alkaloids(1–13),two lignans(14,15),and three amides(16–18)were isolated from the active fractions.Among them,compound 1 was a new alkaloid,and compound 6 was a new natural product.The activity evaluation in vivo indicated that various pyrrole alkaloids(1,3,6,and 12)possessed significant analgesic activities,they could significantly inhibit the mice pain response induced by acetic acid and hot plate at the dosage of 2 mg/kg BW.Conclusion:The study revealed that the pyrrole alkaloids played important roles in the analgesic activities of Urticae Fissae Herba.
基金National Natural Science Foundation of China(Grant No.81374067)Shanghai Municipal Health Commission(Grant No.2018ZY002)
文摘Naturally occurring secolignans have drawn the considerable attention because of their novel structures and diverse biological activities.In recent years,various natural secolignans with extensive bioactivities have been reported in the literatures.In the present review,we summarized all the available information regarding the biosynthesis,distributions,separation methods,chemical structures,spectral characteristics,and biological activities of natural secolignans,and provided some valuable new insights for the further study.