Panax notoginseng,a perennial herb of the genus Panax in the family Araliaceae,has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects.Here,w...Panax notoginseng,a perennial herb of the genus Panax in the family Araliaceae,has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects.Here,we report a high-quality reference genome of P.notoginseng,with a genome size up to 2.66 Gb and a contig N50 of 1.12 Mb,produced with third-generation PacBio sequencing technology.This is the first chromosome-level genome assembly for the genus Panax.Through genome evolution analysis,we explored phylogenetic and whole-genome duplication events and examined their impact on saponin biosynthesis.We performed a detailed transcriptional analysis of P.notoginseng and explored genelevel mechanisms that regulate the formation of characteristic tubercles.Next,we studied the biosynthesis and regulation of saponins at temporal and spatial levels.We combined multi-omics data to identify genes that encode key enzymes in the P.notoginseng terpenoid biosynthetic pathway.Finally,we identified five glycosyltransferase genes whose products catalyzed the formation of different ginsenosides in P.notoginseng.The genetic information obtained in this study provides a resource for further exploration of the growth characteristics,cultivation,breeding,and saponin biosynthesis of P.notoginseng.展开更多
Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries great...Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.展开更多
After germination in the dark,plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem(SAM),which is critical for seedling survival during skotomorphogenesis.The factors ...After germination in the dark,plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem(SAM),which is critical for seedling survival during skotomorphogenesis.The factors that coordinate these processes,particularly SAM repression,remain enigmatic.Plant cuticles,multilayered structures of lipid components on the outermost surface of the aerial epidermis of all land plants,provide protection against desiccation and external environmental stresses.Whether and how cuticles regulate plant development are still unclear.Here,we demonstrate that mutants of BODYGUARD1(BDG1)and long-chain acyl-CoA synthetase2(LACS2),key genes involved in cutin biosynthesis,produce a short hypocotyl with an opened apical hook and cotyledons in which the SAM is activated during skotomorphogenesis.Light signaling represses expression of BDG1 and LACS2,as well as cutin biosynthesis.Transcriptome analysis revealed that cuticles are critical for skotomorphogenesis,particularly for the development and function of chloroplasts.Genetic and molecular analyses showed that decreased HOOKLESS1 expression results in apical hook opening in the mutants.When hypoxia-induced expression of LITTLE ZIPPER2 at the SAM promotes organ initiation in the mutants,the de-repressed expression of cell-cycle genes and the cytokinin response induce the growth of true leaves.Our results reveal previously unrecognized developmental functions of the plant cuticle during skotomorphogenesis and demonstrate a mechanism by which light initiates photomorphogenesis through dynamic regulation of cuticle synthesis to induce coordinated and systemic changes in organ development and growth during the skotomorphogenesis-to-photomorphogenesis transition.展开更多
Objective: To study an anti resistance active exercise training method which is consistent with the principle of “transcendental goal power” to promote the plasticity change of central nervous system (CNS) in order ...Objective: To study an anti resistance active exercise training method which is consistent with the principle of “transcendental goal power” to promote the plasticity change of central nervous system (CNS) in order to recover the motor function after CNS injury, observe its clinical effect and explore its mechanism. Methods: The potential of CNS was induced by six-step Daoyin technique of Chinese medicine, and the potential signal was received in real time by bio-electrical signal receiving equipment and displayed in curve form. Combined with the Operant conditioning biofeedback technique, targeted guidance was given to patients to continuously enhance the action muscle signal intensity and weaken the antagonistic muscle signal intensity, so that the motor program was gradually re-established. Sixty-four patients with hemiplegic elbow dysfunction of old cerebral infarction who had been trained but could not be improved further and had a history of more than 1 year were treated for one course, 90 times and 45 minutes each time. Lovett, Elbow Rom, Fugl-Meyer, program signal intensity and proportion were evaluated before and after treatment. The data were analyzed statistically. Before and after treatment, Lovett MMT, ROM of elbow joint, Fugl Meyer, motor program signal intensity and proportion were assessed, and the data were statistically analyzed. Results: After treatment and before treatment, there was a significant difference between the functional evaluation data (P < 0.01). The function of elbow joint was improved;this is the result of reconstructing the motor program on the basis of developing the potential of CNS by means of the “transcendental goal power” mechanism of the method. There was no recurrence after 6 months of follow-up. Conclusion: The Chinese Medicine Daoyin feedback rehabilitation technique is an effective method to improve elbow joint function of hemiplegia patients with cerebral infarction.展开更多
The real-world vaccine protection rates(VPRs)against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection are critical in formulating future vaccination strategies against the virus.Based on a vary...The real-world vaccine protection rates(VPRs)against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection are critical in formulating future vaccination strategies against the virus.Based on a varying coefficient stochastic epidemic model,we obtain 7 countries’real-world VPRs using daily epidemiological and vaccination data,and find that the VPRs improved with more vaccine doses.The average VPR of the full vaccination was 82%(SE:4%)and 61%(SE:3%)in the pre-Delta and Deltadominated periods,respectively.The Omicron variant reduced the average VPR of the full vaccination to 39%(SE:2%).However,the booster dose restored the VPR to 63%(SE:1%)which was significantly above the 50%threshold in the Omicron-dominated period.Scenario analyses show that the existing vaccination strategies have significantly delayed and reduced the timing and the magnitude of the infection peaks,respectively,and doubling the existing booster coverage would lead to 29%fewer confirmed cases and 17%fewer deaths in the 7 countries compared to the outcomes at the existing booster taking rates.These call for higher full vaccine and booster coverage for all countries.展开更多
Airflow speed is one of the three factors of air-assisted spraying.Optimizing the matching model between airflow speed and target canopy characteristics is an effective way to improve the orchard precision spraying te...Airflow speed is one of the three factors of air-assisted spraying.Optimizing the matching model between airflow speed and target canopy characteristics is an effective way to improve the orchard precision spraying technology,as airflow can significantly affect droplet deposition and drift loss.A simple model of airflow speed was established in this study.First,air-assisted spraying experiments were carried out on a standard simulation canopy to study the airflow speed depended on canopy width,leaf area index,and porosity rate.Second,determined by Ribbon Method and verified by droplet drift data,the airflow speed through the canopy was between 0.5 m/s and 0.7 m/s.Third,multiple tests were carried out under standard simulation canopy with different characteristics,and the airflow speed model was established ultimately:with a fixed leaf area index(LAI),the relationship between canopy upwind boundary airflow speed and canopy width satisfied the exponential model(y=ae^(bx)),and the coefficients a and b are well related to the density of branches and leaves in the canopy.When LAI=3.456,y=2.036e^(1.5887x),R^(2)=0.994;LAI=1.728,y=1.639e^(1.445x),R^(2)=0.972.Orchard growers can acquire needed airflow speed through this simple model,it is quick and precise and appropriate to most growth periods of a variety of fruit trees,such as apples,pears,and vines.展开更多
Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combin...Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.展开更多
To understand the mechanism governing the postharvest senescence of Zizania latifolia(Z.latifolia),and the regulatory mechanism induced by 1-methylcyclopropene(1-MCP)during storage at 25℃,physiobiochemical and conjoi...To understand the mechanism governing the postharvest senescence of Zizania latifolia(Z.latifolia),and the regulatory mechanism induced by 1-methylcyclopropene(1-MCP)during storage at 25℃,physiobiochemical and conjoint analyses of the transcriptome and metabolome were performed.The results indicated that 1-MCP treatment engendered changes in the expression of genes and metabolites during the postharvest storage of Z.latifolia.The 1-MCP treatment maintained a good visual appearance,preserved the cell structure and membrane integrity of Z.latifolia by keeping the expression of membrane-related lipolytic enzymes(and related genes)low and the amount of phosphatidylethanolamine high.Compared to the control group,1-MCP treatment enhanced the activities of antioxidant enzymes,resulting in a decrease of reactive oxygen species and malondialdehyde contents,and thus inhibition of oxidative damage and loss of membrane integrity.In addition,1-MCP treatment retarded the senescence of Z.latifolia by downregulating the expression of ethylene biosynthesis-related genes and promoting upregulation of brassinosteroid insensitive 1 kinase inhibitor 1,calmodulin,glutathione reductase,jasmonate amino acid synthase,and mitogen-activated protein kinase-related genes.Moreover,1-MCP retarded Z.latifolia senescence by inducing the activity of adenosine triphosphate(ATP)biosynthesis-related genes and metabolites.Our findings should facilitate future research on the postharvest storage of Z.latifolia,and could help delay senescence and prolong the storage time for commercial applications.展开更多
基金support from the National Natural Science Foundation of China(nos.81891010,81891013)the Key Project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(no.2060302-1806-03)+1 种基金the High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(no.CIT&TCD20170324)the National Program for Special Support of Eminent Professionals.
文摘Panax notoginseng,a perennial herb of the genus Panax in the family Araliaceae,has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects.Here,we report a high-quality reference genome of P.notoginseng,with a genome size up to 2.66 Gb and a contig N50 of 1.12 Mb,produced with third-generation PacBio sequencing technology.This is the first chromosome-level genome assembly for the genus Panax.Through genome evolution analysis,we explored phylogenetic and whole-genome duplication events and examined their impact on saponin biosynthesis.We performed a detailed transcriptional analysis of P.notoginseng and explored genelevel mechanisms that regulate the formation of characteristic tubercles.Next,we studied the biosynthesis and regulation of saponins at temporal and spatial levels.We combined multi-omics data to identify genes that encode key enzymes in the P.notoginseng terpenoid biosynthetic pathway.Finally,we identified five glycosyltransferase genes whose products catalyzed the formation of different ginsenosides in P.notoginseng.The genetic information obtained in this study provides a resource for further exploration of the growth characteristics,cultivation,breeding,and saponin biosynthesis of P.notoginseng.
基金supported by following funds:National Key Research and Development project of China(2020YFC20052003,to S.Y.)National Science and Technology Major Project for Major New Drugs Innovation and Development under grant(2018ZX09711003,to W.Z.)+3 种基金Key International(Regional)Joint Research Program of National Nature Science Foundation of China(81820108009,to S.Y.)National Nature Science Foundation of China(81800916 to X.S.,31471299 and 81522046 to J.L.)The Nature Science Foundation of Xuzhou(KC20177 to X.S.)Jiangsu Provincial University Fund(19KJA560002 to X.S.).
文摘Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.
基金supported by the National Natural Science Foundation of China(32270340 and 31970824 to X.L.and 32300304 to H.Z.)the project“Fulltime introduction of high-end talent research project”(2020HBQZYC004 and A202105008 to X.L.)from Hebei provincefunding from the Hebei Natural Science Foundation(C2021205013 to X.L.,C2021205043 to L.G.,and C2023205049 to Y.Sun).
文摘After germination in the dark,plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem(SAM),which is critical for seedling survival during skotomorphogenesis.The factors that coordinate these processes,particularly SAM repression,remain enigmatic.Plant cuticles,multilayered structures of lipid components on the outermost surface of the aerial epidermis of all land plants,provide protection against desiccation and external environmental stresses.Whether and how cuticles regulate plant development are still unclear.Here,we demonstrate that mutants of BODYGUARD1(BDG1)and long-chain acyl-CoA synthetase2(LACS2),key genes involved in cutin biosynthesis,produce a short hypocotyl with an opened apical hook and cotyledons in which the SAM is activated during skotomorphogenesis.Light signaling represses expression of BDG1 and LACS2,as well as cutin biosynthesis.Transcriptome analysis revealed that cuticles are critical for skotomorphogenesis,particularly for the development and function of chloroplasts.Genetic and molecular analyses showed that decreased HOOKLESS1 expression results in apical hook opening in the mutants.When hypoxia-induced expression of LITTLE ZIPPER2 at the SAM promotes organ initiation in the mutants,the de-repressed expression of cell-cycle genes and the cytokinin response induce the growth of true leaves.Our results reveal previously unrecognized developmental functions of the plant cuticle during skotomorphogenesis and demonstrate a mechanism by which light initiates photomorphogenesis through dynamic regulation of cuticle synthesis to induce coordinated and systemic changes in organ development and growth during the skotomorphogenesis-to-photomorphogenesis transition.
文摘Objective: To study an anti resistance active exercise training method which is consistent with the principle of “transcendental goal power” to promote the plasticity change of central nervous system (CNS) in order to recover the motor function after CNS injury, observe its clinical effect and explore its mechanism. Methods: The potential of CNS was induced by six-step Daoyin technique of Chinese medicine, and the potential signal was received in real time by bio-electrical signal receiving equipment and displayed in curve form. Combined with the Operant conditioning biofeedback technique, targeted guidance was given to patients to continuously enhance the action muscle signal intensity and weaken the antagonistic muscle signal intensity, so that the motor program was gradually re-established. Sixty-four patients with hemiplegic elbow dysfunction of old cerebral infarction who had been trained but could not be improved further and had a history of more than 1 year were treated for one course, 90 times and 45 minutes each time. Lovett, Elbow Rom, Fugl-Meyer, program signal intensity and proportion were evaluated before and after treatment. The data were analyzed statistically. Before and after treatment, Lovett MMT, ROM of elbow joint, Fugl Meyer, motor program signal intensity and proportion were assessed, and the data were statistically analyzed. Results: After treatment and before treatment, there was a significant difference between the functional evaluation data (P < 0.01). The function of elbow joint was improved;this is the result of reconstructing the motor program on the basis of developing the potential of CNS by means of the “transcendental goal power” mechanism of the method. There was no recurrence after 6 months of follow-up. Conclusion: The Chinese Medicine Daoyin feedback rehabilitation technique is an effective method to improve elbow joint function of hemiplegia patients with cerebral infarction.
基金This research is funded by National Natural Science Foundation of China Grants 92046021,12071013,and 12026607.
文摘The real-world vaccine protection rates(VPRs)against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection are critical in formulating future vaccination strategies against the virus.Based on a varying coefficient stochastic epidemic model,we obtain 7 countries’real-world VPRs using daily epidemiological and vaccination data,and find that the VPRs improved with more vaccine doses.The average VPR of the full vaccination was 82%(SE:4%)and 61%(SE:3%)in the pre-Delta and Deltadominated periods,respectively.The Omicron variant reduced the average VPR of the full vaccination to 39%(SE:2%).However,the booster dose restored the VPR to 63%(SE:1%)which was significantly above the 50%threshold in the Omicron-dominated period.Scenario analyses show that the existing vaccination strategies have significantly delayed and reduced the timing and the magnitude of the infection peaks,respectively,and doubling the existing booster coverage would lead to 29%fewer confirmed cases and 17%fewer deaths in the 7 countries compared to the outcomes at the existing booster taking rates.These call for higher full vaccine and booster coverage for all countries.
基金financially supported by the National Natural Science Foundation of China(Grant No.2016YFD020070).
文摘Airflow speed is one of the three factors of air-assisted spraying.Optimizing the matching model between airflow speed and target canopy characteristics is an effective way to improve the orchard precision spraying technology,as airflow can significantly affect droplet deposition and drift loss.A simple model of airflow speed was established in this study.First,air-assisted spraying experiments were carried out on a standard simulation canopy to study the airflow speed depended on canopy width,leaf area index,and porosity rate.Second,determined by Ribbon Method and verified by droplet drift data,the airflow speed through the canopy was between 0.5 m/s and 0.7 m/s.Third,multiple tests were carried out under standard simulation canopy with different characteristics,and the airflow speed model was established ultimately:with a fixed leaf area index(LAI),the relationship between canopy upwind boundary airflow speed and canopy width satisfied the exponential model(y=ae^(bx)),and the coefficients a and b are well related to the density of branches and leaves in the canopy.When LAI=3.456,y=2.036e^(1.5887x),R^(2)=0.994;LAI=1.728,y=1.639e^(1.445x),R^(2)=0.972.Orchard growers can acquire needed airflow speed through this simple model,it is quick and precise and appropriate to most growth periods of a variety of fruit trees,such as apples,pears,and vines.
基金National Natural Scientific Foundation of China(82071349,82027808,82171952,81771310)West China Hospital of Sichuan University Discipline Excellence Development 1·3·5 Engineering Project(Interdisciplinary Innovation Project,ZYYC08005,ZYJC18041)。
文摘Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.
基金the Qingchuang Science and Technology Support Program of Shandong Provincial College(Lujiaorenzi[2019]No.0.6)the Research Start-up Funding from Nanjing Normal University(184080H202B117)the Doctoral Fund(XY 19BS18)of Heze University(provided to Huibo Song),China.
文摘To understand the mechanism governing the postharvest senescence of Zizania latifolia(Z.latifolia),and the regulatory mechanism induced by 1-methylcyclopropene(1-MCP)during storage at 25℃,physiobiochemical and conjoint analyses of the transcriptome and metabolome were performed.The results indicated that 1-MCP treatment engendered changes in the expression of genes and metabolites during the postharvest storage of Z.latifolia.The 1-MCP treatment maintained a good visual appearance,preserved the cell structure and membrane integrity of Z.latifolia by keeping the expression of membrane-related lipolytic enzymes(and related genes)low and the amount of phosphatidylethanolamine high.Compared to the control group,1-MCP treatment enhanced the activities of antioxidant enzymes,resulting in a decrease of reactive oxygen species and malondialdehyde contents,and thus inhibition of oxidative damage and loss of membrane integrity.In addition,1-MCP treatment retarded the senescence of Z.latifolia by downregulating the expression of ethylene biosynthesis-related genes and promoting upregulation of brassinosteroid insensitive 1 kinase inhibitor 1,calmodulin,glutathione reductase,jasmonate amino acid synthase,and mitogen-activated protein kinase-related genes.Moreover,1-MCP retarded Z.latifolia senescence by inducing the activity of adenosine triphosphate(ATP)biosynthesis-related genes and metabolites.Our findings should facilitate future research on the postharvest storage of Z.latifolia,and could help delay senescence and prolong the storage time for commercial applications.
