In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challeng...In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach.In 2022,Escherichia coli,a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence,emerged as the predominant pathogenic bacterium in China.The rapid emergence of antibiotic-resistant E.coli strains has rendered antibiotics insufficient to fight E.coli infections.Traditional Chinese medicine(TCM)has made remarkable contributions to the health of Chinese people for thousands of years,and its significant therapeutic effects have been proven in clinical practice.In this paper,we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E.coli infections.First of all,this review introduces the classification,antibiotic resistance characteristics and mechanisms of E.coli.Then,the TCM formulas and extracts are listed along with their active ingredients against E.coli,including extraction solution,minimum inhibitory concentration(MIC),and the antibacterial mechanisms.In addition,there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E.coli infections,and we provide a summary of this evidence and its underlying mechanisms.In conclusion,we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E.coli infections.We hold the opinion that TCM will play an important role in global health,pharmaceutical development,and livestock farming in the future.展开更多
Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for...Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.展开更多
Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants h...Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants have some differences in efficacy,but the flower buds are easily confused for similar traits.In addition,large-scale cultivation of ornamental rose flowers may lead to a decrease in the effective components of medicinal roses.Therefore,it is necessary to study the chemical composition and make quality evaluation of Rosae Chinensis Flos(Yueji)and Rosae Rugosae Flos(Meigui).Methods:In this study,40 batches of samples including Meigui and Yueji from different regions in China were collected to establish high-performance liquid chromatography fingerprints.Then,the fingerprints data was analyzed using principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis analysis chemometrics to obtain information on intergroup differences,and non-targeted metabolomic techniques were applied to identify and compare chemical compositions of samples which were chosen from groups with large differences.Differential compounds were screened by orthogonal partial least-squares discriminant analysis and S-plot,and finally multi-component quantification was performed to comprehensively evaluate the quality of Yueji and Meigui.Results:The similarity between the fingerprints of 40 batches roses and the reference print R was 0.73 to 0.93,indicating that there were similarities and differences between the samples.Through principal component analysis and hierarchical cluster analysis of fingerprints data,the samples from different origins and varieties were intuitively divided into four groups.Partial least-squares discriminant analysis analysis showed that Meigui and Yueji cluster into two categories and the model was reliable.A total of 89 compounds were identified by high resolution mass spectrometry,mainly were flavonoids and flavonoid glycosides,as well as phenolic acids.Eight differential components were screened out by orthogonal partial least-squares discriminant analysis and S-plot analysis.Quantitative analyses of the eight compounds,including gallic acid,ellagic acid,hyperoside,isoquercitrin,etc.,showed that Yueji was generally richer in phenolic acids and flavonoids than Meigui,and the quality of Yueji from Shandong and Hebei was better.It is worth noting that Xinjiang rose is rich in various components,which is worth focusing on more in-depth research.Conclusion:In this study,the fingerprints of Meigui and Yueji were established.The chemical components information of roses was further improved based on non-targeted metabolomics and mass spectrometry technology.At the same time,eight differential components of Meigui and Yueji were screened out and quantitatively analyzed.The research results provided a scientific basis for the quality control and rational development and utilization of Rosae Chinensis Flos and Rosae Rugosae Flos,and also laid a foundation for the study of their pharmacodynamic material basis.展开更多
BACKGROUND Yiyi Fuzi Baijiang powder(YFB),a classic Chinese medicine,significantly affects ulcerative colitis(UC).However,it remains unclear whether YFB plays a therapeutic role by improving the intestinal flora of UC...BACKGROUND Yiyi Fuzi Baijiang powder(YFB),a classic Chinese medicine,significantly affects ulcerative colitis(UC).However,it remains unclear whether YFB plays a therapeutic role by improving the intestinal flora of UC patients and its active ingredients.AIM To explore the mechanisms of action of YFB in treating UC.METHODS A mouse model of UC was established by drinking 2.5%dextran sulfate sodium(DSS).Mice were treated with YFB.16S rDNA sequencing was used to detect changes in intestinal flora and perform functional predictions.Corresponding target genes of core active ingredients in YFB and UC were obtained using multiple database retrievals and then used to predict the mechanism of over-lapping targets.After screening core ingredients and target genes,AutoDock software was used for molecular docking,and the best binding target was selected to verify binding activity.RESULTS YFB improved DSS-UC mice by restoring body weight,reducing disease activity index,increasing water and food intake,and alleviating diarrhea and local histopathological damage.YFB enhanced beta diversity,decreased pathogenic bacteria such as Turicibacter and Clostridium_sensu_stricto_1,and increased probiotics such as unclassified_f_Lachnospiraceae and Akkermansia.However,it also reduced anaerobic probiotics such as Ruminococcus,Enterorhabdus and Bifidobacterium.Network pharmacology identified 17 pathways,with cancer and adipocytokine signaling pathways showing significant differences in predicting intestinal microbial function.Molecular docking revealed that nuclear factor kappa-B inhibitor A,RELA and NFKB1,and colchamine,morusin and orotinin had docking scores>5.0.CONCLUSION YFB treats UC by reducing harmful bacteria and boosting probiotics to restore intestinal balance,while potentially influencing signaling pathways.展开更多
Medicinal plant diversity(MPD)is an indispensable part of global plant diversity,serving as the foundation for human survival by offering remedies and preventive measures against diseases.However,factors such as overe...Medicinal plant diversity(MPD)is an indispensable part of global plant diversity,serving as the foundation for human survival by offering remedies and preventive measures against diseases.However,factors such as overexploitation,competition from invasive alien species,and climate change,threaten the habitats of medicinal plants,necessitating a comprehensive understanding of their spatial distribution and suitable habitats.We leveraged a decade of field survey data on medicinal plant distribution in the Yinshan Mountains,combined with spatial analysis,species distribution modeling,and the Carnegie Ames Stanford Approach(CASA)to explore the MPD spatial distribution and suitable habitats.Spatial analysis revealed that the central and eastern parts of Yinshan Mountains were the primary MPD hotspots,with no cold spots evident at various spatial scales.As the spatial scale decreased,previous non-significant regions transformed into hotspots,with instances where large-scale hotspots became insignificant.These findings offer valuable guidance for safeguarding and nurturing MPD across diverse spatial scales.In future climate change scenarios within the shared socioeconomic pathways(SSP),the habitat suitability for MPD in the Yinshan Mountains predominantly remains concentrated in the central and eastern regions.Notably,areas with high net primary productivity(NPP)values and abundant vegetation coverage align closely with MPD habitat suitability areas,potentially contributing to the region's rich MPD.展开更多
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and di...A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.展开更多
Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believ...Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.展开更多
The flowering time is a key trait that determines adaptation,yield and quality of crops.Adlay,a traditional cereal crop,has developed a distinctive agricultural industry in Southwest China and Southeast Asian countrie...The flowering time is a key trait that determines adaptation,yield and quality of crops.Adlay,a traditional cereal crop,has developed a distinctive agricultural industry in Southwest China and Southeast Asian countries.However,the currently planted varieties are all semi-domesticated landraces with delayed flowering and excessive height.These defects limit yield improvement per unit area and mechanized harvesting.In this study,a major QTL associated with flowering time and plant height in adlay has been mapped and identified as Cl CCT,a gene having a conserved function and regulatory pathway for inhibiting flowering time and increasing plant height in gramineous crops.Among the six identified haplotypes of Cl CCT,the haplotype with 38-bp insertion in promoter region of Cl CCT has earlier flowering time and wider geographical distribution than other haplotypes.The insertion variation,which arises from the segmental duplication of Cl CCT,can inhibit the expression level of reporter gene and has been used in breeding for early maturity and dwarfing.These research results not only reinforce our understanding of the importance of CCT domain protein in the tropical crops adapting to high-latitude environment,but also provide a validated breeding target for the early maturity and dwarfing of adlay.展开更多
Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BC...Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.展开更多
1.In recent years,climate change has led to drought and severe bark beetle infestations,affecting Norway spruce(Picea abies)across Europe,with detrimental consequences for forest owners,the forestry sector and associa...1.In recent years,climate change has led to drought and severe bark beetle infestations,affecting Norway spruce(Picea abies)across Europe,with detrimental consequences for forest owners,the forestry sector and associated industries.As a result,silviculture now faces the challenge of identifying tree species more resilient to these stressors to mitigate the impacts on forest management,forest-dependent economies and rural livelihoods.The North American Douglas-fir(Pseudotsuga menziesii)has emerged as a promising conifer species,better suited to future climate conditions and capable of producing high timber yields.2.Non-native tree species may affect native biodiversity,yet the impacts of Douglas-fir on native forest biodiversity are not clear.A comprehensive review evaluating the impact of Douglas-fir on faunal and floral biodiversity in European forests is lacking.3.Here,we present the results of a systematic literature review on Douglas-fir effects on native biodiversity,focusing on studies conducted in Europe.For arthropods,sufficient studies were found to do more detailed quantitative assessments.For fungi,birds,plants and soil fauna some studies existed,but only qualitative evaluations could be made.Other taxa were not investigated.4.In the present literature,the effects of Douglas-fir inclusion in stands on native biodiversity,compared to stands of solely native tree species,were mostly non-significant(78.6%,based on 32 studies).Positive effects were noted in 12%of cases,while negative effects were observed in 9.4%(total of 1,936 effects).Above-ground fauna was more extensively studied than below-ground fauna.Mechanisms proposed to explain taxa responses were often discussed but not always formally tested.For arthropods,there were varying effects on diversity between studies evaluating different scales(i.e.,tree-scale vs.stand-scale).In general,differences in effects depended on a range of factors,including stand composition and structure,season,and sampling site and period.5.Our review indicates limited evidence of adverse effects of Douglas-fir on biodiversity in European forests,highlighting a significant knowledge gap due to the scarcity of studies.Douglas-fir's impact on biodiversity likely varies depending on the forest type and management practices.Further research in diverse contexts is crucial to determine optimal levels of admixture and guide forest management.展开更多
The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growt...The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.展开更多
Genetic information has been instrumental in elucidating the relationship between the East Asian Summer Monsoon(EASM)and subtropical evergreen broad-leaved forests(EBLFs).However,how the genomic insights of EBLFs’spe...Genetic information has been instrumental in elucidating the relationship between the East Asian Summer Monsoon(EASM)and subtropical evergreen broad-leaved forests(EBLFs).However,how the genomic insights of EBLFs’species correspond to environmental shifts induced by the EASM remains limited.In this study,we investigated the adaptive mechanisms of evergreen Engelhardia species in response to the EASM through genome sequencing and comparative genomic analyses from the de novo genome assemblies of fiveclosely related Engelhardia taxa and one Rhoiptelea species.Our findingsrevealed that the divergence of evergreen trees from their sister deciduous species is closely associated with the onset and intensification of the EASM.This genomic transitionmayhave coincided with a significantexpansion of the terpene synthase(TPS)gene family in E.fenzelii,driven by four distinct modes of gene duplication.This expansion enhances the biosynthesis of terpene volatiles,providing a defensive mechanism against potential herbivory in EASM affected environments.We also identifieda shared whole-genome duplication(WGD)event across Engelhardia,along with substantial differences in transposable element(TE)composition and activity,which contributed to genome size variation between E.fenzelii and E.roxburghiana.In addition,demographic analyses revealed a continuous population decline over the past 10 million years,further exacerbated by recenthumandisturbance,underscoring the conservation urgency for these species.These results not only provide preliminary insights into the complex evolutionary dynamics within the Engelhardia genus from genomic insights(e.g.,the intricate relationships between genomic variations,environmental changes,and adaptive responses driven by significantclimatic events such as the EASM),but also provides valuable insights into the conservation significance of EBLFs.展开更多
This study presents an approach to enhanced cancer immunotherapy through the in situ synthesis of potassium permanganate(KMnO_(4))derived manganese dioxide(MnO_(2))micro/nano-adjuvants.Addressing the limitations of tr...This study presents an approach to enhanced cancer immunotherapy through the in situ synthesis of potassium permanganate(KMnO_(4))derived manganese dioxide(MnO_(2))micro/nano-adjuvants.Addressing the limitations of traditional immunotherapy due to patient variability and the complexity of the tumor microenvironment,our research establishes KMnO_(4)as a potent immunomodulator that enhances the efficacy of anti-programmed death-ligand 1(αPD-L1)antibodies.The in situ synthesized MnO_(2)adjuvants in the tumor exhibit direct interactions with biological systems,leading to the reduction of MnO_(2)to Mn^(2+)within the tumor,and thereby improving the microenvironment for immune cell activity.Our in vitro and in vivo models demonstrate KMnO_(4)’s capability to induce concentration-dependent cytotoxicity in tumor cells,triggering DNA damage and apoptosis.It also potentiates immunogenic cell death by upregulating calreticulin and high mobility group box 1(HMGB1)on the cell surface.The combination of KMnO_(4)withαPD-L1 antibodies substantially inhibits tumor growth,promotes dendritic cell maturation,and enhances CD8^(+)T cell infiltration,resulting in a significant phenotypic shift in tumor-associated macrophages towards a pro-inflammatory M1 profile.Our findings advocate for further research into the long-term efficacy of KMnO_(4)and its application in diverse tumor models,emphasizing its potential to redefine immune checkpoint blockade therapy and offering a new vista in the fight against cancer.展开更多
Leveraging unique resource advantages of traditional Chinese medicine(TCM)to achieve innovative breakthroughs in research constitutes a core strategic imperative for its inheritance,innovation and development.At prese...Leveraging unique resource advantages of traditional Chinese medicine(TCM)to achieve innovative breakthroughs in research constitutes a core strategic imperative for its inheritance,innovation and development.At present,the academic advances and scientific achievements in TCM serve as a key driving force for industry growth and advancement of the inheritance and innovation of TCM.To continuously strengthen the leading role of academic research,the China Association of Chinese Medicine(CACM)attaches great importance to the latest research directions and academic results in TCM,and spotlights key advances and emerging trends in TCM scholarship.Since 2020,CACM has conducted the selection and release of the“top 10 academic advances in traditional Chinese medicine”on a yearly basis.The selection of“top 10 academic advances in traditional Chinese medicine in 2024”prioritized research that addresses clinical needs,answers scientific questions and drives industrial development.Highlighting exploratory,forward-looking,innovative and groundbreaking achievements,the following 10 breakthroughs were selected through a process of collection,systematic review and expert evaluation:New advances in prevention and treatment of digestive system diseases with“brain-gut”cross-organ strategy,high-level evidence support for prevention and treatment of cardiovascular disease(CVD)continuum with TCM,important breakthrough in the research on prevention and treatment of acute radiation injury with TCM,elucidation of molecular mechanisms underlying“excellent shape and high quality”variation in cultivated American ginseng through domestication,biosynthesis of trace active ingredients such as benzylisoquinoline alkaloids,pilot application of artificial intelligence(AI)technology,research technology for unelucidated constituents of TCM,new drug delivery system in TCM,and establishment and preliminary application of integrated evidence chain-based effectiveness evaluation of TCM(iEC-Eff).展开更多
On-time mapping dynamics of crop area,yield,and production is important for global food security.Such information,however,is often not available.Here,we used satellite information,a spectral-phenology integration appr...On-time mapping dynamics of crop area,yield,and production is important for global food security.Such information,however,is often not available.Here,we used satellite information,a spectral-phenology integration approach for mapping crop area,and a machine learning model for predicting yield in the war-stricken Ukraine.We found that in Ukraine crop area and production declined in 2022 relative to 2017–2021 and 2021 for wintertriticeae crops,which was invaded before the cropping season in February of that year.At the same time,crop area and production for rapeseed increased in Ukraine,with yields consistently lower by 6.5%relative to 2021.The low precipitation and the Russian-Ukrainian conflict-related factors contributed to such yield variations by-1.3%and-0.9%for winter-triticeae crops and-4.2%and-0.5%for rapeseed in 2022.We demonstrate a robust framework for monitoring country-wide crop production dynamics in near real-time,serving as an early-foodsecurity-warning system.展开更多
Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii H...Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.展开更多
Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of cela...Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.展开更多
Fangjiomics is a promising paradigm that enhances research on multi-omics-based pharmacological mechanisms of Fangji from holistic and systematic perspective.We reviewed recent advances in Fangjiomics,focusing on data...Fangjiomics is a promising paradigm that enhances research on multi-omics-based pharmacological mechanisms of Fangji from holistic and systematic perspective.We reviewed recent advances in Fangjiomics,focusing on database and analysis platform development,methodological innovations,and translational applications.Through the integration of Fangji and multi-omics data,multi-level system analysis approaches were developed,encompassing single-target analysis,signaling pathways,multi-targeted network and modules.Fangjiomics has emerged as a key strategy in various areas of Fangji research.To support the high quality development of Fangjiomics,we propose principles and perspectives from the integrated,macro-level,and practical viewpoints.展开更多
Mitochondrial genomes of five Tykhepoda scolopendromorphs(Cryptopidae,Scolopocryptopidae and Plutoniumidae)are sequenced and analyzed using methods of comparative genomics to provide more information on the phylogeny ...Mitochondrial genomes of five Tykhepoda scolopendromorphs(Cryptopidae,Scolopocryptopidae and Plutoniumidae)are sequenced and analyzed using methods of comparative genomics to provide more information on the phylogeny of Scolopendromorpha.The locations of 22 tRNAs,13 PCGs,and 2 rRNAs are annotated.The heavy chain of mitochondrial genomes are 14,841-15,619 bp in length.A+T%vary from 64.79%to 77.40%,and mitochondrial genomes are CG and AT skewed.The phylogenetic reconstructions showed the blind clade,recently named Tykhepoda,is monophyletic with high support values(BS=100%and PP=1).展开更多
基金supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ16-YQ-037,JIPY2023003,and JJPY2022022)China Academy of Chinese Medical Sciences(CACMS)Innovation Fund(Grant No.:CI2021A00601).
文摘In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach.In 2022,Escherichia coli,a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence,emerged as the predominant pathogenic bacterium in China.The rapid emergence of antibiotic-resistant E.coli strains has rendered antibiotics insufficient to fight E.coli infections.Traditional Chinese medicine(TCM)has made remarkable contributions to the health of Chinese people for thousands of years,and its significant therapeutic effects have been proven in clinical practice.In this paper,we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E.coli infections.First of all,this review introduces the classification,antibiotic resistance characteristics and mechanisms of E.coli.Then,the TCM formulas and extracts are listed along with their active ingredients against E.coli,including extraction solution,minimum inhibitory concentration(MIC),and the antibacterial mechanisms.In addition,there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E.coli infections,and we provide a summary of this evidence and its underlying mechanisms.In conclusion,we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E.coli infections.We hold the opinion that TCM will play an important role in global health,pharmaceutical development,and livestock farming in the future.
基金supported by the Science and Technology Innovation Program of Hunan Province(No.2022RC1168)National Natural Science Foundation of China(Nos.82322073,82173846,82304533)+12 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)China Postdoctoral Science Foundation(No.2021M702215)Oriental Scholars of Shanghai Universities(No.TP2022081)Jiangxi Province Thousand Talents Program(No.jxsq2023102168)Young Talent Lifting Project of China Association of Chinese Medicine(No.CACM-(2021-QNRC2-A08))Shanghai Rising-Star Program(No.22QA1409100)Shanghai Sailing Program(No.22YF1445000)2021 Shanghai Science and Technology Innovation Action Plan(No.21S11902800)Three-year Action Plan for Shanghai TCM Development and Inheritance Program(Nos.ZY(2021-2023)-0208,ZY(2021-2023)-0401)High level Key Discipline of National Administration of Traditional Chinese Medicine(No.71)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology。
文摘Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.
基金supported by the key project at the central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(Grant number 2060302)the National Natural Science Foundation of China(Grant number 82373982,82173929).
文摘Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants have some differences in efficacy,but the flower buds are easily confused for similar traits.In addition,large-scale cultivation of ornamental rose flowers may lead to a decrease in the effective components of medicinal roses.Therefore,it is necessary to study the chemical composition and make quality evaluation of Rosae Chinensis Flos(Yueji)and Rosae Rugosae Flos(Meigui).Methods:In this study,40 batches of samples including Meigui and Yueji from different regions in China were collected to establish high-performance liquid chromatography fingerprints.Then,the fingerprints data was analyzed using principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis analysis chemometrics to obtain information on intergroup differences,and non-targeted metabolomic techniques were applied to identify and compare chemical compositions of samples which were chosen from groups with large differences.Differential compounds were screened by orthogonal partial least-squares discriminant analysis and S-plot,and finally multi-component quantification was performed to comprehensively evaluate the quality of Yueji and Meigui.Results:The similarity between the fingerprints of 40 batches roses and the reference print R was 0.73 to 0.93,indicating that there were similarities and differences between the samples.Through principal component analysis and hierarchical cluster analysis of fingerprints data,the samples from different origins and varieties were intuitively divided into four groups.Partial least-squares discriminant analysis analysis showed that Meigui and Yueji cluster into two categories and the model was reliable.A total of 89 compounds were identified by high resolution mass spectrometry,mainly were flavonoids and flavonoid glycosides,as well as phenolic acids.Eight differential components were screened out by orthogonal partial least-squares discriminant analysis and S-plot analysis.Quantitative analyses of the eight compounds,including gallic acid,ellagic acid,hyperoside,isoquercitrin,etc.,showed that Yueji was generally richer in phenolic acids and flavonoids than Meigui,and the quality of Yueji from Shandong and Hebei was better.It is worth noting that Xinjiang rose is rich in various components,which is worth focusing on more in-depth research.Conclusion:In this study,the fingerprints of Meigui and Yueji were established.The chemical components information of roses was further improved based on non-targeted metabolomics and mass spectrometry technology.At the same time,eight differential components of Meigui and Yueji were screened out and quantitatively analyzed.The research results provided a scientific basis for the quality control and rational development and utilization of Rosae Chinensis Flos and Rosae Rugosae Flos,and also laid a foundation for the study of their pharmacodynamic material basis.
基金Supported by Key Project at Central Government Level,No.2060302Key Project of Traditional Chinese Medicine Science and Technology in Shandong Province,No.Z-2023015Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau,No.202328043.
文摘BACKGROUND Yiyi Fuzi Baijiang powder(YFB),a classic Chinese medicine,significantly affects ulcerative colitis(UC).However,it remains unclear whether YFB plays a therapeutic role by improving the intestinal flora of UC patients and its active ingredients.AIM To explore the mechanisms of action of YFB in treating UC.METHODS A mouse model of UC was established by drinking 2.5%dextran sulfate sodium(DSS).Mice were treated with YFB.16S rDNA sequencing was used to detect changes in intestinal flora and perform functional predictions.Corresponding target genes of core active ingredients in YFB and UC were obtained using multiple database retrievals and then used to predict the mechanism of over-lapping targets.After screening core ingredients and target genes,AutoDock software was used for molecular docking,and the best binding target was selected to verify binding activity.RESULTS YFB improved DSS-UC mice by restoring body weight,reducing disease activity index,increasing water and food intake,and alleviating diarrhea and local histopathological damage.YFB enhanced beta diversity,decreased pathogenic bacteria such as Turicibacter and Clostridium_sensu_stricto_1,and increased probiotics such as unclassified_f_Lachnospiraceae and Akkermansia.However,it also reduced anaerobic probiotics such as Ruminococcus,Enterorhabdus and Bifidobacterium.Network pharmacology identified 17 pathways,with cancer and adipocytokine signaling pathways showing significant differences in predicting intestinal microbial function.Molecular docking revealed that nuclear factor kappa-B inhibitor A,RELA and NFKB1,and colchamine,morusin and orotinin had docking scores>5.0.CONCLUSION YFB treats UC by reducing harmful bacteria and boosting probiotics to restore intestinal balance,while potentially influencing signaling pathways.
基金The National Key Research and Development Program of China,No.2021YFE0190100Inner Mongolia Autonomous Region Mongolian Medicine Standardization Project,No.2023-[MB023]The Earmarked Fund for CARS,No.CARS-21。
文摘Medicinal plant diversity(MPD)is an indispensable part of global plant diversity,serving as the foundation for human survival by offering remedies and preventive measures against diseases.However,factors such as overexploitation,competition from invasive alien species,and climate change,threaten the habitats of medicinal plants,necessitating a comprehensive understanding of their spatial distribution and suitable habitats.We leveraged a decade of field survey data on medicinal plant distribution in the Yinshan Mountains,combined with spatial analysis,species distribution modeling,and the Carnegie Ames Stanford Approach(CASA)to explore the MPD spatial distribution and suitable habitats.Spatial analysis revealed that the central and eastern parts of Yinshan Mountains were the primary MPD hotspots,with no cold spots evident at various spatial scales.As the spatial scale decreased,previous non-significant regions transformed into hotspots,with instances where large-scale hotspots became insignificant.These findings offer valuable guidance for safeguarding and nurturing MPD across diverse spatial scales.In future climate change scenarios within the shared socioeconomic pathways(SSP),the habitat suitability for MPD in the Yinshan Mountains predominantly remains concentrated in the central and eastern regions.Notably,areas with high net primary productivity(NPP)values and abundant vegetation coverage align closely with MPD habitat suitability areas,potentially contributing to the region's rich MPD.
基金supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,China(Grant Nos.:CI2023E002 and CI2021A04513)the National Natural Science Foundation of China(Grant Nos.:82204619 and 82274094)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ15-YQ-067 and ZZ16-ND-10-26).
文摘A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
基金supported by the Key Project at the Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)the National Natural Science Foundation of China(No.82104389)+2 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2023E002)the High-level Key Discipline Program of National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023244)China Agricultural Research System of MOF and MARA(No.CARS-21).
文摘Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.
基金supported by the National Natural Science Foundation of China(32241044)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302)+2 种基金China Academy of Chinese Medical Sciences Innovation Fund(CI2023E002)Sichuan Province Natural Science Foundation of China(2022NSFSC1688)Guizhou Province Science and Technology Support Program of China(Qiankehezhongyindi[2024]006-1 and Qiankehezhicheng[2022]Yiban 105)。
文摘The flowering time is a key trait that determines adaptation,yield and quality of crops.Adlay,a traditional cereal crop,has developed a distinctive agricultural industry in Southwest China and Southeast Asian countries.However,the currently planted varieties are all semi-domesticated landraces with delayed flowering and excessive height.These defects limit yield improvement per unit area and mechanized harvesting.In this study,a major QTL associated with flowering time and plant height in adlay has been mapped and identified as Cl CCT,a gene having a conserved function and regulatory pathway for inhibiting flowering time and increasing plant height in gramineous crops.Among the six identified haplotypes of Cl CCT,the haplotype with 38-bp insertion in promoter region of Cl CCT has earlier flowering time and wider geographical distribution than other haplotypes.The insertion variation,which arises from the segmental duplication of Cl CCT,can inhibit the expression level of reporter gene and has been used in breeding for early maturity and dwarfing.These research results not only reinforce our understanding of the importance of CCT domain protein in the tropical crops adapting to high-latitude environment,but also provide a validated breeding target for the early maturity and dwarfing of adlay.
基金supported by the National Key R&D Program of China(2021YFF1200602)the National Science Fund for Excellent Overseas Scholars(0401260011)+3 种基金the National Defense Science and Technology Innovation Fund of Chinese Academy of Sciences(c02022088)the Tianjin Science and Technology Program(20JCZDJC00810)the National Natural Science Foundation of China(82202798)the Shanghai Sailing Program(22YF1404200).
文摘Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.
基金supported by grant klifW018 of the Bavarian State Ministry for Food,Agriculture and Forestry for funding.
文摘1.In recent years,climate change has led to drought and severe bark beetle infestations,affecting Norway spruce(Picea abies)across Europe,with detrimental consequences for forest owners,the forestry sector and associated industries.As a result,silviculture now faces the challenge of identifying tree species more resilient to these stressors to mitigate the impacts on forest management,forest-dependent economies and rural livelihoods.The North American Douglas-fir(Pseudotsuga menziesii)has emerged as a promising conifer species,better suited to future climate conditions and capable of producing high timber yields.2.Non-native tree species may affect native biodiversity,yet the impacts of Douglas-fir on native forest biodiversity are not clear.A comprehensive review evaluating the impact of Douglas-fir on faunal and floral biodiversity in European forests is lacking.3.Here,we present the results of a systematic literature review on Douglas-fir effects on native biodiversity,focusing on studies conducted in Europe.For arthropods,sufficient studies were found to do more detailed quantitative assessments.For fungi,birds,plants and soil fauna some studies existed,but only qualitative evaluations could be made.Other taxa were not investigated.4.In the present literature,the effects of Douglas-fir inclusion in stands on native biodiversity,compared to stands of solely native tree species,were mostly non-significant(78.6%,based on 32 studies).Positive effects were noted in 12%of cases,while negative effects were observed in 9.4%(total of 1,936 effects).Above-ground fauna was more extensively studied than below-ground fauna.Mechanisms proposed to explain taxa responses were often discussed but not always formally tested.For arthropods,there were varying effects on diversity between studies evaluating different scales(i.e.,tree-scale vs.stand-scale).In general,differences in effects depended on a range of factors,including stand composition and structure,season,and sampling site and period.5.Our review indicates limited evidence of adverse effects of Douglas-fir on biodiversity in European forests,highlighting a significant knowledge gap due to the scarcity of studies.Douglas-fir's impact on biodiversity likely varies depending on the forest type and management practices.Further research in diverse contexts is crucial to determine optimal levels of admixture and guide forest management.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32260085,31860064,31660501,31970609,32260718 and 31901870)the Key Projects of the Applied Basic Research Plan of Yunnan Province(Grant No.202301AS070082)+3 种基金the Start-up fund from Xishuangbanna Tropical Botanical Garden,the‘Top Talents Program in Science and Technology’from Yunnan Province,the Major Science and Technology Project in Yunnan Province(Grant Nos.202102AE090042 and 202202AE090036)the Young and Middle-Aged Academic and Technical Leaders Reserve Talent Program in Yunnan Province(Grant No.202205AC160076)China Postdoctoral Science Foundation(Grant No.2019M653849XB)the High-level Talents Introduction Plan of Yunnan Province-Young Talents Special Project。
文摘The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.
基金supported by the National Natural Science Foundation of China(No.42171063)Southeast Asia Biodiversity Research Institute,Chinese Academy of Sciences(No.Y4ZK111B01)+6 种基金the Special Fund for ScientificResearch of Shanghai Landscaping&City Appearance Administrative Bureau(G242414,G242416)the“Yunnan Revitalization Talent Support Program”in Yunnan Province(XDYC-QNRC-2022-0028)Yunnan Revitalization Talent Support Program“Innovation Team”Project(202405AS350019)the CAS“Light of West China”Programthe 14th Five-Year Plan of Xishuangbanna Tropical Botanical Garden,Chinese Academy Sciences(XTBG-1450303)the European Research Council(ERC)under the European Union's Horizon 2020 research and innovation program(No.833522)GhentUniversity(Methusalem funding,BOF.MET.2021.0005.01).
文摘Genetic information has been instrumental in elucidating the relationship between the East Asian Summer Monsoon(EASM)and subtropical evergreen broad-leaved forests(EBLFs).However,how the genomic insights of EBLFs’species correspond to environmental shifts induced by the EASM remains limited.In this study,we investigated the adaptive mechanisms of evergreen Engelhardia species in response to the EASM through genome sequencing and comparative genomic analyses from the de novo genome assemblies of fiveclosely related Engelhardia taxa and one Rhoiptelea species.Our findingsrevealed that the divergence of evergreen trees from their sister deciduous species is closely associated with the onset and intensification of the EASM.This genomic transitionmayhave coincided with a significantexpansion of the terpene synthase(TPS)gene family in E.fenzelii,driven by four distinct modes of gene duplication.This expansion enhances the biosynthesis of terpene volatiles,providing a defensive mechanism against potential herbivory in EASM affected environments.We also identifieda shared whole-genome duplication(WGD)event across Engelhardia,along with substantial differences in transposable element(TE)composition and activity,which contributed to genome size variation between E.fenzelii and E.roxburghiana.In addition,demographic analyses revealed a continuous population decline over the past 10 million years,further exacerbated by recenthumandisturbance,underscoring the conservation urgency for these species.These results not only provide preliminary insights into the complex evolutionary dynamics within the Engelhardia genus from genomic insights(e.g.,the intricate relationships between genomic variations,environmental changes,and adaptive responses driven by significantclimatic events such as the EASM),but also provides valuable insights into the conservation significance of EBLFs.
基金supported by the Natural Science Foundation of Guangdong Province(No.2023A1515030291)the Dongguan Science and Technology of Social Development Program(No.20211800905282)+8 种基金the National Key Research and Development Program of China(Nos.2022YFC2303600,2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTDC-202002)the CACMS Innovation Fund(Nos.CI2023E002,CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Nos.CI2023D003,CI2021B014)the Science and Technology Foundation of Shenzhen(No.JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)the Shenzhen Medical Research Fund(No.B2302051)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(No.CW202002)Shenzhen Science and Technology Program(No.RCBS20210609104424065).
文摘This study presents an approach to enhanced cancer immunotherapy through the in situ synthesis of potassium permanganate(KMnO_(4))derived manganese dioxide(MnO_(2))micro/nano-adjuvants.Addressing the limitations of traditional immunotherapy due to patient variability and the complexity of the tumor microenvironment,our research establishes KMnO_(4)as a potent immunomodulator that enhances the efficacy of anti-programmed death-ligand 1(αPD-L1)antibodies.The in situ synthesized MnO_(2)adjuvants in the tumor exhibit direct interactions with biological systems,leading to the reduction of MnO_(2)to Mn^(2+)within the tumor,and thereby improving the microenvironment for immune cell activity.Our in vitro and in vivo models demonstrate KMnO_(4)’s capability to induce concentration-dependent cytotoxicity in tumor cells,triggering DNA damage and apoptosis.It also potentiates immunogenic cell death by upregulating calreticulin and high mobility group box 1(HMGB1)on the cell surface.The combination of KMnO_(4)withαPD-L1 antibodies substantially inhibits tumor growth,promotes dendritic cell maturation,and enhances CD8^(+)T cell infiltration,resulting in a significant phenotypic shift in tumor-associated macrophages towards a pro-inflammatory M1 profile.Our findings advocate for further research into the long-term efficacy of KMnO_(4)and its application in diverse tumor models,emphasizing its potential to redefine immune checkpoint blockade therapy and offering a new vista in the fight against cancer.
基金supported by the Project of Map of Scientific and Technological Talents in the Field of Traditional Chinese Medicine(No.XMSB20240923106).
文摘Leveraging unique resource advantages of traditional Chinese medicine(TCM)to achieve innovative breakthroughs in research constitutes a core strategic imperative for its inheritance,innovation and development.At present,the academic advances and scientific achievements in TCM serve as a key driving force for industry growth and advancement of the inheritance and innovation of TCM.To continuously strengthen the leading role of academic research,the China Association of Chinese Medicine(CACM)attaches great importance to the latest research directions and academic results in TCM,and spotlights key advances and emerging trends in TCM scholarship.Since 2020,CACM has conducted the selection and release of the“top 10 academic advances in traditional Chinese medicine”on a yearly basis.The selection of“top 10 academic advances in traditional Chinese medicine in 2024”prioritized research that addresses clinical needs,answers scientific questions and drives industrial development.Highlighting exploratory,forward-looking,innovative and groundbreaking achievements,the following 10 breakthroughs were selected through a process of collection,systematic review and expert evaluation:New advances in prevention and treatment of digestive system diseases with“brain-gut”cross-organ strategy,high-level evidence support for prevention and treatment of cardiovascular disease(CVD)continuum with TCM,important breakthrough in the research on prevention and treatment of acute radiation injury with TCM,elucidation of molecular mechanisms underlying“excellent shape and high quality”variation in cultivated American ginseng through domestication,biosynthesis of trace active ingredients such as benzylisoquinoline alkaloids,pilot application of artificial intelligence(AI)technology,research technology for unelucidated constituents of TCM,new drug delivery system in TCM,and establishment and preliminary application of integrated evidence chain-based effectiveness evaluation of TCM(iEC-Eff).
基金supported by the National Natural Science Foundation of China(Grant No.42061144003).
文摘On-time mapping dynamics of crop area,yield,and production is important for global food security.Such information,however,is often not available.Here,we used satellite information,a spectral-phenology integration approach for mapping crop area,and a machine learning model for predicting yield in the war-stricken Ukraine.We found that in Ukraine crop area and production declined in 2022 relative to 2017–2021 and 2021 for wintertriticeae crops,which was invaded before the cropping season in February of that year.At the same time,crop area and production for rapeseed increased in Ukraine,with yields consistently lower by 6.5%relative to 2021.The low precipitation and the Russian-Ukrainian conflict-related factors contributed to such yield variations by-1.3%and-0.9%for winter-triticeae crops and-4.2%and-0.5%for rapeseed in 2022.We demonstrate a robust framework for monitoring country-wide crop production dynamics in near real-time,serving as an early-foodsecurity-warning system.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A03807 and CI2021A01501)the National Natural Science Foundation of China(82330124)+2 种基金the Beijing Municipal Natural Science Foundation(7212186)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)the Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences.
文摘Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.
基金the National Key Research and Development Program of China(2020YFA0908000,2022YFC2303600)the National Natural Science Foundation of China(81903866,82274182)and the Central Public Welfare Research Institutes(ZZ13-YQ-105,ZZ15-YQ-065,ZZ14-YQ-058).
文摘Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
基金National Key Research and Development Project(2023YFC3502903)National Natural Science Foundation of China(82474376)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2023C063YLL).
文摘Fangjiomics is a promising paradigm that enhances research on multi-omics-based pharmacological mechanisms of Fangji from holistic and systematic perspective.We reviewed recent advances in Fangjiomics,focusing on database and analysis platform development,methodological innovations,and translational applications.Through the integration of Fangji and multi-omics data,multi-level system analysis approaches were developed,encompassing single-target analysis,signaling pathways,multi-targeted network and modules.Fangjiomics has emerged as a key strategy in various areas of Fangji research.To support the high quality development of Fangjiomics,we propose principles and perspectives from the integrated,macro-level,and practical viewpoints.
基金This work was supported by National Natural Science Foundation of China(82073972)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZXT2021011)Key Project at Central Government Level:The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(2060302).
文摘Mitochondrial genomes of five Tykhepoda scolopendromorphs(Cryptopidae,Scolopocryptopidae and Plutoniumidae)are sequenced and analyzed using methods of comparative genomics to provide more information on the phylogeny of Scolopendromorpha.The locations of 22 tRNAs,13 PCGs,and 2 rRNAs are annotated.The heavy chain of mitochondrial genomes are 14,841-15,619 bp in length.A+T%vary from 64.79%to 77.40%,and mitochondrial genomes are CG and AT skewed.The phylogenetic reconstructions showed the blind clade,recently named Tykhepoda,is monophyletic with high support values(BS=100%and PP=1).
