Phytomelatonin,an emerging plant hormone,plays vital roles in plant growth,development,and stress adaptation(Arnao et al.,2022;Ullah et al.,2024).It acts both as a direct antioxidant and a signaling molecule,engaging ...Phytomelatonin,an emerging plant hormone,plays vital roles in plant growth,development,and stress adaptation(Arnao et al.,2022;Ullah et al.,2024).It acts both as a direct antioxidant and a signaling molecule,engaging complex networks and interacting with other phytohormones(Liu et al.,2022;Khan et al.,2023).Although phytomelatonin receptors(PMTRs)have been identified in many plants(Wei et al.,2018;Wang et al.,2022;Liu et al.,2025),the downstream signaling mechanisms,particularly receptor-mediated protein modifications and transcriptional regulation,remain poorly characterized.展开更多
High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging ...High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).展开更多
Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation fre...Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation frequently progresses to cirrhosis and,ultimately,malignancy[1].Monitoring the key risk factors involved in the inflammatory-to-cancerous transformation in HCC is crucial for enabling timely intervention and improving patient survival rates.To address this challenge,we analyzed plasma samples collected from healthy volunteers and patients at various stages of HCC progression.展开更多
Exercise,as a non-pharmacological health intervention,has been widely recognized for its beneficial effects,yet its underlying molecular mechanisms remain incompletely understood.The duration,frequency,and intensity o...Exercise,as a non-pharmacological health intervention,has been widely recognized for its beneficial effects,yet its underlying molecular mechanisms remain incompletely understood.The duration,frequency,and intensity of exercise exert distinct physiological impacts on the human body[1].Notably,acute exercise(AE)primarily elicits immediate metabolic responses and immune activation to cope with environmental stimuli,whereas long-term exercise(LE)induces cumulative health benefits across multiple organ systems[2‒4].Aging represents a complex biological process that persists throughout the ontogenetic continuum and serves as a pivotal etiological determinant for numerous chronic pathologies.In the context of accelerating global demographic aging,the development of interventions to promote healthspan extension and modulate aging trajectories has become a paramount research imperative in geroscience.Currently,research on the relationship between exercise and aging is a hot topic.For example,exercise has been shown to modulate aging through pathways such as AMP-activated protein kinase(AMPK)[5].However,the precise molecular links remain elusive.In a recent breakthrough study,Geng et al.used a novel multi-omics strategy to pinpoint betaine,a glycine derivative from choline/diet that serves as both a hepatic methyl donor and a renal osmoprotectant,as a key exercise-induced molecule with anti-inflammatory and geroprotective effects mediated partially via TANK-binding kinase 1(TBK1)inhibition[6,7].This work represents a significant advance as it systematically maps the molecular divergence between acute and long-term exercise while establishing a direct link between renal metabolism and systemic senescence-delaying benefits.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
The"one drug-multiple targets"paradigm has revolutionized therapeutic development for complex diseases by addressing the limitations of single-target approaches[1].However,elucidating multi-target synergism ...The"one drug-multiple targets"paradigm has revolutionized therapeutic development for complex diseases by addressing the limitations of single-target approaches[1].However,elucidating multi-target synergism remains a major challenge.Network pharmacology(NP)enables polypharmacological investigations through biological networks[2].展开更多
Peach(Prunus persica L.Batsch)is the most important temperate fruit crop globally.As a model species for the genus Prunus and other perennial fruit trees in the Rosaceae family,it has gattracted considerable attention...Peach(Prunus persica L.Batsch)is the most important temperate fruit crop globally.As a model species for the genus Prunus and other perennial fruit trees in the Rosaceae family,it has gattracted considerable attention in both biological and agricultural research.So far,12 peach genomes have been sequenced and annotated,providing accurate data support for the genetic basis of peaches.展开更多
The rapid evolution of single-cell technologies has fundamentally transformed our ability to interrogate cellular heterogeneity and biological complexity with unprecedented resolution.Over the past few years,the field...The rapid evolution of single-cell technologies has fundamentally transformed our ability to interrogate cellular heterogeneity and biological complexity with unprecedented resolution.Over the past few years,the field has progressed beyond the creation of purely descriptive“cell atlases”toward a new frontier centered on functional validation and mechanistic dissection of regulatory landscapes.Among them,the launch and implementation of the Hematopoietic Ecosystem Multi-Omics Atlas of billions Blood Cells(HEMO ABC)Project is particularly significant.It aims to comprehensively and precisely characterize a vast number of blood cells,with the goal of constructing a massive database encompassing the characteristics and relationships of various cell types within the blood system.However,such an ambitious project faces numerous challenges.Data generated from different research platforms exhibit heterogeneity,making data integration a formidable task.Moreover,the absence of a unified and standardized technical system to ensure the quality and consistency of research.So this paradigm shift is particularly critical for the highly dynamic and complex hematopoietic ecosystem.展开更多
Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leu...Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.展开更多
Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellula...Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellular and niche events at the precancerous tipping point of early gastric cancer(EGC),we aimed to develop more precise screening tools and design targeted interventions to prevent malignant transformation at this stage.We utilized our AI models to integrate spatial multimodal data from nine EGC endoscopic submucosal dissection(ESD)samples(covering sequential stages from normal to cancer),construct a spatial-temporal profile of disease progression,and identify a critical tipping point(PMC_P)characterized by an immune-suppressive microenvironment during early cancer development.At this stage,inflammatory pit mucous cells with stemness(PMC_2)interact with fibroblasts via NAMPT→ITGA5/ITGB1 and with macrophages via AREG→EGFR/ERBB2 signaling,fostering cancer initiation.We established gastric precancerous cell lines and organoids to demonstrate that NAMPT and AREG promote cellular proliferation in vitro.Furthermore,in the transgenic CEA-SV40 mouse model,targeting AREG and/or NAMPT disrupted key cell interactions,inhibited the JAK-STAT,MAPK,and NFκB pathways,and reduced PD-L1 expression,which was also confirmed by western blot in vitro.These interventions delayed disease progression,reversed the immunosuppressive microenvironment,and prevented malignant transformation.Clinical validation was conducted using endoscopically resected EGC specimens.Our study provides a precise spatiotemporal depiction of EGC development and identifies novel diagnostic markers and therapeutic targets for early intervention.展开更多
Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that i...Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that involve multiple quantitative trait loci and environmental factors(Liu and Yan,2019;Tam et al.,2019).Despite recent advancements in GWAS tools such as GAPIT3(Tang et al.,2016)and HAPPI GWAS(Slaten et al.,2020),which have facilitated the exploration of relationships between molecular and phenotypic traits,these tools still adhere to conventional GWAS designs and exhibit limited capabilities in establishing associations across multi-omics layers.展开更多
Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with...Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with oral paliperidone were analyzed through genotyping,mass spectrometry proteomic,and metabolomic profiling to explore underlying markers and mechanisms of antipsychotic efficacy.Machine learning analysis identified 20 proteins and 20 metabolites at baseline predictive of treatment response.Proteomic and metabolomic models achieved a cross-site mean AUC of 0.923 and 0.816,respectively.A multi-omics ensemble model achieved 0.941.GWAS and differential analyses identified 32 loci(P<5×10-5),83 proteins,and 31 metabolites associated with efficacy(P<0.05).Trans-omics analysis of these efficacy-related molecules across three omic layers highlighted glycerophospholipid metabolism(P=3.25×10-5)and sphingolipid metabolism(P=0.039).Key molecules within these pathways exhibited a consistent direction of effect in regulating phosphatidylcholine(PC)and sphingomyelin(SM)metabolism,and higher PC and SM levels were found to correlate with better efficacy.These associations were further genetically validated using polygenic risk scores in two independent cohorts(2281 and 449 patients,respectively).In conclusion,multi-omics modeling is able to accurately identify antipsychotic efficacy,and higher PC and SM levels correlate with better antipsychotic efficacy,suggesting that variations in phospholipid metabolism may underlie the response to antipsychotics.展开更多
Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adeno...Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.展开更多
Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar...Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar yield is limited by restricted genetic diversity and an exceptionally complex genome.This genetic complexity stems from the polyploid nature of sugarcane,which arose from a historical hybridization between Saccharum officinarum and Saccharum spontaneum.展开更多
To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]Th...To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]The presence of AD significantly impairs patient quality of life and imposes substantial economic burdens on society.In recent years,the potential link between AD and lymphoma has attracted considerable attention from researchers and clinicians.Lymphoma,a malignancy of the lymphatic system,poses significant health risks due to its high mortality potential.[2]However,observational studies investigating the potential correlation between AD and lymphoma have yielded inconsistent results.Consequently,the association between AD and lymphoma remains controversial and warrants further investigation.展开更多
Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,...Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,a huge challenge has also been posed for researchers to deal with the dramatically increasing amount of multi-omics data.展开更多
Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(...Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(HGsc).These alterations often include BRCA1/2 and TP53 mutations,and their impact is further assessed through homologous recombination deficiency(HRD)derived from genomic instability markers such as loss of heterozygosity and telomeric imbalance.展开更多
Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied wi...Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.展开更多
Yogurt is a well-established health food,known for lowering serum cholesterol,promoting gut health,reducing cancer risk,boosting immunity,and easing cognitive impairment[1].It also benefits gastrointestinal disorders ...Yogurt is a well-established health food,known for lowering serum cholesterol,promoting gut health,reducing cancer risk,boosting immunity,and easing cognitive impairment[1].It also benefits gastrointestinal disorders like irritable bowel syndrome,inflammatory bowel disease,and diarrhea[2,3],while probiotic variants enhance immunity,curb allergies,lower cancer risk,and improve mood,potentially reducing depression and anxiety[4-6].展开更多
Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi...Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.展开更多
基金supported by the grants from the Key Research and Development Program of Xinjiang Uygur autonomous region in China(Grant No.2023B02017)the National Key Research and Development Program of China(Grant No.2024YFD2300703)+1 种基金the financial support from the Beijing Rural Revitalization Agricultural Science and Technology Project(Grant No.NY2401080000),BAIC01-2025the 2115 Talent Development Program of China Agricultural University.
文摘Phytomelatonin,an emerging plant hormone,plays vital roles in plant growth,development,and stress adaptation(Arnao et al.,2022;Ullah et al.,2024).It acts both as a direct antioxidant and a signaling molecule,engaging complex networks and interacting with other phytohormones(Liu et al.,2022;Khan et al.,2023).Although phytomelatonin receptors(PMTRs)have been identified in many plants(Wei et al.,2018;Wang et al.,2022;Liu et al.,2025),the downstream signaling mechanisms,particularly receptor-mediated protein modifications and transcriptional regulation,remain poorly characterized.
文摘High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).
基金supported by Liaoning Province Science and Technology Plan Project,China(Grant No.:2022JH2/101300038)Liaoning Provincial Applied Basic Research Project,China(Grant No.:2022020255-JH2/1013)+5 种基金the National Natural Science Foundation of China of China(Grant Nos.:82104379/H3203 and 82104126/H3410)Liaoning Distinguished Professor Project(2017)Liaoning BaiQianWan Talents Program in 2019(A-37)China,Liaoning key Research and Development Program(2018),China,the Natural Science Funds of Liaoning Province,China(Grant No.:2021JH2/10300068)the Basic Scientific Research Project of Higher Education Department of Liaoning Province,China(Grant No.:LJ212410163036)Educational Commission of Liaoning Province of China,China(Grant No.:LJ212410163026).
文摘Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation frequently progresses to cirrhosis and,ultimately,malignancy[1].Monitoring the key risk factors involved in the inflammatory-to-cancerous transformation in HCC is crucial for enabling timely intervention and improving patient survival rates.To address this challenge,we analyzed plasma samples collected from healthy volunteers and patients at various stages of HCC progression.
基金funded by the National Natural Science Foundation of China(grant numbers 32371244 and 92057118 to M.H.)and the 2023 Shanghai Eastern Talent Plan Leading Project(to M.H.)supported by the innovative research team of high-level local universities in Shanghai(grant numbers SHSMUZDCX20212000 and SHSMU-ZDCX20211202 to M.H.)+1 种基金the Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases,and the Fundamental Research Funds for the Central Universities to M.H.labsupported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region(grant number 2025GXNSFAA069105 to M.H.).
文摘Exercise,as a non-pharmacological health intervention,has been widely recognized for its beneficial effects,yet its underlying molecular mechanisms remain incompletely understood.The duration,frequency,and intensity of exercise exert distinct physiological impacts on the human body[1].Notably,acute exercise(AE)primarily elicits immediate metabolic responses and immune activation to cope with environmental stimuli,whereas long-term exercise(LE)induces cumulative health benefits across multiple organ systems[2‒4].Aging represents a complex biological process that persists throughout the ontogenetic continuum and serves as a pivotal etiological determinant for numerous chronic pathologies.In the context of accelerating global demographic aging,the development of interventions to promote healthspan extension and modulate aging trajectories has become a paramount research imperative in geroscience.Currently,research on the relationship between exercise and aging is a hot topic.For example,exercise has been shown to modulate aging through pathways such as AMP-activated protein kinase(AMPK)[5].However,the precise molecular links remain elusive.In a recent breakthrough study,Geng et al.used a novel multi-omics strategy to pinpoint betaine,a glycine derivative from choline/diet that serves as both a hepatic methyl donor and a renal osmoprotectant,as a key exercise-induced molecule with anti-inflammatory and geroprotective effects mediated partially via TANK-binding kinase 1(TBK1)inhibition[6,7].This work represents a significant advance as it systematically maps the molecular divergence between acute and long-term exercise while establishing a direct link between renal metabolism and systemic senescence-delaying benefits.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by the National Key R&D Program of China(2022YFF1203304)the National Natural Science Foundation of China(92474204,32070670,and 32341019)+5 种基金the Ningbo Top Medical and Health Research Program(2023030615 and 2024020919)the Beijing Natural Science Foundation Haidian Origination and Innovation Joint Fund(L222007)the Ningbo Science and Technology Innovation Yongjiang 2035 Project(2023Z226 and 2024Z229)the Major Project of Guangzhou National Laboratory(GZNL2023A03001)the Beijing Nova Program(20240484661)the State Key Laboratory of Systems Medicine for Cancer(KF2422-93).
文摘The"one drug-multiple targets"paradigm has revolutionized therapeutic development for complex diseases by addressing the limitations of single-target approaches[1].However,elucidating multi-target synergism remains a major challenge.Network pharmacology(NP)enables polypharmacological investigations through biological networks[2].
基金supported by the National Natural Science Foundation of China(32472699)the Agricultural Science and Technology Innovation Program(ASTIP)(CAAS-ASTIP-2024-ZFRI)the Central Public-Interest Scientific Institution Basal Research Fund(no.ZGS202209).
文摘Peach(Prunus persica L.Batsch)is the most important temperate fruit crop globally.As a model species for the genus Prunus and other perennial fruit trees in the Rosaceae family,it has gattracted considerable attention in both biological and agricultural research.So far,12 peach genomes have been sequenced and annotated,providing accurate data support for the genetic basis of peaches.
文摘The rapid evolution of single-cell technologies has fundamentally transformed our ability to interrogate cellular heterogeneity and biological complexity with unprecedented resolution.Over the past few years,the field has progressed beyond the creation of purely descriptive“cell atlases”toward a new frontier centered on functional validation and mechanistic dissection of regulatory landscapes.Among them,the launch and implementation of the Hematopoietic Ecosystem Multi-Omics Atlas of billions Blood Cells(HEMO ABC)Project is particularly significant.It aims to comprehensively and precisely characterize a vast number of blood cells,with the goal of constructing a massive database encompassing the characteristics and relationships of various cell types within the blood system.However,such an ambitious project faces numerous challenges.Data generated from different research platforms exhibit heterogeneity,making data integration a formidable task.Moreover,the absence of a unified and standardized technical system to ensure the quality and consistency of research.So this paradigm shift is particularly critical for the highly dynamic and complex hematopoietic ecosystem.
基金supported by the Multi-Center Clinical Research Project of the National Clinical Research Center for Geriatric Diseases(No.NCRCG-PLAGH-20230010)the Key Military Health Project(No.23BJZ25).
文摘Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.
基金supported by Shanghai Oriental Talent Youth Program(QNKJ2024006)National Natural Science Foundation of China(82170555,32300523,32570769,and 62132015)+1 种基金Shanghai Academic/Technology Research Leader(22XD1422400)Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG06).
文摘Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellular and niche events at the precancerous tipping point of early gastric cancer(EGC),we aimed to develop more precise screening tools and design targeted interventions to prevent malignant transformation at this stage.We utilized our AI models to integrate spatial multimodal data from nine EGC endoscopic submucosal dissection(ESD)samples(covering sequential stages from normal to cancer),construct a spatial-temporal profile of disease progression,and identify a critical tipping point(PMC_P)characterized by an immune-suppressive microenvironment during early cancer development.At this stage,inflammatory pit mucous cells with stemness(PMC_2)interact with fibroblasts via NAMPT→ITGA5/ITGB1 and with macrophages via AREG→EGFR/ERBB2 signaling,fostering cancer initiation.We established gastric precancerous cell lines and organoids to demonstrate that NAMPT and AREG promote cellular proliferation in vitro.Furthermore,in the transgenic CEA-SV40 mouse model,targeting AREG and/or NAMPT disrupted key cell interactions,inhibited the JAK-STAT,MAPK,and NFκB pathways,and reduced PD-L1 expression,which was also confirmed by western blot in vitro.These interventions delayed disease progression,reversed the immunosuppressive microenvironment,and prevented malignant transformation.Clinical validation was conducted using endoscopically resected EGC specimens.Our study provides a precise spatiotemporal depiction of EGC development and identifies novel diagnostic markers and therapeutic targets for early intervention.
基金supported by the Biological Breeding-National Science and Technology Major Project(2023ZD0407501 to X.W.)the Pinduoduo-China Agricultural University Research Fund(PC2024A01003 to X.W.)+3 种基金the National Key Research and Development Program of China(2023YFF1000100 to J.Y.)the National Natural Science Foundation of China(32341036 to J.Y.)the Hebei Provincial Science and Technology Plan Project Modern Breeding Industry Science and Technology Innovation Special Project(21326316D and 21326302D to J.Z.)the S&T Program of Hebei(215A7612D to J.Z.).
文摘Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that involve multiple quantitative trait loci and environmental factors(Liu and Yan,2019;Tam et al.,2019).Despite recent advancements in GWAS tools such as GAPIT3(Tang et al.,2016)and HAPPI GWAS(Slaten et al.,2020),which have facilitated the exploration of relationships between molecular and phenotypic traits,these tools still adhere to conventional GWAS designs and exhibit limited capabilities in establishing associations across multi-omics layers.
基金supported by the National Natural Science Foundation of China(82330042,82441005,82501802,82301687,82571710)National Key R&D Program of China(2023YFE0119400)+6 种基金Capital’s Funds for Health Improvement and Research(2024-1-4111)STI2030-Major Projects(2021ZD0200702)Beijing Municipal Health Commission Research Ward Programme(3rd batch)Beijing Nova Program(20230484425)China Postdoctoral Science Foundation(2024M760141)National Postdoctoral Program for Innovative Talents(BX20240029)Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation,the Fundamental Research Funds for the Central Universities(BMU2025YFJHPY044).
文摘Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with oral paliperidone were analyzed through genotyping,mass spectrometry proteomic,and metabolomic profiling to explore underlying markers and mechanisms of antipsychotic efficacy.Machine learning analysis identified 20 proteins and 20 metabolites at baseline predictive of treatment response.Proteomic and metabolomic models achieved a cross-site mean AUC of 0.923 and 0.816,respectively.A multi-omics ensemble model achieved 0.941.GWAS and differential analyses identified 32 loci(P<5×10-5),83 proteins,and 31 metabolites associated with efficacy(P<0.05).Trans-omics analysis of these efficacy-related molecules across three omic layers highlighted glycerophospholipid metabolism(P=3.25×10-5)and sphingolipid metabolism(P=0.039).Key molecules within these pathways exhibited a consistent direction of effect in regulating phosphatidylcholine(PC)and sphingomyelin(SM)metabolism,and higher PC and SM levels were found to correlate with better efficacy.These associations were further genetically validated using polygenic risk scores in two independent cohorts(2281 and 449 patients,respectively).In conclusion,multi-omics modeling is able to accurately identify antipsychotic efficacy,and higher PC and SM levels correlate with better antipsychotic efficacy,suggesting that variations in phospholipid metabolism may underlie the response to antipsychotics.
基金supported by Henan Provincial Key Laboratory of Medicine and Henan Provincial Clinical Medical Research Center for Respiratory Diseases.
文摘Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA0450102 and XDA0460405)the Biological Breeding-National Science and Technology Major Project(2022ZD04017)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y2021038)the Informatization Plan of Chinese Academy of Sciences[CAS-WX2024GC-0602]。
文摘Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar yield is limited by restricted genetic diversity and an exceptionally complex genome.This genetic complexity stems from the polyploid nature of sugarcane,which arose from a historical hybridization between Saccharum officinarum and Saccharum spontaneum.
基金supported by grants from the National Key R&D Program of China(Nos.2022YFC3602002 and 2024YFF0507404)National High Level Hospital Clinical Research Funding(Nos.2022-NHLHCRF-LX-02-03 and 2023-NHLHCRF-YXHZ-ZRZD-06).
文摘To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]The presence of AD significantly impairs patient quality of life and imposes substantial economic burdens on society.In recent years,the potential link between AD and lymphoma has attracted considerable attention from researchers and clinicians.Lymphoma,a malignancy of the lymphatic system,poses significant health risks due to its high mortality potential.[2]However,observational studies investigating the potential correlation between AD and lymphoma have yielded inconsistent results.Consequently,the association between AD and lymphoma remains controversial and warrants further investigation.
基金supported by the National Natural Science Foundation of China(32171917)the Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(2021C02064-3)+1 种基金the Shenzhen Science and Technology Program(KQTD20230301092839007)the China Agricultural Research System(CARS-05).
文摘Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,a huge challenge has also been posed for researchers to deal with the dramatically increasing amount of multi-omics data.
基金supported by the National Natural Science Foundation of China(No.81472441 to X.Chen)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(No.SJCX22_0657 to L.Ruan).
文摘Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(HGsc).These alterations often include BRCA1/2 and TP53 mutations,and their impact is further assessed through homologous recombination deficiency(HRD)derived from genomic instability markers such as loss of heterozygosity and telomeric imbalance.
基金supported by The Brain Tumour Charity(grant number GN-000707)supported by DKTK JF Upgrade Next Gen LOGGIC(B310-JF-LOGGIC-MDE)supported by the DFG through a Heisenberg professorship(BR 3662/5-1)and SFB-1479 Oncoescape-Project ID:441891347(P14)。
文摘Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.
基金supported by the Nei Mongol Autonomous Region Science and Technology Leading Talent Team Project(2022LJRC0003)the National Natural Science Foundation of China(U22A20540)+3 种基金the Fundamental Research Funds of Inner Mongolia Agricultural University(BR221203)the earmarked fund(CARS36)the China Postdoctoral Science Foundation(BX20230162)Novogene Co.,Ltd.for metagenomic sequencing support。
文摘Yogurt is a well-established health food,known for lowering serum cholesterol,promoting gut health,reducing cancer risk,boosting immunity,and easing cognitive impairment[1].It also benefits gastrointestinal disorders like irritable bowel syndrome,inflammatory bowel disease,and diarrhea[2,3],while probiotic variants enhance immunity,curb allergies,lower cancer risk,and improve mood,potentially reducing depression and anxiety[4-6].
基金supported by the Biological Breeding-Major Projects(2023ZD04076)the Pinduoduo-China Agricultural University Research Fund(PC2023B01012)+1 种基金the 2115 Talent Development Program of China Agricultural University,the National Natural Science Foundation of China(32201718)the Science and Technology Demonstration Project of Shandong Province(2024SFGC0402).
文摘Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.
