The chaotic systems of average monthly air temperature of Qingdao (SATQ) and the day SST of equatorial local area (DSSELA) are firstly studied by means of the sequency spectral method. It is shown that SATQ contains o...The chaotic systems of average monthly air temperature of Qingdao (SATQ) and the day SST of equatorial local area (DSSELA) are firstly studied by means of the sequency spectral method. It is shown that SATQ contains one-a period of predominant oscillation, two-a periods lower frepqency oscillation and 90-d, 63-d, 50-d, 40-d and 29-d lower frequency periods oscillation in DSSELA. Further more, the discrepancies between sequency spectrum and frequency spectrum are compared in this paper.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Bit_reversed sequency order or bit_reversed Walsh order (M) is presented. Walsh functions in this order can be processed easily, and there is a simple relation between sequency order and bit_reversed sequency order. 8...Bit_reversed sequency order or bit_reversed Walsh order (M) is presented. Walsh functions in this order can be processed easily, and there is a simple relation between sequency order and bit_reversed sequency order. 8 fast algorithms for discrete Walsh transform in bit_reversed sequency order are given.展开更多
Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown ...Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.展开更多
Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as ...Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.展开更多
Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches...Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.展开更多
Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types ...Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.展开更多
Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in m...Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.展开更多
Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe n...Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mu...Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.展开更多
An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascert...An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascertain at early infection stages owing to the unfavourable transcript representation compared to the host genes.In this study,we compare two sequencing techniques,RNAseq and enrichment sequencing(RenSeq and PenSeq)of cDNA,to investigate gene expression patterns in the doubled monoploid potato(DM)infected with the late blight pathogen Phytophthora infestans.Our results reveal distinct advantages of cDNA RenSeq and PenSeq over traditional RNAseq in terms of target gene representation and transcriptional quantification at early infection stages.Throughout the infection time course,cDNA enrichment sequencing enables transcriptomic analyses for more targeted host and pathogen genes.For highly expressed genes that were sampled in parallel by both cDNA enrichment and RNAseq,a high level of concordance in expression profiles is observed,indicative of at least semi-quantitative gene expression representation following enrichment.展开更多
Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used si...Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.展开更多
The Fushan Depression is one of the petroliferous depressions in the Beibuwan Basin,South China Sea.Previous studies have preliminarily explored the origin and source of crude oils in some areas of this depression.Nev...The Fushan Depression is one of the petroliferous depressions in the Beibuwan Basin,South China Sea.Previous studies have preliminarily explored the origin and source of crude oils in some areas of this depression.Nevertheless,no systematic investigations on the classification and origin of oils and hy-drocarbon migration processes have been made for the entire petroleum system in this depression,which has significantly hindered the hydrocarbon exploration in the region.A total of 32 mudstone and 58 oil samples from the Fushan Depression were analyzed to definite the detailed oil-source correlation within the sequence and sedimentary framework.The organic matter of third member of Paleogene Liushagang Formation(Els(3))source rocks,both deltaic and lacustrine mudstone,are algal-dominated with high abundance of C_(23)tricyclic terpane and C_(30)4-methylsteranes.The deltaic source rocks occur-ring in the first member(Els_(1))and second member(Els_(2))of the Paleogene Liushagang Formation are characterized by high abundance of C_(19+20)tricyclic terpane and oleanane,reflecting a more terrestrial plants contribution.While lacustrine source rocks of Els_(1)and Els_(2)display the reduced input of terrige-nous organic matter with relatively low abundance of C 19+20 tricyclic terpane and oleanane.Three types of oils were identified by their biomarker compositions in this study.Most of the oils discovered in the Huachang and Bailian Els_(1)reservoir belong to group A and were derived from lacustrine source rocks of Els_(1)and Els_(2).Group B oils are found within the Els_(1)and Els_(2)reservoirs,showing a close relation to the deltaic source rocks of Els_(1)and Els_(2),respectively.Group C oils,occurring in the Els3 reservoirs,have a good affinity with the Els3 source rocks.The spatial distribution and accumulation of different groups of oils are mainly controlled by the sedimentary facies and specific structural conditions.The Els_(2)reservoir in the Yong'an area belonging to Group B oil,are adjacent to the source kitchen and could be considered as the favorable exploration area in the future.展开更多
Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities...Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.展开更多
BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,ot...BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.展开更多
基金National Natural Science Foundation of China under contract No. 49776285.
文摘The chaotic systems of average monthly air temperature of Qingdao (SATQ) and the day SST of equatorial local area (DSSELA) are firstly studied by means of the sequency spectral method. It is shown that SATQ contains one-a period of predominant oscillation, two-a periods lower frepqency oscillation and 90-d, 63-d, 50-d, 40-d and 29-d lower frequency periods oscillation in DSSELA. Further more, the discrepancies between sequency spectrum and frequency spectrum are compared in this paper.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
文摘Bit_reversed sequency order or bit_reversed Walsh order (M) is presented. Walsh functions in this order can be processed easily, and there is a simple relation between sequency order and bit_reversed sequency order. 8 fast algorithms for discrete Walsh transform in bit_reversed sequency order are given.
基金supported by the National Natural Science Foundation of China,Nos.82471123,82171053the Jilin Province Special Project for Talent in Medical and Health Sciences,No.2024WSXK-E01the Natural Science Foundation of Jilin Province,YDZJ202501ZYTS318(all to GL).
文摘Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
文摘Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.
文摘Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.
基金supported by the Jiangsu Province Traditional Chinese Medicine Technology Development Plan Project,Nos.MS2023113(to JC),MS2022090Young and Middle-aged Academic Leaders of Jiangsu Qing-Lan Project(to GL).
文摘Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.
基金supported by the National Science Foundation of China(No.82405004,82474253)the Natural Science Foundation postdoctoral project of Chongqing(CSTB2022NSCQ-BHX0709)+2 种基金Chongqing Wanzhou District doctoral“through train”scientific research project(wzstc-20220124)Natural Science Foundation of Chongqing,China(No.Cstc2021jcyj-msxmX0996)Chongqing Wanzhou District Science and Health Joint Medical Research Project(wzstc-kw2023032)。
文摘Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.
基金supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX)the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL)+1 种基金Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY)the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。
文摘Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
文摘Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.
基金supported by the Rural & Environment Science & Analytical Services (RESAS) Division of the Scottish Government through project JHI-B1-1the Biotechnology and Biological Sciences Research Council (BBSRC) through awards BB/ S015663/1+2 种基金BB/X009068/1Research Leaders 2025 fellowship funded by European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 754380the Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the “UK’s Crop Diversity Bioinformatics HPC” (BBSRC grant BB/ S019669/1)。
文摘An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascertain at early infection stages owing to the unfavourable transcript representation compared to the host genes.In this study,we compare two sequencing techniques,RNAseq and enrichment sequencing(RenSeq and PenSeq)of cDNA,to investigate gene expression patterns in the doubled monoploid potato(DM)infected with the late blight pathogen Phytophthora infestans.Our results reveal distinct advantages of cDNA RenSeq and PenSeq over traditional RNAseq in terms of target gene representation and transcriptional quantification at early infection stages.Throughout the infection time course,cDNA enrichment sequencing enables transcriptomic analyses for more targeted host and pathogen genes.For highly expressed genes that were sampled in parallel by both cDNA enrichment and RNAseq,a high level of concordance in expression profiles is observed,indicative of at least semi-quantitative gene expression representation following enrichment.
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
基金supported by the Institute for Basic Science (IBS-R022-D1)Global Learning&Academic Research Institution for Master’s/Ph D students and Post-Doc Program of the National Research Foundation of Korea Grant funded by the Ministry of Education (RS-2023-00301938)+1 种基金National Research Foundation of Korea Grant funded by the Korean government (RS-2024-00406152,MSIT)Additional financial support was provided by the 2024 Post-Doc Development Program of Pusan National University,Korea Medical Institute,and KREONET。
文摘Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.
基金funded by the South Oil Exploration and Development Company of PetroChina(2021-HNYJ-010).
文摘The Fushan Depression is one of the petroliferous depressions in the Beibuwan Basin,South China Sea.Previous studies have preliminarily explored the origin and source of crude oils in some areas of this depression.Nevertheless,no systematic investigations on the classification and origin of oils and hy-drocarbon migration processes have been made for the entire petroleum system in this depression,which has significantly hindered the hydrocarbon exploration in the region.A total of 32 mudstone and 58 oil samples from the Fushan Depression were analyzed to definite the detailed oil-source correlation within the sequence and sedimentary framework.The organic matter of third member of Paleogene Liushagang Formation(Els(3))source rocks,both deltaic and lacustrine mudstone,are algal-dominated with high abundance of C_(23)tricyclic terpane and C_(30)4-methylsteranes.The deltaic source rocks occur-ring in the first member(Els_(1))and second member(Els_(2))of the Paleogene Liushagang Formation are characterized by high abundance of C_(19+20)tricyclic terpane and oleanane,reflecting a more terrestrial plants contribution.While lacustrine source rocks of Els_(1)and Els_(2)display the reduced input of terrige-nous organic matter with relatively low abundance of C 19+20 tricyclic terpane and oleanane.Three types of oils were identified by their biomarker compositions in this study.Most of the oils discovered in the Huachang and Bailian Els_(1)reservoir belong to group A and were derived from lacustrine source rocks of Els_(1)and Els_(2).Group B oils are found within the Els_(1)and Els_(2)reservoirs,showing a close relation to the deltaic source rocks of Els_(1)and Els_(2),respectively.Group C oils,occurring in the Els3 reservoirs,have a good affinity with the Els3 source rocks.The spatial distribution and accumulation of different groups of oils are mainly controlled by the sedimentary facies and specific structural conditions.The Els_(2)reservoir in the Yong'an area belonging to Group B oil,are adjacent to the source kitchen and could be considered as the favorable exploration area in the future.
基金supported by the China Postdoctoral Science Foundation Grant(2023M734294)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202215)the National Natural Science Foundation of China(No.82001618).
文摘Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
基金Supported by the National Oncology Care Support Program,No.25000.056766/2015-64.
文摘BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.
