Synchronous T-cell lymphoblastic lymphoma, chronic myelomonocytic leukemia and myeloma with sequential acute myeloid leukemia transformation.
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Letter↗
Biomedical subjects
Ke Xu
Publications and source records attributed to Ke Xu.
An intricate functional relationship between NuA4 and Sfp1 regulates ribosome biogenesis in response to nutrient availability.
Ribosome biogenesis is a crucial process requiring enormous transcriptional output. In budding yeast, the expression of 138 ribosomal protein (RP) genes and over 200 ribosome biogenesis (RiBi) genes is regulated by an intricate network of factors, including the nutrient-sensitive transcription activator Sfp1 and the NuA4 coactivator/acetyltransferase complex. Nutrient starvation or inhibition of target of rapamycin complex 1 by rapamycin leads to repression of RP and RiBi genes, in part through blocking Sfp1 nuclear localization and NuA4-dependent chromatin acetylation. Here, we demonstrate that Sfp1 physically interacts with NuA4 in a target of rapamycin complex 1-dependent manner. Our results indicate that Sfp1, along with NuA4, regulate the transcription of RiBi and RP genes via distinct mechanisms depending on promoter architectures. Sfp1 promotes histone acetylation at the promoters without affecting NuA4 recruitment. In contrast, NuA4 does impact Sfp1 binding but specifically at two classes of RP genes. Importantly, NuA4 acetylates Sfp1 at lysines 655 and 657, regulating its function. Cells expressing Sfp1 with acetyl-mimicking mutations exhibit increased expression of RiBi genes while RP genes remain stable. However, the same mutants lead to the loss of Sfp1 binding/activity at RiBi genes when cells are under non-optimal growth conditions. Mimicking constitutive acetylation of Sfp1 also limits the transcriptional burst of RP genes upon addition of glucose. Altogether, these results draw an intricate functional relationship between Sfp1 and NuA4 to control ribosome biogenesis, fine-tuning transcription output in different growth conditions.
Saccharomyces cerevisiae Proteins↗
High-Purity Monovalent Functionalization of Carbon Nanotubes.
Single-walled carbon nanotubes (SWCNTs) show promise for probing molecular interactions at single-molecule resolution, yet generating SWCNT populations bearing a single defined functional tag remains challenging because surface functionalization is inherently stochastic. Here, we present a batch-scale strategy to produce predominantly singly tagged SWCNTs by leveraging the stochastic adsorption of single-stranded DNA (ssDNA). Specifically, SWCNTs are dispersed using a mixture of unmodified ssDNA (um-ssDNA) and a minor fraction of modified ssDNA (m-ssDNA) carrying an affinity handle. We developed a probabilistic ssDNA-SWCNT binding model that predicts the distribution of m-ssDNA per nanotube as a function of the input minor-strand fraction p = m-ssDNA/total ssDNA, enabling selection of conditions that maximize single-tag purity. Using magnetic-bead capture via a biotin affinity interaction and subsequent release, we isolate SWCNTs with 97.6% predicted single-tag purity at 2% recovery. Single-molecule fluorescence imaging further supports predominantly single-label occupancy under the model-selected conditions. Thus, this approach provides a general route to SWCNTs bearing a single molecular handle for downstream conjugation and assembly, supporting diverse future applications in SWCNT-based nanotechnologies.
Nanotubes, Carbon↗
stDyer-image improves clustering analysis of spatially resolved transcriptomics and proteomics with morphological images.
MOTIVATION: Spatially resolved transcriptomics (SRT) and spatially resolved proteomics (SRP) data enable the study of gene expression and protein abundances within their precise spatial and cellular contexts in tissues. Certain SRT and SRP technologies also capture corresponding morphology images, adding another layer of valuable information. However, few existing methods developed for SRT data effectively leverage these supplementary images to enhance clustering performance. RESULTS: Here, we introduce stDyer-image, an end-to-end deep learning framework designed for clustering for SRT and SRP datasets with images. Unlike existing methods that utilize images to complement gene expression data, stDyer-image directly links image features to cluster labels. This approach draws inspiration from pathologists, who can visually identify specific cell types or tumor regions from morphological images without relying on gene expression or protein abundances. Benchmarks against state-of-the-art tools demonstrate that stDyer-image achieves superior performance in clustering. Moreover, it is capable of handling large-scale datasets across diverse technologies, making it a versatile and powerful tool for spatial omics analysis. AVAILABILITY AND IMPLEMENTATION: The source code of stDyer-image and detailed tutorials are available at https://github.com/ericcombiolab/stDyer-image.
Proteomics↗
Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review.
Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.
Humans↗
Putative function and prognostic molecular marker of mast cells in colorectal cancer.
BACKGROUND: The increased demand for markers for colorectal cancer (CRC) highlights the importance of investigating immune cells involved in CRC progression. This study aims to dissect the mast cells in CRC, characterize the role of mast cells in CRC development, coordinate molecular communication between mast cells and malignant cells, and construct and validate a prognostic classification model based on mast cell markers. METHODS: Single-cell transcriptome data of CRC patients were extracted from GSE146771 for cell classification and annotation. The malignant cells were identified by copykat and the communication between mast cells and malignant cells was analyzed by CellChat. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis of mast cell markers were performed in the TCGA-COAD cohort to construct a prognostic classification model. qRT-PCR was performed to detect the mRNA expression of the molecules in the classification model in P815 and MC-9 cells. The co-culture experiment of MC38 and P815 cells were performed in 12-well transwell dish. Wound healing assay and Transwell assay were performed to detect cell migration and invasion. RESULTS: 10,186 high-quality cells in GSE146771 were annotated to 9 cell types. Six markers in mast cells (HDC, GATA2, ASAH1, BTBD19, TIMP1, FAM110A) were selected to construct a classification model. The high-risk score defined showed high infiltration of immunosuppressive cells, including endothelial cells, CAFs, Tregs and high angiogenesis and epithelial-mesenchymal transition (EMT) activities. In the model, HDC were abnormally low expressed in P815 cells, while BTBD19, FAM110A, GATA2, ASAH1 and TIMP1 showed excessive expression in P815 cells. Knockdown of GATA2 in the co-culture system of P815 and MC38 cells blocked cell migration and invasion. CONCLUSION: This study identified the cell types within CRC, elaborated the cellular functions of mast cells in CRC development and their molecular communication to coordinate malignant cells, and highlighted the molecular components and biological features that constitute promising prognostic classification model.
Mast Cells↗
Aberrant DNA methylation of genes regulating CD4+ T cell HIV-1 reservoir in women with HIV.
BACKGROUND: The HIV-1 reservoir in CD4+ T cells (HRCD4) pose a major challenge to curing HIV, with many of its mechanisms still unclear. HIV-1 DNA integration and immune responses may alter the host's epigenetic landscape, potentially silencing HIV-1 replication. METHODS: This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HRCD4. RESULTS: The average total HRCD4 size was 1409 copies per million cells, with most proviruses defective and only a small proportion intact. The study identified 245 differentially methylated CpG sites and 85 regions linked to HRCD4 size, with 52% of significant sites in intronic regions. Genes associated with HRCD4 were involved in viral replication, HIV-1 latency and cell growth and apoptosis. HRCD4 size was inversely related to DNA methylation of interferon signalling genes and positively associated with methylation at known HIV-1 integration sites. HRCD4-associated genes were enriched on the pathways related to immune defence, transcription repression and host-virus interactions. CONCLUSIONS: These findings suggest that HIV-1 reservoir is linked to aberrant DNA methylation in CD4+ T cells, offering new insights into epigenetic mechanisms of HIV-1 latency and potential molecular targets for eradication strategies. KEY POINTS: Study involved 427 women with HIV. Identified 245 aberrant DNA methylation sites and 85 methylation regions in CD4+ T cells linked to the HIV-1 reservoir. Highlighted genes are involved in viral replication, immune defence, and host genome integration. Findings suggest potential molecular targets for eradication strategies.
Humans↗
Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.
Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (ncombined = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD.
Humans↗
Diplotypes of the human serotonin 1B receptor promoter predict growth hormone responses to sumatriptan in abstinent alcohol-dependent men.
BACKGROUND: Some studies have associated alcohol dependence (AD) with the human serotonin (5-HT)(1B) receptor (HTR1B). This investigation explored the functional responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while measuring genetic heterogeneity in the HTR1B promoter. METHODS: Abstinent AD men (n = 27) and abstinent men without any alcohol use disorder (n = 19) were administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples collected over the following 2 hours were assayed for growth hormone (GH) concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of the HTR1B promoter and diplotypes determined. RESULTS: Integrated GH responses were predicted by interactions of AD and promoter diplotypes, as well as subject ethnicity. The final model accounted for nearly 35% of the variance in GH responses. Post hoc evaluation revealed that AD was associated with a blunting of GH secretion only among individuals with the most common HTR1B diplotype (TT/TT). CONCLUSIONS: A blunting of GH responses in abstinent AD men was observed only among those with the most common HTR1B promoter diplotype. Less common promoter diplotypes appeared protective. Controlling for genetic background is a useful augmentation of case-control pharmacological challenge strategies designed to elucidate the psychobiology of AD and other complex disorders.
Adult↗
Demand for private health insurance in Chinese urban areas.
Between 1993 and 2003, the proportion of urban residents without health insurance rose from 27 to 50%. The probability of outpatient visits in the previous 2 weeks dropped from 19.9 to 11.8% in urban areas between 1993 and 2003, and from 16.0 to 13.9% in rural areas. To improve risk-pooling and risk-sharing, private health insurance should play an important role in China's health insurance system. This paper estimates the demand for private health insurance in urban areas using contingent valuation methods. Individuals were asked about their willingness-to-pay (WTP) for major catastrophic disease insurance (MCDI), inpatient expenses insurance (IEI), and outpatient expenses insurance (OEI). The study was based on a household survey conducted in four small cities in China in 2004 and included 2671 respondents. More people would like to buy IEI and MCDI (48.5 and 43.0%, respectively) than OEI (24.5%). In addition, individuals would pay a higher premium for MCDI and IEI than for OEI. The price elasticities of demand for MCDI, IEI, and OEI were -0.27, -0.34, and -0.42, respectively. The determinants of enrollment in the three private health insurance programs were similar with employment status, age, education, and income.
Adult↗
Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children.
OBJECTIVE: The study aimed to determine the cognitive effect of the Val108/158Met polymorphism in the catechol-O-methyltransferase (COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. METHOD: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function--including working memory, verbal and motor inhibition, attentional control, and IQ--were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. RESULTS: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. CONCLUSIONS: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.
Adolescent↗
Emergency endovascular repair of iliac artery rupture caused by post-stenting angioplasty with an endograft.
Iliac artery rupture is a rare complication of post-stenting angioplasty and can lead to massive life-threatening haemorrhage. Conventional surgery can not repair the damaged vessel easily and may cause substantial blood loss and high operative morbidity and mortality. We report our experience with a self-expanding covered endoprosthesis for endovascular repair of the rupture of an iliac artery caused by stenting angioplasty.
Aged, 80 and over↗
Detecting changes in financial protection: creating evidence for policy in Estonia.
Ninety-four per cent of the Estonian population is covered by public health insurance, but private expenditure has been increasing quickly both in real terms and as a percentage of total health expenditure. To date, little attention has been given to the impact this could have on the population's financial protection. Out-of-pocket payments, which account for the bulk of the private expenditure in many low- and middle-income countries, can push people into poverty and more generally represent too high a burden for some households. It is therefore very important that governments monitor the impact of out-of-pocket payments on health. Using an example from Estonia, this paper aims to illustrate that, if household budget survey data are available, monitoring a population's financial protection is not a complex undertaking. Further, by combining simple statistical analyses of these data with a good knowledge of a country's health system, it is possible to give a fairly detailed diagnostic of the nature of the population's coverage limitation. This allows for the presentation of easily interpretable results that can raise awareness among policy-makers and help to target adequate policy responses. Using Estonian household budget surveys from 1995, 2001 and 2002, we show that the proportion of households who spend more than 20% of their capacity to pay on health increased from 3.4% in 1995 to 7.4% in 2002 and that in 2002, 1.3% of the population fell into poverty because of health payments. Logistic regression helps in identifying the population most at risk: elderly patients who belong to poor households and spend high amounts on medicines. This study, which can be replicated, did raise awareness among policy-makers about the changes in financial protection over the years in Estonia.
Data Collection↗
Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.
Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.
Animals↗
Fabrication of Cd(OH)2 nanorings by ultrasonic chiselling on Cd(OH)2 nanoplates.
Cd(OH)2 nanorings were successfully fabricated from Cd(OH)2 nanoplates by ultrasonic chiselling, a unique effect of the sonochemical process that has never been reported before.
Journal Article↗
ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein.
Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factor-like repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.
ADAM Proteins↗
ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.
Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.
ADAM Proteins↗
Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder.
A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The L(G) allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and L(G) alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function L(A)L(A) genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The L(A) allele was twofold overtransmitted to the patients with OCD. The HTTLPR L(A)L(A) genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
Adult↗