Energy field-based lane changing behavior interaction model and risk evaluation in the weaving section of expressway.

OBJECTIVE: With the development of intelligent driving assistance systems, the evaluation of driving behavior risk has shifted from traditional single-vehicle studies to multi-vehicle studies. This study aimed to investigate the interaction mechanism between vehicles and to study the microscopic laws of traffic flow operation. METHODS: Firstly, the concept of "driving interaction field" was proposed. The virtual interaction quality and distance were used to define the driving interaction field. The interaction angle distinguished the vehicle interaction between different lanes. Then, the risk mechanism in the interaction process was analyzed by driving risk index. Corresponding thresholds of 50% and 85% quantile values were determined. Finally, the process of the lane-changing simulation experiments was divided into three phases (preparation, execution and adjustment). RESULTS: The driving risk index of the execution phase was larger than the other phases. Meanwhile, the comparison with the classical driving risk indexes revealed that the proposed index was more accurate and intuitive in describing the interaction risks. CONCLUSIONS: The driving interaction model proposed in this study quantified the overall environmental pressure on the vehicle. It overcomes the previous limitation of kinetic interaction parameters. The research provides a new idea for the ITS and autonomous driving systems, contributing to the enhancement of traffic safety and efficiency.

Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models.

ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb repressive complex 2 (PRC2) to specific gene loci to repress transcription through trimethylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present. We discovered upregulation of lysine demethylase 6B (KDM6B), a demethylase for H3K27me3, in ASXL1-mutant leukemic cells, which further reduces H3K27me3 levels and facilitates myeloid transformation. Here, we demonstrated that heterozygous deletion of Kdm6b restored H3K27me3 levels and normalized dysregulated gene expression in Asxl1Y588XTg hematopoietic stem/progenitor cells (HSPCs). Furthermore, heterozygous deletion of Kdm6b decreased the HSPC pool, restored their self-renewal capacity, prevented biased myeloid differentiation, and abrogated progression to myeloid malignancies in Asxl1Y588XTg mice. Importantly, administration of GSK-J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1-mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations.

ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMAs) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5- AZA could also extend the rationale of this treatment concept to high-risk MDS. In this study, we performed a comprehensive in vitro assessment of alvocidib and 5-AZA effects in n=45 high-risk MDS patients. Our data revealed additive cytotoxic effects of the combination treatment. Mutational profiling of MDS samples identified ASXL1 mutations as predictors of response. Further, increased response rates were associated with higher gene-expression of the pro-apoptotic factor NOXA in ASXL1 mutated samples. The higher sensitivity of ASXL1 mutant cells to the combination treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies.

Loss of BRD4 induces cell senescence in HSC/HPCs by deregulating histone H3 clipping.

Bromodomain-containing protein 4 (BRD4) is overexpressed and functionally implicated in various myeloid malignancies. However, the role of BRD4 in normal hematopoiesis remains largely unknown. Here, utilizing an inducible Brd4 knockout mouse model, we find that deletion of Brd4 (Brd4Δ/Δ ) in the hematopoietic system impairs hematopoietic stem cell (HSC) self-renewal and differentiation, which associates with cell cycle arrest and senescence. ATAC-seq analysis shows increased chromatin accessibility in Brd4Δ/Δ hematopoietic stem/progenitor cells (HSC/HPCs). Genome-wide mapping with cleavage under target and release using nuclease (CUT&RUN) assays demonstrate that increased global enrichment of H3K122ac and H3K4me3 in Brd4Δ/Δ HSC/HPCs is associated with the upregulation of senescence-specific genes. Interestingly, Brd4 deletion increases clipped H3 (cH3) which correlates with the upregulation of senescence-specific genes and results in a higher frequency of senescent HSC/HPCs. Re-expression of BRD4 reduces cH3 levels and rescues the senescence rate in Brd4Δ/Δ HSC/HPCs. This study unveils an important role of BRD4 in HSC/HPC function by preventing H3 clipping and suppressing senescence gene expression.

Effects of digital psychotherapy for depression and anxiety: A systematic review and bayesian network meta-analysis.

OBJECTIVE: To evaluate the effectiveness of digital psychotherapies for depression and anxiety. We conducted a systematic review and network meta-analyses (NMA) to make comparisons of digital psychotherapies. METHODS: A bayesian NMA was conducted in this study. The databases including PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials and CINAL were searched for all eligible randomized controlled trials (RCTs) published from Jan 1, 2012 to Oct 1, 2022. We used the Cochrane Collaboration's Risk of bias tool for quality assessment. The primary outcomes were set as a standardized mean difference model in efficacy to describe continuous outcomes. We used STATA and WinBUGS to conduct a bayesian network meta-analysis of all interventions based on a random-effects model. This study was registered with PROSPERO, number CRD42022374558. RESULTS: From the retrieved 16,750 publications, we included 72 RCTs (13,096 participants) with the overall medium quality and above. In terms of depression scale, cognitive behavioral therapy (CBT) was more effective than TAU (SMDs 0.53) and NT (SMDs 0.98). In terms of anxiety scale, CBT (SMDs 0.68; SMDs 0.72) and exercise therapy (ERT) (SMDs 1.01; SMDs 1.05) were more effective than TAU and NT. LIMITATIONS: Uneven quality of literature, simple network, and subjective judgment. CONCLUSION: Based on NMA results, we suggest that CBT, which is the most commonly used digital technology, should be preferred among digital psychotherapy for relieving depression and anxiety symptoms. Digital exercise therapy is an effective strategy to relieve some anxiety problems in the context of COVID-19.

Epigenetic regulation by ASXL1 in myeloid malignancies.

Myeloid malignancies are clonal hematopoietic disorders that are comprised of a spectrum of genetically heterogeneous disorders, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Myeloid malignancies are characterized by excessive proliferation, abnormal self-renewal, and/or differentiation defects of hematopoietic stem cells (HSCs) and myeloid progenitor cells hematopoietic stem/progenitor cells (HSPCs). Myeloid malignancies can be caused by genetic and epigenetic alterations that provoke key cellular functions, such as self-renewal, proliferation, biased lineage commitment, and differentiation. Advances in next-generation sequencing led to the identification of multiple mutations in myeloid neoplasms, and many new gene mutations were identified as key factors in driving the pathogenesis of myeloid malignancies. The polycomb protein ASXL1 was identified to be frequently mutated in all forms of myeloid malignancies, with mutational frequencies of 20%, 43%, 10%, and 20% in MDS, CMML, MPN, and AML, respectively. Significantly, ASXL1 mutations are associated with a poor prognosis in all forms of myeloid malignancies. The fact that ASXL1 mutations are associated with poor prognosis in patients with CMML, MDS, and AML, points to the possibility that ASXL1 mutation is a key factor in the development of myeloid malignancies. This review summarizes the recent advances in understanding myeloid malignancies with a specific focus on ASXL1 mutations.

Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1.

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/-) male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of microRNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male HSCs, thus abrogating the functional effect of Lxn in male HSCs and hematopoiesis. These findings uncover a regulatory mechanism involving a sex-chromosome-related microRNA and its differential control of Lxn-Thbs1 signaling in hematopoiesis and shed light on the process underlying sex dimorphism in both normal and malignant hematopoiesis.

Antibiotic pollution of the Yellow River in China and its relationship with dissolved organic matter: Distribution and Source identification.

Understanding the sources of antibiotics is important for managing antibiotic contamination and preventing environmental risks in the aquatic environment. In this study, the distribution of dissolved organic matter (DOM) and 24 antibiotics from four typical classes (quinolones, macrolides, sulfonamides and tetracyclines) in the Yellow River basin containing distinct sources of pollution was investigated. In particular, relationships between the antibiotic concentrations and fluorescent properties of DOM were to be established to identify antibiotic sources. A total of 22 antibiotics were detected, with maximum concentrations ranging from 0.27 to 30.14 ng/L in the mainstream of the Yellow River. Of these antibiotics, only erythromycin (ERY) and sulfamethoxazole (SMX) posed potential risks to aquatic organisms. Spatially, tetracyclines were mainly distributed in the upstream reaches of the river, and quinolones were largely distributed in the midstream. High levels of sulfonamides were present downstream of the investigated river. Only EYR belonging to the macrolide group was detected and had a high downstream concentration. EEM-PARAFAC analysis showed that DOM was composed of visible fulvic acid-like fluorescence fraction (C1), ultraviolet fulvic acid-like fluorescence fraction (C2) and protein-like fraction (C3). Using Pearson correlation analysis, this study demonstrated a close relationship between DOM spectral parameters and antibiotic concentrations in the Yellow River basin. Specifically, r (C3, C2) was significantly and positively correlated with the concentrations of SMX, sulfadoxine (SDX), and ERY, while humification index (HIX) had an opposite relationship with these antibiotics. These results suggested that SMX, SDX and ERY were mainly discharged from wastewater treatment plants into the mainstream of the Yellow River. This work provides a powerful demonstration that DOM plays an important role in indicating the occurrence and sources of antibiotics in the aquatic environment.

Development and Assessment of Assisted Diagnosis Models Using Machine Learning for Identifying Elderly Patients With Malnutrition: Cohort Study.

BACKGROUND: Older patients are at an increased risk of malnutrition due to many factors related to poor clinical outcomes. OBJECTIVE: This study aims to develop an assisted diagnosis model using machine learning (ML) for identifying older patients with malnutrition and providing the focus of individualized treatment. METHODS: We reanalyzed a multicenter, observational cohort study including 2660 older patients. Baseline malnutrition was defined using the global leadership initiative on malnutrition (GLIM) criteria, and the study population was randomly divided into a derivation group (2128/2660, 80%) and a validation group (532/2660, 20%). We applied 5 ML algorithms and further explored the relationship between features and the risk of malnutrition by using the Shapley additive explanations visualization method. RESULTS: The proposed ML models were capable to identify older patients with malnutrition. In the external validation cohort, the top 3 models by the area under the receiver operating characteristic curve were light gradient boosting machine (92.1%), extreme gradient boosting (91.9%), and the random forest model (91.5%). Additionally, the analysis of the importance of features revealed that BMI, weight loss, and calf circumference were the strongest predictors to affect GLIM. A BMI of below 21 kg/m2 was associated with a higher risk of GLIM in older people. CONCLUSIONS: We developed ML models for assisting diagnosis of malnutrition based on the GLIM criteria. The cutoff values of laboratory tests generated by Shapley additive explanations could provide references for the identification of malnutrition. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-EPC-14005253; https://www.chictr.org.cn/showproj.aspx?proj=9542.

TWAS Atlas: a curated knowledgebase of transcriptome-wide association studies.

Transcriptome-wide association studies (TWASs), as a practical and prevalent approach for detecting the associations between genetically regulated genes and traits, are now leading to a better understanding of the complex mechanisms of genetic variants in regulating various diseases and traits. Despite the ever-increasing TWAS outputs, there is still a lack of databases curating massive public TWAS information and knowledge. To fill this gap, here we present TWAS Atlas (https://ngdc.cncb.ac.cn/twas/), an integrated knowledgebase of TWAS findings manually curated from extensive literature. In the current implementation, TWAS Atlas collects 401,266 high-quality human gene-trait associations from 200 publications, covering 22,247 genes and 257 traits across 135 tissue types. In particular, an interactive knowledge graph of the collected gene-trait associations is constructed together with single nucleotide polymorphism (SNP)-gene associations to build up comprehensive regulatory networks at multi-omics levels. In addition, TWAS Atlas, as a user-friendly web interface, efficiently enables users to browse, search and download all association information, relevant research metadata and annotation information of interest. Taken together, TWAS Atlas is of great value for promoting the utility and availability of TWAS results in explaining the complex genetic basis as well as providing new insights for human health and disease research.

Quantifying Concentrations and Emissions of Hexachlorobutadiene - A New Atmospheric Persistent Organic Pollutant in northern China.

Hexachlorobutadiene (HCBD) was listed as a new persistent organic pollutant for global regulation under Stockholm Convention in 2015, and there has been scarce information on its atmospheric concentrations, distributions, and emission sources. HCBD air samples were collected and analyzed to characterize concentrations and distributions at high elevation and urban sites as well as emission source locations in Northern China. We found ambient concentrations of HCBD in Northern China averaged at 34 ± 16 and 36 ± 28 pptv at urban sites in Jinan and Tai'an, respectively, and 31 ± 21 pptv at a high-elevation site Mount Tai. HCBD concentrations at the high elevation and urban sites were found to be affected by long-range transport under the influence of the East Asian monsoon climate. Over potential sources areas, we found concentrations of 76 ± 33 pptv in a mixed factory park, 59 ± 21 pptv in a rubber plant and 74 ± 8 pptv in a municipal solid waste (MSW) landfill area, which were all several times higher than in urban sites. The large concentration gradient across the various environments revealed strong emission sources of HCBD, especially over MSW landfill and Cl-compound production and application areas. An emission rate of 9.2 × 104 kg/yr and an oxidation rate of 32.9 kg/yr for HCBD were estimated for the mixed factory park. OH and Cl are much more active in reaction with HCBD than other oxidants in the atmosphere. Dry deposition and oxidation removed about 5.3% and 0.04%, respectively, of the emitted, suggesting that ∼95% of the emitted HCBD remaining in the atmosphere and could be transported for redistribution. Our findings revealed significant emission sources of HCBD in northern China, which was in turn affected by major sources in East-central China. The regional influence of HCBD pollution warrants serious concerns and points to the need to develop mitigation strategies.

The Role of PHF6 in Hematopoiesis and Hematologic Malignancies.

Epigenetic regulation of gene expression represents an important mechanism in the maintenance of stem cell function. Alterations in epigenetic regulation contribute to the pathogenesis of hematological malignancies. Plant homeodomain finger protein 6 (PHF6) is a member of the plant homeodomain (PHD)-like zinc finger family of proteins that is involved in transcriptional regulation through the modification of the chromatin state. Germline mutation of PHF6 is the causative genetic alteration of the X-linked mental retardation Borjeson-Forssman-Lehmann syndrome (BFLS). Somatic mutations in PHF6 are identified in human leukemia, such as adult T-cell acute lymphoblastic leukemia (T-ALL, ~ 38%), pediatric T-ALL (~ 16%), acute myeloid leukemia (AML, ~ 3%), chronic myeloid leukemia (CML, ~ 2.5%), mixed phenotype acute leukemia (MPAL, ~ 20%), and high-grade B-cell lymphoma (HGBCL, ~ 3%). More recent studies imply an oncogenic effect of PHF6 in B-cell acute lymphoblastic leukemia (B-ALL) and solid tumors. These data demonstrate that PHF6 could act as a double-edged sword, either a tumor suppressor or an oncogene, in a lineage-dependent manner. However, the underlying mechanisms of PHF6 in normal hematopoiesis and leukemogenesis remain largely unknown. In this review, we summarize current knowledge of PHF6, emphasizing the role of PHF6 in hematological malignancies. Epigenetic regulation of PHF6 in B-ALL. PHF6 maintains a chromatin structure that is permissive to B-cell identity genes, but not T-cell-specific genes (left). Loss of PHF6 leads to aberrant expression of B-cell- and T-cell-specific genes resulting from lineage promiscuity and binding of T-cell transcription factors (right).

Core-shell structured Co3O4@PPy composite for electrochemical determination of terbutylhydroquinone.

TBHQ is a significant synthetic antioxidant, but excessive use of TBHQ is harmful to human health. Therefore, the preparation of a high-efficiency TBHQ electrochemical sensor is of great significance. In this work, a core-shell structured Co3O4@PPy composite is synthesized for TBHQ determination and exhibits remarkable electrochemical properties. The core-shell structure of Co3O4@PPy composite shows the synergistic effects of fast charge transfer, rich active surface area and more active sites. Under optimal conditions, the linear range of the developed sensor is 0.2-600 µM, and the detection limit is 0.05 µM (S/N = 3). In addition, it also has good stability and reproducibility due to the stable protective role of the PPy shell. The proposed sensor can also be applied to practical sample detection.

ASXL1/2 mutations and myeloid malignancies.

Myeloid malignancies develop through the accumulation of genetic and epigenetic alterations that dysregulate hematopoietic stem cell (HSC) self-renewal, stimulate HSC proliferation and result in differentiation defects. The polycomb group (PcG) and trithorax group (TrxG) of epigenetic regulators act antagonistically to regulate the expression of genes key to stem cell functions. The genes encoding these proteins, and the proteins that interact with them or affect their occupancy at chromatin, are frequently mutated in myeloid malignancies. PcG and TrxG proteins are regulated by Enhancers of Trithorax and Polycomb (ETP) proteins. ASXL1 and ASXL2 are ETP proteins that assemble chromatin modification complexes and transcription factors. ASXL1 mutations frequently occur in myeloid malignancies and are associated with a poor prognosis, whereas ASXL2 mutations frequently occur in AML with t(8;21)/RUNX1-RUNX1T1 and less frequently in other subtypes of myeloid malignancies. Herein, we review the role of ASXL1 and ASXL2 in normal and malignant hematopoiesis by summarizing the findings of mouse model systems and discussing their underlying molecular mechanisms.

Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor.

BACKGROUND: IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors. METHOD: In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves. RESULTS: Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma. CONCLUSION: This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.

HOTTIP-dependent R-loop formation regulates CTCF boundary activity and TAD integrity in leukemia.

HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) driven by MLL rearrangements or NPM1 mutations to mediate HOXA topologically associated domain (TAD) formation and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CCCTC-binding factor (CTCF) chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly interacts with and regulates a fraction of CTCF-binding sites (CBSs) in the AML genome by recruiting CTCF/cohesin complex and R-loop-associated regulators to form R-loops. HOTTIP-mediated R-loops reinforce the CTCF boundary and facilitate formation of TADs to drive gene transcription. Either deleting CBS or targeting RNase H to eliminate R-loops in the boundary CBS of ß-catenin TAD impaired CTCF boundary activity, inhibited promoter/enhancer interactions, reduced ß-catenin target expression, and mitigated leukemogenesis in xenograft mouse models with aberrant HOTTIP expression. Thus, HOTTIP-mediated R-loop formation directly reinforces CTCF chromatin boundary activity and TAD integrity to drive oncogene transcription and leukemia development.

How fern and fern allies respond to heterogeneous habitat - a case in Yuanjiang dry-hot valley.

The Yuanjiang dry-hot valley features hot and dry climate, low vegetation and soil degradation. It had lush vegetation in the past, but has become degraded in recent decades. Understanding the interrelationship between species and the habitat is necessary to explain this change. In this study, a link between fern and fern allies - a group that is hypersensitive to environmental factors and their circumstances is constructed. Intensive transects and plots were designed to be proxies for extant fern and fern allies, and their habitats. Fifty years of meteorological records of precipitation and temperature along altitude and river running direction (latitudinal) were employed. Alpha and beta diversity are used to access diversity. Species_estimated, Singletons, Uniques, ACE, ICE, and Chao2, which associate to abundance and rarity, are subscribed to the correlation between fern and fern allies, and their ecosystem. Eight species, Selaginella pseudopaleifera, Aleuritopteris squamosa, Adiantum malesianum, Pteris vittata, Davallia trichomanoides, Sinephropteris delavayi, Selaginella jugorum, and Lygodium japonicum are used as indicators of a typical xeric and sun-drying habitat. The results indicate (1) accompanied by dramatically shrinking habitats, fern and fern allies are in very low diversity and abundance, whereas the rarity is relatively high; (2) for fern and fern allies, environmental factors are positive when altitude goes up; and (3) eight indicator species are latitudinally correlated with fern and fern allies along the river running direction.

A poly(3,4-ethylenedioxythiophene)/carbon nanotube hybrid film for electrocatalytic determination of tertiary butylhydroquinone.

The preparation of ideal sensing materials is of great significance for the realization of high-performance electrochemical analysis. However, in previous methods, most electrode materials are firstly synthesized and dispersed, finally dropped on the electrode surface, which led to complicated operation and poor adhesion between the materials and electrode surface. In this study, a PEDOT-CNT hybrid film has been prepared by combining carboxylated carbon nanotubes as dopants with PEDOT through scalable and easy-to-operate electrochemical deposition. The PEDOT-CNT modified electrode shows excellent performance for the determination of tertiary butylhydroquinone, with a wide linear range of 0.5-820 µM, a low detection limit of 0.12 µM, high stability and reproducibility. In addition, the mechanism of electrodeposition of CNTs and tertiary butylhydroquinone has also been discussed briefly. The PEDOT-CNT hybrid film possesses the preeminent sensing capacity in monitoring tertiary butylhydroquinone, providing research clues for the design and development of new electrode materials in the future.

p300 suppresses the transition of myelodysplastic syndromes to acute myeloid leukemia.

Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.