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Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia. Effective delivery of drugs to bone marrow has potential for leukemia treatment. Here the authors report the delivery of chemotherapy drug Ara-C with HSPC cell membrane derived-biomimetic vesicles, which target leukemia stem cells thereby effectively inhibit its progression.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunction, motor abnormalities, and memory disorders, with a persistently high and rising incidence. The pathological features of AD include the extracellular deposition of the amyloid beta peptide (Aβ), the accumulation of neurofibrillary tangles (NFTs), and neuroinflammation. Microglia (MG), the main immune cells in the central nervous system (CNS), can transform into different phenotypes. An imbalance in their phenotypic transformation may induce neuroinflammation and lead to neurological diseases, playing a central role in the onset and progression of AD. This article aims to briefly review the key role of microglia-mediated neuroinflammation in the pathogenesis of AD and to summarize and analyze the strategies of traditional Chinese medicine (TCM) for targeting microglia in AD treatment. Literature review and analysis were conducted to summarize the role of microglia-mediated neuroinflammation in AD pathogenesis and to collate TCM therapeutic strategies aimed at modulating microglia. Microglia-mediated neuroinflammation plays a central role in the pathological progression of AD. TCM demonstrates potential in intervening in AD neuroinflammation by regulating the microglial phenotype and function. These related therapeutic strategies warrant further summary and analysis.

Leukemias are refractory hematological malignancies, characterized by marked intrinsic heterogeneity which poses significant obstacles to effective treatment. However, traditional bulk sequencing techniques have not been able to effectively unravel the heterogeneity among individual tumor cells. With the emergence of single-cell sequencing technology, it has bestowed upon us an unprecedented resolution to comprehend the mechanisms underlying leukemogenesis and drug resistance across various levels, including the genome, epigenome, transcriptome and proteome. Here, we provide an overview of the currently prevalent single-cell sequencing technologies and a detailed summary of single-cell studies conducted on leukemia, with a specific focus on four key aspects: (1) leukemia’s clonal architecture, (2) frameworks to determine leukemia subtypes, (3) tumor microenvironment (TME) and (4) the drug-resistant mechanisms of leukemia. This review provides a comprehensive summary of current single-cell studies on leukemia and highlights the markers and mechanisms that show promising clinical implications for the diagnosis and treatment of leukemia.

DNA methylation is a significant component in proximal chromatin regulation and plays crucial roles in regulating gene expression and maintaining the repressive state of retrotransposon elements. However, accurate profiling of the proteomics which simultaneously identifies specific DNA sequences and their associated epigenetic modifications remains a challenge. Here, we report a strategy termed SelectID ( sel ective profiling of e pigenetic c ontrol at genome t argets i dentified by d Cas9), which introduces methylated DNA binding domain into dCas9-mediated proximity labeling system to enable in situ protein capture at repetitive elements with 5-methylcytosine (5mC) modifications. SelectID is demonstrated as feasible as dCas9-TurboID system at specific DNA methylation regions, such as the chromosome 9 satellite. Using SelectID, we successfully identify CHD4 as potential repressors of methylated long interspersed nuclear element-1 (LINE-1) retrotransposon through direct binding at the 5’ untranslated region (5’UTR) of young LINE-1 elements. Overall, our SelectID approach has opened up avenues for uncovering potential regulators of specific DNA regions with DNA methylation, which will greatly facilitate future studies on epigenetic regulation. The authors introduce SelectID, an approach combining CRISPR-guided targeting with methylation-sensitive labeling to identify proteins interacting with methylated repetitive sequences. They suggest that CHD4 directly binds young LINE-1 retrotransposons, suppressing their activity.

The combined pollution of heavy metals and organic pollutants in water body has become one of vital environmental issues. Herein, a series of BiVO 4 /rGO/g-C 3 N 4 nanocomposites were synthesized for concurrent removals of organic pollutant and heavy metal. Results showed that using the optimized photocatalyst BiVO 4 /rGO/g-C 3 N 4 -28, tetracycline (TC) removal of 87.3% and copper (Cu (II)) removal of 90.6% were achieved under visible-light irradiation within 3 h, respectively; much higher than those using BiVO 4 and g-C 3 N 4 . More importantly, synergistic effect of TC and Cu (II) removals occurred on the surface of BiVO 4 /rGO/g-C 3 N 4 in the TC-Cu (II) coexistence condition. Additionally, the ·OH and ·O 2 ˉ were the most important active species for TC oxidation, while photogenerated electrons were the most responsible for Cu (II) reduction. Results of various characterizations and electron spin resonance test demonstrated that BiVO 4 /rGO/g-C 3 N 4 was a Z-scheme photocatalyst. Based on the identified intermediates, possible degradation pathways and mechanisms for photocatalytic degradation of TC were proposed. This study advances the development and mechanism of photocatalysts for collaborative removal of pollutants.

Bioretention cells (BCs) are widely used to manage urban runoff due to their positive impact on runoff control. Current research primarily focuses on optimizing the internal structural design of bioretention cells, while studies on the interactions between their spatial configuration, topography, and land use types are limited. This study employs the Storm Water Management Model (SWMM) and uses extreme rainfall to analyze the influence of typical stormwater flow paths, determined by various land use types and topography, as well as the spatial configurations of bioretention cells on catchment hydrological performance. The results show the following: (1) Different stormwater flow paths significantly affect catchment hydrological performance, with series-type pathways performing best. (2) The spatial configuration of bioretention cells significantly influences catchment hydrological performance. Decentralized BCs under series-type pathways showed better performance for reducing total outflow and peak runoff, with reduction rates increasing by 7.1% and 8.8%, while centralized BCs better delayed peak times. (3) Stormwater flow paths affect BC efficiency in catchment hydrological performance. Decentralized BCs under a series-type stormwater flow path are recommended for priority use. This study provides a novel perspective for optimizing the spatial arrangement of BCs and urban stormwater management, thereby contributing to flood risk mitigation.

Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French–American–British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists’ diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.

Biochar derived from sugarcane bagasse was prepared at different pyrolysis temperatures and holding times for adsorption of dimetridazole and metronidazole from aqueous solution. The optimal pyrolysis temperature and holding time were 500 °C and 120 min, respectively. The removal efficiencies of dimetridazole and metronidazole were 98.0% and 88.8%, respectively, at biochar dosage of 4.0 g L−1 and solution temperature of 30 °C. Kinetics data were fitted by four kinetics models, and results indicated that adsorption was governed by pseudo-second-order kinetics. Adsorption is a multi-step process that involves film diffusion and pore filling. In addition, five isotherm models were employed to describe the adsorption equilibrium. Brunauer–Emmett–Teller model presented better fitting for the adsorption equilibrium, and the maximum adsorption capacities were 72.17 and 23.61 mg g− 1 for dimetridazole and metronidazole, respectively. The calculated values of ΔG0 and ΔH0 indicated the non-spontaneous and exothermic nature of the adsorption process at the range of temperature studied. Thermodynamic studies also revealed that physical and chemical adsorptions were co-action. The adsorption mechanisms of dimetridazole and metronidazole onto biochar were mainly hydrogen bonding and π–π interaction. All the results revealed that sugarcane bagasse biochar can be used as alternative to costly adsorbents for the removal of dimetridazole and metronidazole from aqueous solution.