Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

A Flexible Capacitive Pressure Sensor with Adjustable Detection Range Based on the Inflatable Dielectric Layer for Human-Computer Interaction.

As an essential component in wearable electronic devices and intelligent robots, flexible pressure sensors have enormous application value in fields such as healthcare, human-computer interaction, and intelligent perception. However, due to the complex and ever-changing pressure loads borne by sensors in different application scenarios, this also puts great demands on the flexible response and adjustment ability of a sensor's detection range. Therefore, developing a flexible pressure sensor with a wide and adjustable detection range, which can be applied flexibly under different pressure loads, is also a major challenge in current research. In this paper, we propose a flexible pressure sensor with a wide and adjustable detection range based on an inflatable adjustable safety airbag as the dielectric layer. This sensor uses inflatable airbags prepared using 3D printing technology and silicone reverse molding technology as the dielectric layer and achieves high sensitivity (0.6 kPa-1 to 1.19 kPa-1), wide detection range (220-1500 kPa), and flexible performance applicability by adjusting the air pressure inside the dielectric layer. At the same time, its simple production process, convenient production, fast response time (100 ms), and good stability provide the possibility for the flexible application of sensors in different pressure detection. The experimental results indicate that the sensor has enormous potential for applications in wearable devices, healthcare, human-computer interaction, and intelligent perception recognition.

Enhancing mechanical and water barrier properties of starch film using chia mucilage.

Biodegradable packaging materials are increasingly being investigated due to rising concerns about food safety and environmental conservation. This study examines the incorporation of chia mucilage (CM) into starch-based films using the casting method, aiming to understand its effects on the structure and functionality of the films. CM, an anionic heteropolysaccharide, is hypothesized to enhance the mechanical and barrier properties of the films through polymer interactions and hydrogen bonding. Our findings confirm that CM incorporation results in films with uniformly smooth surfaces, indicating high compatibility and homogeneity within the starch matrix. Notably, CM improves film transparency and crystallinity. Mechanical assessments show a remarkable elevation in tensile strength, soaring from 5.21 MPa to 12.38 MPa, while elongation at break decreases from 61.73 % to 31.42 %, indicating a trade-off between strength and flexibility. Additionally, water solubility decreases from 57.97 % to 41.40 %, and water vapor permeability is reduced by 30 % with CM loading. These results highlight the role of CM in facilitating the formation of a dense, interconnected polymeric network within the starch matrix. Given the soluble dietary fiber nature of CM, the CS/CM (corn starch/chia mucilage) blended films are expected to be safe for food packaging and applicable as edible films with health benefits.

Chromene meroterpenoids from Rhododendron dauricum L. and their anti-inflammatory effects.

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.

An elastic single crystal composed of one-dimensional chiral coordination polymers.

A single crystal composed of one-dimensional coordinated polymers, [CdCl2(1-methyl-2-pyridone)]n, has been synthesized and characterized. This compound exhibits outstanding elastic bending due to the molecular spring nature of the CdCl2 coordination framework and weak intermolecular interactions between the coordination chains. Owing to the helical arrangement of organic ligands surrounding the coordination structure, the compound crystallizes in a chiral space group. As a result, it displays compelling circular dichroism spectra and second harmonic generation properties.

A Bayesian Change Point Model for Dynamic Alternative Transcription Start Site Usage During Cellular Differentiation.

ABSTRACT An alternative transcription start site (ATSS) is a major driving force for increasing the complexity of transcripts in human tissues. As a transcriptional regulatory mechanism, ATSS has biological significance. Many studies have confirmed that ATSS plays an important role in diseases and cell development and differentiation. However, exploration of its dynamic mechanisms remains insufficient. Identifying ATSS change points during cell differentiation is critical for elucidating potential dynamic mechanisms. For relative ATSS usage as percentage data, the existing methods lack sensitivity to detect the change point for ATSS longitudinal data. In addition, some methods have strict requirements for data distribution and cannot be applied to deal with this problem. In this study, the Bayesian change point detection model was first constructed using reparameterization techniques for two parameters of a beta distribution for the percentage data type, and the posterior distributions of parameters and change points were obtained using Markov Chain Monte Carlo (MCMC) sampling. With comprehensive simulation studies, the performance of the Bayesian change point detection model is found to be consistently powerful and robust across most scenarios with different sample sizes and beta distributions. Second, differential ATSS events in the real data, whose change points were identified using our method, were clustered according to their change points. Last, for each change point, pathway and transcription factor motif analyses were performed on its differential ATSS events. The results of our analyses demonstrated the effectiveness of the Bayesian change point detection model and provided biological insights into cell differentiation.

Fluorescence Sensors for the Detection of L-Histidine Based on Silver Nanoclusters Modulated by Copper Ions.

In this study, Cu2+ modulated silver nanoclusters were constructed for the turn-on, label-free detection of L-histidine. Six Ag NCs protected by oligonucleotides (DNA-Ag NCs) were tested in a series of experiments. Finally, A-DAN-Ag NCs were chosen as the best candidate due to their excellent fluorescent properties. The fluorescence of A-DAN-Ag NCs was quenched using Cu2+ through energy or electron transfer. However, quenched fluorescence could be restored dramatically in the presence of L-histidine due to Cu2+ liberation from A-DAN-Ag NCs and because of the chelation between the imidazole group of L-histidine and Cu2+. The proposed sensor exhibited high selectivity towards L-histidine over other amino acids, with a limit of detection (LOD) of 0.096 µM ranging from 0 to 8 µM. The proposed sensor succeeded in detecting L-histidine in diluted human urine. Therefore, the sensor has promising practical applications in biological systems.

Comprehensive analysis of immune-related lncRNAs in AML patients uncovers potential therapeutic targets and prognostic biomarkers.

Purpose: The objective of this study was to provide theoretically feasible strategies by understanding the relationship between the immune microenvironment and the diagnosis and prognosis of AML patients. To this end, we built a ceRNA network with lncRNAs as the core and analyzed the related lncRNAs in the immune microenvironment by bioinformatics analysis. Methods: AML transcriptome expression data and immune-related gene sets were obtained from TCGA and ImmPort. Utilizing Pearson correlation analysis, differentially expressed immune-related lncRNAs were identified. Then, the LASSO-Cox regression analysis was performed to generate a risk signature consisting immune-related lncRNAs. Accuracy of signature in predicting patient survival was evaluated using univariate and multivariate analysis. Next, GO and KEGG gene enrichment and ssGSEA were carried out for pathway enrichment analysis of 183 differentially expressed genes, followed by drug sensitivity and immune infiltration analysis with pRRophetic and CIBERSORT, respectively. Cytoscape was used to construct the ceRNA network for these lncRNAs. Results: 816 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by multivariate Cox and stepwise regression analysis contained 12 lncRNAs engaged in tumor apoptotic and metastatic processes: LINC02595, HCP5, AC020934.2, AC008770.3, LINC01770, AC092718.4, AL589863.1, AC131097.4, AC012368.1, C1RL-AS1, STARD4-AS1, and AC243960.1. Based on this predictive model, high-risk patients exhibited lower overall survival rates than low-risk patients. Signature lncRNAs showed significant correlation with tumor-infiltrating immune cells. In addition, significant differences in PD-1/PD-L1 expression and bleomycin/paclitaxel sensitivity were observed between risk groups. Conclusion: LncRNAs related to immune microenvironment were prospective prognostic and therapeutic options for AML.

Tetraphenylene-based semiconductive metal-organic framework crystals for direct X-ray detection and imaging.

MOFs have good potential for X-ray detection, but direct X-ray detection in single crystal form is rarely reported. In this work, we successfully synthesized Pb-TCPE, and the single crystal achieves a low detection limit and high detection sensitivity of 4812.6 µC Gyair-1 cm-2, which exhibits great potential for X-ray detection and imaging.

Targeted drug-loaded peptides induce tumor cell apoptosis and immunomodulation to increase antitumor efficacy.

Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells via the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue. In an acidic environment, DT/Pep1 transformed from spherical nanoparticles to aggregates with a high aspect ratio, which successfully extended the retention of the drugs in the tumor cells and bolstered the anticancer effect. In both in vivo and in vitro experiments, DT/Pep1 effectively blocked the cell cycle and induced apoptosis. Importantly, the DT/Pep1 system efficiently suppressed tumor development in mice bearing 4T1 tumors while simultaneously promoting immune system activation. Thus, the results of this study provide a system for breast cancer therapy and offer a novel and promising platform for peptide nanocarrier-based drug delivery.

[Exploring the Role of PCDHGB4 in the Occurrence of Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis].

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. METHODS: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes. RESULTS: Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways. CONCLUSIONS: The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population.

Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.

Improved bacterial composition and co-occurrence patterns of rhizosphere increased nutrient uptake and grain yield through cultivars mixtures in maize.

Crop diversification contributes to agricultural productivity and resources efficient utilization. However, whether cultivar mixtures in maize affects soil bacterial community, nutrient uptake, plant growth and yield remains unknown. A two-year lysimetric experiment was conducted using two maize cultivars (LY16 and JS501) with different root system architectures planted in monoculture or in mixture under normal fertilization (NF), reduced fertilization (RF) or no addition of fertilizer (CK) and was assessed at the silking stages. Cultivar mixtures and monoculture of LY16 had higher shoot biomass, nutrient uptake and total root length at silking stage, and grain yield than monoculture of JS501 under NF and RF conditions. Under NF and RF conditions, cultivar mixtures and monoculture of LY16 led to an increase in bacterial diversity, significant changes in community structure, and a high abundance of Bacteroidia and biomarkers of Chitinophagaceae and Saprospiraceae (Bacteroidia). Cultivar mixtures showed specific responses from modules of the rhizosphere bacterial community co-occurrence network, and the relative abundance of keystone taxa of cultivar mixtures was higher than that of monoculture of JS501. The keystone taxa had a broad and significant positive correlation with plant nutrient accumulation and grain yield. Cultivar mixtures showed similar assembly processes of Bacteroidia with monoculture of LY16, and the increased abundance of Chitinophagaceae may lead to a healthy rhizosphere bacterial community. Overall, our findings indicate that cultivar mixtures significantly affects the assembly and composition of the rhizosphere bacterial community, and thus benefits plant nutrient acquisition and plant growth. These findings could deepen our understanding of the facilitating effect of rhizosphere functional microbial community (e.g. plant nutrition uptake or immunity)of cultivar mixtures.

Drought decreases cotton fiber strength by altering sucrose flow route.

The potential mechanisms by which drought restricts cotton fiber cell wall synthesis and fiber strength are still not fully understood. Herein, drought experiments were conducted using two cultivars of upland cotton (Gossypium hirsutum), Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Results showed that drought notably reduced sucrose efflux from cottonseed coats to fibers by down-regulating the expression of GhSWEET10 and GhSWEET15 in outer cottonseed coats, leading to enhanced sucrose accumulation in cottonseed coats but decreased sucrose accumulation in fibers. Within cotton fibers, drought restricted the hydrolysis of sucrose to uridine-5'-diphosphoglucose by suppressing sucrose synthase activity, and drought favored the conversion of uridine-5'-diphosphoglucose to ß-1,3-glucan rather than cellulose by up-regulating GhCALS5. Hence, cellulose content was reduced, which was the main reason for the decreased fiber strength under drought. Moreover, drought promoted lignin synthesis by up-regulating the expression of Gh4CL4, GhPAL9, GhCCR5, GhCAD11, and GhCOMT6, which partly offset the negative influence of reduced cellulose content on fiber strength. Compared with Yuzaomian 9110, the drought-tolerance of Dexiamian 1 was evidenced by the following under drought conditions: (i) greater sucrose flow from seedcoat to fiber, (ii) less ß-1,3-glucan accumulation, and (iii) more lignin biosynthesis. Overall, this study provides new insights into the mechanism of reduced cotton fiber strength induced by drought.

The novel HLA-B*13:01:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*13:01:23 differs from HLA-B*13:01:01:01 by one nucleotide in exon 5.

Coumarins and flavones with anti-inflammatory activity isolated from the branches and leaves of Daphne retusa.

In this study, two new (1, 13) and fourteen known (2-12, 14-16) compounds were isolated from the branches and leaves of Daphne retusa. On the basis of chemical evidence and spectral data analysis (UV, ECD NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds have been tested for their inhibitory effects on NO production in LPS-induced RAW 264.7 cells, and compound 3 showed obvious inhibitory effect. Through target screening and molecular docking technology, potential binding targets for compound 3 to exert anti-inflammatory effects have been predicted.

Turn-on fluorescent nanoprobe for ATP detection based on DNA-templated silver nanoclusters.

A turn-on fluorescence nanoprobe was constructed for the determination of adenosine 5'-triphosphate (ATP) based on DNA-templated silver nanoclusters (DNA-AgNCs). The significant enhancement fluorescence intensity of DNA-AgNCs in the presence of ATP is due to the high special binding affinity between ATP and the aptamer, resulting in the environment of DNA-AgNCs with darkish fluorescence lying at one terminus of DNA slightly altering owing to the change of ATP aptamer conformation. A good linear range runs from 9 to 24 mM with a satisfactory detection limit of 3 µM. Furthermore, the proposed nanoprobe exhibited good performance for ATP detection in diluted fetal bovine serum.

Phenolics and terpenoids with good anti-inflammatory activity from the fruits of Amomum villosum and the anti-inflammatory mechanism of active diterpene.

The fruits of Amomum villosum are often considered a medicinal and food homologous material and have been found to have therapeutic effects in chronic enteritis, gastroenteritis, and duodenal ulcer. The aim of this study is to discover the anti-inflammatory active ingredients from dried ripe fruits of A. villosum and to elucidate the molecular mechanisms. We verified that the inhibitory activity of the ethyl acetate extract was superior to Dexamethasone (Dex), so we ultimately chose to study the ethyl acetate extract from the fruits of A. villosum. A total of 33 compounds were isolated from its ethyl acetate extract, including nine known diterpenoids (compounds 1-9), twelve known sesquiterpenoids (compounds 10-21), ten known phenolics (compounds 22, 23, 25-29, 31-33) and two new phenolics (24 and 30). On the basis of chemical evidences and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, HR-ESI-MS, NMR chemical shift calculations), the structures of new compounds were elucidated. Among these compounds, isocoronarin D (5) was found to have good anti-inflammatory activity. Further research has found that isocoronarin D can down-regulate the protein levels of COX2 and NOS2, activate Nrf2/Keap1 and suppress NF-κB signaling pathway in LPS-induced RAW264.7 cells. In addition, isocoronarin D inhibited inflammasome assembly during inflammasome activation by hampering the binding of NLRP3 and ASC. Further evidence revealed that isocoronarin D suppressed the assembly of the NLRP3 inflammasome via blocking the formation of ASC specks. From these results, isocoronarin D may be the important bioactive compound of A. villosum and exhibits anti-inflammatory effects by regulating the NF-κB/Nrf2/NLRP3 axis in macrophages.

METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control.

BACKGROUND: RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METHODS: METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC-MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. RESULTS: METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. CONCLUSIONS: Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.