A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells.

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

Deubiquitinase USP9X stabilizes RNA m6A demethylase ALKBH5 and promotes acute myeloid leukemia cell survival.

Post-translational modifications including protein ubiquitination regulate a plethora of cellular processes in distinct manners. RNA N6-methyladenosine is the most abundant post-transcriptional modification on mammalian mRNAs and plays important roles in various physiological and pathological conditions including hematologic malignancies. We previously determined that the RNA N6-methyladenosine eraser ALKBH5 is necessary for the maintenance of acute myeloid leukemia (AML) stem cell function, but the post-translational modifications involved in ALKBH5 regulation remain elusive. Here, we show that deubiquitinase ubiquitin-specific peptidase 9X (USP9X) stabilizes ALKBH5 and promotes AML cell survival. Through the use of mass spectrometry as an unbiased approach, we identify USP9X and confirm that it directly binds to ALKBH5. USP9X stabilizes ALKBH5 by removing the K48-linked polyubiquitin chain at K57. Using human myeloid leukemia cells and a murine AML model, we find that genetic knockdown or pharmaceutical inhibition of USP9X inhibits leukemia cell proliferation, induces apoptosis, and delays AML development. Ectopic expression of ALKBH5 partially mediates the function of USP9X in AML. Overall, this study uncovers deubiquitinase USP9X as a key for stabilizing ALKBH5 expression and reveals the important role of USP9X in AML, which provides a promising therapeutic strategy for AML treatment in the clinic.

Hepatitis E virus and Klebsiella pneumoniae co-infection detected by metagenomics next-generation sequencing in a patient with central nervous system and bloodstream Infection: a case report.

BACKGROUND: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide with major prevalence in the developing countries and can cause extrahepatic disease including the nervous system. Central nervous system infections caused by HEV are rare and caused by HEV together with other bacteria are even rarer. CASE PRESENTATION: A 68-year-old man was admitted to the hospital due to a headache lasting for 6 days and a fever for 3 days. Lab tests showed significantly raised indicators of inflammation, cloudy cerebrospinal fluid, and liver dysfunction. Hepatitis E virus and Klebsiella pneumoniae were identified in the blood and cerebrospinal fluid using metagenomic next-generation sequencing. The patient received meropenem injection to treat K. pneumoniae infection, isoglycoside magnesium oxalate injection and polyene phosphatidylcholine injection for liver protection. After ten days of treatment, the patient improved and was discharged from the hospital. CONCLUSION: Metagenomic next-generation sequencing, which can detect various types of microorganisms, is powerful for identifying complicated infections.

YBX1 is required for maintaining myeloid leukemia cell survival by regulating BCL2 stability in an m6A-dependent manner.

RNA-binding proteins (RBPs) are critical regulators of transcription and translation that are often dysregulated in cancer. Although RBPs are increasingly recognized as being important for normal hematopoiesis and for hematologic malignancies as oncogenes or tumor suppressors, RBPs that are essential for the maintenance and survival of leukemia remain elusive. Here we show that YBX1 is specifically required for maintaining myeloid leukemia cell survival in an N6-methyladenosine (m6A)-dependent manner. We found that expression of YBX1 is significantly upregulated in myeloid leukemia cells, and deletion of YBX1 dramatically induces apoptosis and promotes differentiation coupled with reduced proliferation and impaired leukemic capacity of primary human and mouse acute myeloid leukemia cells in vitro and in vivo. Loss of YBX1 has no obvious effect on normal hematopoiesis. Mechanistically, YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. Moreover, YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and BCL2 in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1. Thus, our findings have uncovered a selective and critical role of YBX1 in maintaining myeloid leukemia survival, which might provide a rationale for the therapeutic targeting of YBX1 in myeloid leukemia.

Pax transactivation domain-interacting protein is required for preserving hematopoietic stem cell quiescence via regulating lysosomal activity.

Hematopoietic stem cells (HSC) maintain lifetime whole blood hematopoiesis through self-renewal and differentiation. In order to sustain HSC stemness, most HSC reside in a quiescence state, which is affected by diverse cellular stress and intracellular signal transduction. How HSC accommodate those challenges to preserve lifetime capacity remains elusive. Here we show that Pax transactivation domain-interacting protein (PTIP) is required for preserving HSC quiescence via regulating lysosomal activity. Using a genetic knockout mouse model to specifically delete Ptip in HSC, we find that loss of Ptip promotes HSC exiting quiescence, and results in functional exhaustion of HSC. Mechanistically, Ptip loss increases lysosomal degradative activity of HSC. Restraining lysosomal activity restores the quiescence and repopulation potency of Ptip-/- HSC. Additionally, PTIP interacts with SMAD2/3 and mediates transforming growth factor-ß signaling-induced HSC quiescence. Overall, our work uncovers a key role of PTIP in sustaining HSC quiescence via regulating lysosomal activity.

Effect of two different laparoscopic techniques on post-operative wound complications in patients with benign gynaecological diseases: A meta-analysis.

Single-port laparoscopy (SPL) has existed for several years. This meta-analysis was conducted to evaluate the efficacy of SPL compared with conventional laparoscopy (CL) in the treatment of benign gynecologic adnexal lesions. The purpose of this meta-analysis is to evaluate the superiority of SPL versus CL in the treatment of post-operative wound pain. The study looked for English-language publications from PubMed, Embase, Cochrane Library and the Web of Science until June 2023. The main result was the visual analogue scale (VAS) after 2, 4, 6, 8, 12, 24 and 48 h after operation. The paper contains 10 related papers by means of e-search. Of these, 4 were randomized controlled trials (RCTs), while 6 were non-RCTs. The results indicated that SPL and CL were significantly different after 2, 24 and 48 h after operation. SPL had lower post-operative pain after 2 h compared with CL (MD, -0.6; 95% CI, -0.98, -0.21; p = 0.002). After the operation, SPL also had a lower incidence of post-operative pain after 24 h compared with CL (MD, -0.59; 95% CI, -1.12, -0.06; p = 0.03). And the difference in pain was at 48 h after the most significant (MD, -0.49; 95% CI, -0.75, -0.23; p = 0.0002). But after 6, 8 and 12 h after operation, there was no significant difference in the degree of pain. Thus, SPL operations may result in a lower degree of pain than CL in both the post-operative and far post-operative phase.

Serum NGAL Is Superior to Cystatin C in Predicting the Prognosis of Acute-on-Chronic Liver Failure.

INTRODUCTION AND AIM: Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). MATERIALS AND METHODS: This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. RESULTS: Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004-1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001-1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥ 217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. CONCLUSION: The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.

Case report: Imaging of adrenal adenomatoid tumors: reports of two cases and review of literature.

Adenomatoid tumors (ATs) are uncommon, benign tumors of mesothelial origin, most frequently found in the genital tracts of both sexes. Extragenital localization sites, such as adrenal glands, are extremely rare. Since patients with adrenal ATs have no obvious clinical symptoms, imaging examination has become important evidence for diagnosis. Although previous literature noted that the imaging findings of adrenal ATs were nonspecific, no relevant studies have confirmed this. We herein present two novel cases of adrenal ATs, confirmed by immunohistochemistry, and that were initially misdiagnosed as other, more common adrenal tumors based on clinical findings and preoperative imaging. Including our cases, we collected a total of 33 previously reported adrenal ATs and extracted all available imaging information from them, aiming to find some radiological characteristics of this rare tumor. Through the review, we identified some nonspecific imaging features of adrenal ATs; however, the final diagnosis still depends on pathology and immunohistochemistry results.

A Case report: Synovial sarcoma of the mediastinum in an 18-year-old teenager.

Synovial sarcomas (SSs) are a rare group of malignant tumors originating from pluripotential mesenchymal cells, which commonly occur as the primary tumor in the soft tissues near the articular surface, tendons, and articular synovium. Herein, we report a rare case of mediastinal SS in an 18-year-old teenager who initially presented with cough as the primary symptom. In this case, plain chest CT and contrast-enhanced CT clearly revealed the lesion presenting as a round-like and uneven density mass in the mediastinum with heterogeneous enhancement, which compressed the trachea and invaded the adjacent vessels. Based on the results of immunohistochemistry and fluorescence in situ hybridization (FISH), combined with the differential diagnosis with other types of tumors in the mediastinum on imaging, we were able to diagnose the tumor as an SS located in the mediastinum. Subsequent resection of the lesion coupled with chemotherapy and immunotherapy led to an improvement in the patient's symptoms.

Low Dose Iodinated Contrast Material and Radiation for Virtual Monochromatic Imaging in Craniocervical Dual-Layer Spectral Detector Computed Tomography Angiography: A Prospective and Randomized Study.

RATIONALE AND OBJECTIVES: To investigate the feasibility of virtual monochromatic imaging (VMI) of dual-layer spectral detector computed tomography (SDCT) to reduce iodinated contrast material (CM) and radiation dose in craniocervical computed tomography angiography (CTA). MATERIALS AND METHODS: A total of 280 consecutively selected patients performed craniocervical CTA with SDCT were prospectively selected and randomly divided into four groups (A, DoseRight index (DRI) 31, iopromide 370mgI/mL, volume 0.8 mL/kg; B, DRI 26, iopromide 370mgI/mL, volume 0.4 mL/kg; C, DRI 26, ioversol 320mgI/mL, volume 0.4 mL/kg; D, DRI 26, iohexol 300mgI/mL, volume 0.4 mL/kg). 50-70 kiloelectron volts (keV) VMIs in group B were reconstructed and compared to group A to select the optimal keV. Then, the optimal keV in groups B, C and D was reconstructed and compared. Objective image quality, including vascular attenuation, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), was evaluated. Subjective image quality was assessed using a 5-point Likert scale. In addition, the effective dose (ED), iodine load and iodine delivery rate (IDR) were compared between groups A and D. RESULTS: 55 keV VMI was the optimal VMI in group B. The objective and subjective image quality of 55 keV VMI in group B were equal to or better than those of the CI in group A. The SNR, CNR and subjective image quality in group D were similar to those in group B (P > 0.05). The ED, iodine load and IDR of group D were reduced by 44%, 59% and 19%, respectively, when compared to those of group A. CONCLUSION: Low dose iodinated CM and radiation for 55 keV VMI in craniocervical CTA using SDCT could still provide equivalent or better image quality than the conventional scanning protocol.

One-step Sintering Synthesis of Ni3Se2-Ni Electrode with Robust Interfacial Bonding for Ultra-stable Hydrogen Evolution Reaction.

Exploring efficient and robust self-supporting hydrogen evolution reaction (HER) electrodes using simple, accessible, and low-cost synthetic processes is crucial for the commercial application of water electrolysis at high current densities. Ni-based self-supporting electrodes are widely studied owing to their low cost and good catalytic performance. However, to date, the preparation of Ni-based electrodes requires multistep and complex preparation processes. In this study, a novel one-step in situ sintering method to synthesize mechanically stable and highly active Ni3Se2-Ni electrodes with well-controlled morphologies and structures is developed. Their excellent performance and durability can be attributed to the numerous highly active nano-Ni3Se2 catalysts embedded on the surface of the Ni skeleton, the excellent conductivity of the interconnected conductive network, and the strong interfacial bonding between Ni3Se2 and Ni. As a result, the Ni3Se2-Ni600 electrode can operate stably at 85 and 400 mA cm-2 for more than 800 and 300 h, respectively. Moreover, the Ni3Se2-Ni600 electrode displays outstanding stability for over 500 h in a commercial two-electrode system. This study provides a feasible one-step synthesis method for low-cost, high-efficiency metal selenide-metal self-supporting electrodes for water electrolysis.

Combinations of Clinical Factors, CT Signs, Radiomics for Differentiating High-density Areas After Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Clinically, hemorrhagic transformation (HT) after mechanical thrombectomy (MT) is a common complication. This study is aim to investigate the value of clinical factors, CT signs, and radiomics in the differential diagnosis of high-density areas (HDAs) in the brain after MT in patients with acute ischemic stroke with large vessel occlusion (AIS-LVO). MATERIALS AND METHODS: A total of 156 eligible patients with AIS-LVO in Center Ⅰ from December 2015 to June 2023 were retrospectively enrolled and randomly divided into training (n=109) and internal validation (n=47) sets at a ratio of 7:3. The data of 63 patients in Center Ⅱ were collected as an external validation set. According to the diagnostic criteria, the patients in the three datasets were divided into a HT group and a non-HT group. The clinical and imaging data from Centers Ⅰ and Ⅱ were used to construct a clinical factor and CT-sign model, a radiomic model and a combined model by logistic regression (LR). Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of each model in the three datasets. RESULTS: Clinical blood glucose (Glu) and the maximum cross-sectional area (Areamax) on CT were associated with the nature of the HDA according to multivariate LR analyses (P < 0.05). Among the three models, the combined model had the highest diagnostic efficiency, with area under the curve (AUC) values of 0.895, 0.882, and 0.820 in the three datasets, which were significantly greater than the AUC values of the radiomic model (0.887, 0.898, 0.798) and clinical factor and CT sign model (0.831, 0.744, 0.684). CONCLUSIONS: The combined model based on radiomics had the best performance, indicating that radiomic features can be used as imaging biomarkers to aid in the clinical judgment of the nature of HDA after MT. ABBREVIATIONS: HDA =high-density area; HT =hemorrhagic transformation; MT =mechanical thrombectomy; AIS-LVO =acute ischemic stroke with large vessel occlusion; LR =logistic regression; AUC =area under the curve; ICE =iodine contrast extravasation; DECT =dual energy CT; IOM =iodine overlay map; VNC =virtual noncontrast; Glu =glucose; LASSO =least absolute shrinkage and selection operator; ICC =intraclass correlation coefficient; ROC =receiver operating characteristic; DCA =decision curve analysis.

Dynamic transcriptomic and regulatory networks underpinning the transition from fetal primordial germ cells to spermatogonia in mice.

The transition from fetal primordial germ cells (PGCs) to spermatogonia (SPG) is critical for male germ cell development; however, the detailed transcriptomic dynamics and regulation underlying this transition remain poorly understood. Here by interrogating the comprehensive transcriptome atlas dataset of mouse male germ cells and gonadal cells development, we elucidated the regulatory networks underlying this transition. Our single-cell transcriptome analysis revealed that the transition from PGCs to SPG was characterized by global hypertranscription. A total of 315 highly active regulators were identified to be potentially involved in this transition, among which a non-transcription factor (TF) regulator TAGLN2 was validated to be essential for spermatogonial stem cells (SSCs) maintenance and differentiation. Metabolism profiling analysis also revealed dynamic changes in metabolism-related gene expression during PGC to SPG transition. Furthermore, we uncovered that intricate cell-cell communication exerted potential functions in the regulation of hypertranscription in germ cells by collaborating with stage-specific active regulators. Collectively, our work extends the understanding of molecular mechanisms underlying male germ cell development, offering insights into the recapitulation of germ cell generation in vitro.

Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance.

Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.

Critical Techniques for Overcoming the Diffusion Limitations in Heterogeneously Catalytic Depolymerization of Lignin.

Heterogeneously catalyzed depolymerization of lignin to value-added chemicals is increasingly attractive but highly challengeable. Particularly, the diffusion limitation of lignin macromolecule to the solid catalyst surface is a big barrier, which significantly decreases the yield of monomer while increasing char formation. Therefore, for the potential industrial utilization of lignin, new knowledge focused on the size of lignin particles is of great importance to offer guidance for promoting lignin depolymerization and suppressing condensation in the heterogeneously catalytic systems. In this Review, the size of lignin particles and macromolecules are summarized. Previous approaches for improving the mass diffusion including enhancing the solubility of lignin and exploitation of hierarchical and "solubilized" materials are also discussed. Based on these, a constructive perspective is proposed. Thus, this work provides a new insight on the rational design of heterogeneous catalytic techniques for efficient utilization of the aromatic polymer of lignin.

Application of Gradient-Dependent Optimal Interpolation in Fishery Analysis of Neon Flying Squid (Ommastrephes bartramii) in the Kuroshio-Oyashio Confluence Region.

A key issue in fishery forecasting is the collection of high-precision subsurface environmental data. A data assimilation method, named gradient-dependent optimal interpolation, was used to construct the near-real-time vertical temperature and salinity structure of a squid fishery ground based on Argo observations. The results were verified by truth-finding comparisons and applied to analyze the relationship between neon flying squid and the subsurface environment in the Kuroshio-Oyashio Confluence Region. The temperature and salinity differences between the constructed results and survey data were less than ±0.5 °C and ±0.02, respectively. Most of the relative analysis errors were less than the observational errors. Statistical analysis revealed that the most suitable temperature for squid was 18-24 °C at the near-surface (<5 m), although the squid can endure a temperature range from 11 to 12 °C at a depth of 300 m. There was an obvious thermocline in the fishery ground, with a thermocline depth of 65 m and a mean strength of approximately 0.10 °C/m. The regressive relationship between vertical temperature (thermocline parameters) and squid catch per unit effort (CPUE) followed the exponential (Gaussian) function. The most suitable salinity was 33.0-34.2 at depths shallower than 300 m.

Pyogenic liver abscess caused by extended-spectrum ß-lactamase-producing hypervirulent Klebsiella pneumoniae diagnosed by third-generation sequencing: a case report and literature review.

We report a case of a woman with diabetes mellitus and choledocholithiasis who had a low fever with chills and severe weakness for 7 days. The patient's abdominal tenderness was positive. Computed tomography and magnetic resonance imaging showed a giant abscess in the liver. The production of extended-spectrum ß-lactamases by hypervirulent Klebsiella pneumoniae was found in the purulent fluid of the liver by nanopore-based metagenomic third-generation sequencing combined with an antibiotic susceptibility test. The patient recovered after intravenous antibiotic therapy and percutaneous drainage. Patients with a history of diabetes mellitus and choledocholithiasis should be aware of the possibility of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae. To rapidly control the development of this disease, nanopore-based metagenomic third-generation sequencing plays an important role not only in rapidly identifying pathogens, but also in guiding the use of antibiotics.

A Rational Design of a CoS2-CoSe2 Heterostructure for the Catalytic Conversion of Polysulfides in Lithium-Sulfur Batteries.

Lithium-sulfur batteries are anticipated to be the next generation of energy storage devices because of their high theoretical specific capacity. However, the polysulfide shuttle effect of lithium-sulfur batteries restricts their commercial application. The fundamental reason for this is the sluggish reaction kinetics between polysulfide and lithium sulfide, which causes soluble polysulfide to dissolve into the electrolyte, leading to a shuttle effect and a difficult conversion reaction. Catalytic conversion is considered to be a promising strategy to alleviate the shuttle effect. In this paper, a CoS2-CoSe2 heterostructure with high conductivity and catalytic performance was prepared by in situ sulfurization of CoSe2 nanoribbon. By optimizing the coordination environment and electronic structure of Co, a highly efficient CoS2-CoSe2 catalyst was obtained, to promote the conversion of lithium polysulfides to lithium sulfide. By using the modified separator with CoS2-CoSe2 and graphene, the battery exhibited excellent rate and cycle performance. The capacity remained at 721 mAh g-1 after 350 cycles, at a current density of 0.5 C. This work provides an effective strategy to enhance the catalytic performance of two-dimensional transition-metal selenides by heterostructure engineering.

The image quality and diagnostic performance of CT perfusion-derived CT angiography versus that of conventional CT angiography.

Background: The combination of computed tomography angiography (CTA) and computed tomography perfusion (CTP) evaluation of cerebral perfusion status and vascular conditions can improve the diagnostic accuracy of infarction, ischemia, and vascular occlusion in stroke patients, as well as a comprehensive assessment of cerebral edema, collateral circulation, and blood perfusion in the lesion area. However, the consequent radiation safety and contrast agent nephropathy have aroused increasing concern. The purpose of this study was to assess the image quality and diagnostic accuracy of CTA images derived from CTP data, and to explore the feasibility of replacing conventional CTA. Methods: A total of 31 consecutive patients with suspected acute ischemic stroke were retrospectively analyzed. All patients underwent head and neck CTA and brain CTP examinations. All the CTP images were transmitted to the ShuKun artificial intelligence system, which reconstructs CTA derived from CTP (CTA-DF-CTP). The images were divided into 2 groups, including CTA-DF-CTP (Group A) and conventional CTA (Group B). The CT attenuation values, subjective image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, CT volume dose index (CTDIvol), dose length product (DLP), and effective radiation dose (ED) were compared between the 2 groups. Moreover, the consistency of vascular stenosis and stenosis degree between the 2 groups were measured and evaluated. Results: There were no significant differences in image noise, SNR, or CNR between Groups A and B (P>0.05). The CT attenuation values of the arteries were higher in Group A than in B [internal carotid artery (ICA) =548±112 vs. 454±85 Hounsfield units (HU), middle cerebral artery (MCA) =453±118 vs. 388±70 HU, and basilar artery (BA) =431±99 vs. 360±83 HU] (P<0.01). The image quality of the 2 groups met the requirement of clinical diagnosis (4.97±0.18 vs. 4.94±0.25). No significant difference was found in subjective evaluation (P>0.05). In Group A compared with Group B, the following reductions were observed: CTDIvol (10.7%; 100.8 vs. 112.9 mGy), DLP (23.0%; 1,613±0 vs. 2,093±88 mGy·cm), and ED (23.0%; 5.00±0.00 vs. 6.49±0.27 mSv). Conclusions: CTA-DF-CTP data provide diagnostic accuracy and image quality similar to those of conventional CTA of head and neck CTA.

Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance.

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.