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.

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.

One-step Sintering Synthesis of Ni3 Se2 -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 Ni3 Se2 -Ni electrodes with well-controlled morphologies and structures is developed. Their excellent performance and durability can be attributed to the numerous highly active nano-Ni3 Se2 catalysts embedded on the surface of the Ni skeleton, the excellent conductivity of the interconnected conductive network, and the strong interfacial bonding between Ni3 Se2 and Ni. As a result, the Ni3 Se2 -Ni600 electrode can operate stably at 85 and 400 mA cm-2 for more than 800 and 300 h, respectively. Moreover, the Ni3 Se2 -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.

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.

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.

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.

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.

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.

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.

Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.

Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by simultaneously investigating the chromatin accessibility, DNA methylome and transcriptome landscapes using the modified single-cell chromatin overall omic-scale landscape sequencing approach, we revealed that the transcriptional changes throughout human spermatogenesis were correlated with chromatin accessibility changes. In particular, we identified a set of transcription factors and cis elements with potential functions. A round of DNA demethylation was uncovered upon meiosis initiation in human spermatogenesis, which was associated with male meiotic recombination and conserved between human and mouse. Aberrant DNA hypermethylation could be detected in leptotene spermatocytes of certain nonobstructive azoospermia patients. Functionally, the intervention of DNA demethylation affected male meiotic recombination and fertility. Our work provides multi-omics landscapes of human spermatogenesis at single-cell resolution and offers insights into the association between DNA demethylation and male meiotic recombination.

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.

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.

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.

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.

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.

Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection.

Round spermatid injection (ROSI) technique holds great promise for clinical treatment of a proportion of infertile men. However, the compromised developmental potential of ROSI embryos largely limits the clinical application, and the mechanisms are not fully understood. Here, we describe the transcriptome, chromatin accessibility, and DNA methylation landscapes of mouse ROSI embryos derived from early-stage round spermatids using a single-cell multiomics sequencing approach. By interrogating these data, we identify the reprogramming defects in ROSI embryos at the pronuclear stages, which are mainly associated with the misexpression of a cohort of minor zygotic genome activation genes. We screen a small compound, A366, that can significantly increase the developmental potential of ROSI embryos, in which A366 can partially overcome the reprogramming defects by amending the epigenetic and transcriptomic states. Collectively, our study uncovers the reprogramming defects in ROSI embryos for understanding the mechanisms underlying compromised developmental potential and offers an avenue for ROSI technique optimization.

PTIP governs NAD+ metabolism by regulating CD38 expression to drive macrophage inflammation.

NAD+ metabolism is involved in many biological processes. However, the underlying mechanism of how NAD+ metabolism is regulated remains elusive. Here, we find that PTIP governs NAD+ metabolism in macrophages by regulating CD38 expression and is required for macrophage inflammation. Through integrating histone modifications with NAD+ metabolic gene expression profiling, we identify PTIP as a key factor in regulating CD38 expression, the primary NAD+-consuming enzyme in macrophages. Interestingly, we find that PTIP deletion impairs the proinflammatory response of primary murine and human macrophages, promotes their metabolic switch from glycolysis to oxidative phosphorylation, and alters NAD+ metabolism via downregulating CD38 expression. Mechanistically, an intronic enhancer of CD38 is identified. PTIP regulates CD38 expression by cooperating with acetyltransferase p300 in establishing the CD38 active enhancer with enriched H3K27ac. Overall, our findings reveal a critical role for PTIP in fine-tuning the inflammatory responses of macrophages via regulating NAD+ metabolism.

Case report: Primary mediastinal Ewing's sarcoma presenting with chest tightness.

Ewing's sarcoma is a part of a rare group of malignant neoplasms, whose pathological morphological features are small round cells. Extraskeletal Ewing's sarcoma is a more uncommon primary tumor. Herein, we report the case of a 66-year-old man who complained of chest tightness. Subsequent chest CT scans revealed an irregular and uneven density mass on the right side of the anterior mediastinum with invasion of the superior vena cava, pericardium and right lung. The patient's clinical symptoms were improved after performing excision of the mediastinal lesions under cardiopulmonary bypass. Based on histological and immunohistochemical findings, the tumor was diagnosed as extraskeletal Ewing's sarcoma.

Differential m6A RNA landscapes across hematopoiesis reveal a role for IGF2BP2 in preserving hematopoietic stem cell function.

N6-methyladenosine (m6A) on mRNA plays critical roles in various cellular processes. However, the landscape and dynamics of m6A modification in hematopoietic system remain unknown. Here, we delineate a comprehensive m6A landscape across hematopoietic hierarchy and uncover that IGF2BP2 is required for preserving the function of hematopoietic stem cells (HSCs). Our data reveal a cell-type-specific m6A landscape in hematopoiesis. m6A modifications arise mostly in the early stage of hematopoiesis and prefer to play distinct roles for determining mRNA fates in HSCs and committed progenitors. Mechanistically, increased m6A-IGF2BP2 expression controls transcriptional state and maintenance of HSCs. IGF2BP2 deficiency induces quiescence loss and impairs HSC function. Moreover, IGF2BP2 loss increases mitochondrial activity of HSCs by accelerating Bmi1 mRNA decay, leading to de-repression of mitochondria-related genes. Collectively, our results present a fascinating portrait of m6A modification of hematopoietic hierarchy and reveal a key role of IGF2BP2 in maintaining HSC function by restraining mitochondrial activity.

Cell-fate transition and determination analysis of mouse male germ cells throughout development.

Mammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells' identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.