Glycine-Ti3C2Tx Hybrid Material Improves the Electrochemical Corrosion Resistance of a Water-Borne Epoxy Coating.

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

Transcriptomic analysis reveals the inhibitory effect of beta-sitosterol on proliferation of bovine preadipocytes.

Fat deposition affects beef quantity and quality via preadipocyte proliferation. Beta-sitosterol, a natural small molecular compound, has various functions, such as anti-inflammation, antibacterial, and anticancer properties. The mechanism of action of Beta-sitosterol on bovine preadipocytes remains unclear. This study, based on RNA-seq, reveals the impact of Beta -sitosterol on the proliferation of bovine preadipocytes. Compared to the control group, Beta-sitosterol demonstrated a more pronounced inhibitory effect on cell proliferation after 48 hours of treatment than after 24 hours, as evidenced by the results of EdU staining and flow cytometry. RNA-seq and Western Blot analyses further substantiated these findings. Our results suggest that the impact of Beta-sitosterol on the proliferation of bovine preadipocytes is not significant after a 24-hour treatment. It is only after extending the treatment time to 48 hours that Beta-sitosterol may induce cell cycle arrest at the G2/M phase by suppressing the expression of CCNB1, thereby inhibiting the proliferation of bovine preadipocytes.

Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma.

As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment. The present investigation endeavors to explore the potential of M1 macrophage-related genes (MRGs) as biomarkers for assessing risk in individuals with osteosarcoma. RNA-sequence data and clinical data were derived from TCGA and GEO databases. The CIBERSORT method was utilized to discern subtypes of tumor-infiltrating immune cells. Identification of MRGs was achieved through Pearson correlation analysis. A prognostic risk model for MRGs was developed using Cox and LASSO regression analyses. A tripartite gene signature comprising CD37, GABRD, and ARHGAP25 was an independent prognostic indicator and was employed to develop a risk score model. The internal and external validation cohort confirmed the results. The area under the ROC curve (AUC) was determined for survival periods of 1 year, three years, and five years, yielding values of 0.746, 0.839, and 0.850, respectively. The C-index of the risk score was found to be superior to clinicopathological factors. GO/KEGG enrichment showed that the differences between high- and low-risk groups were predominantly associated with immune response pathways. Immune-related analysis related to proportions of immune cells, immune function, and expression levels of immune checkpoint genes all showed differences between the high- and low-risk groups. The qRT-PCR and Western blotting results indicate that CD37 expression was markedly higher in MG63 and U2OS cell lines when compared to normal osteoblast hFOB1.19. In U2OS cell line, GABRD expression levels were significantly upregulated. ARHGAP25 expression levels were elevated in both 143B and U2OS cell lines. In summary, utilizing a macrophage genes signature demonstrates efficacy in predicting both the prognosis and therapy response of OS. Additionally, immune analysis confirms a correlation between the risk score and the tumor microenvironment. Our findings, therefore, provide a cogent account for the disparate prognoses observed among patients and furnish a justification for further inquiry into biomarkers and anti-tumor treatment strategies.

Proximal femoral nail anti-rotation vs dynamic hip screws decrease the incidence of surgical site infections in patients with intertrochanteric fractures: A meta-analysis.

In this study, a meta-analysis was conducted to comprehensively analyse the effectiveness of using proximal femoral nail anti-rotation (PFNA) and dynamic hip screws (DHS) to treat intertrochanteric fractures on postoperative surgical site infections (SSI). PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from their inception until December 2022 to identify studies that compared PFNA and DHS in the treatment of intertrochanteric fractures. Two investigators independently screened the retrieved studies to assess their quality and verify their eligibility for inclusion. Meta-analyses were performed with RevMan 5.4 software. Thirty studies, including 3158 patients, met the inclusion criteria. These studies included 1574 patients treated with PFNA, and 1584 were treated with DHS. The findings of the meta-analysis revealed a significant reduction in the incidence of SSI in patients treated with PFNA compared with those treated with DHS (2.64% vs 6.76%, odds ratio [OR]: 0.40, 95% confidence intervals [CIs]: 0.28-0.57, P < .001), superficial SSI (2.58% vs 5.01%, OR: 0.53, 95% CIs: 0.33-0.85, P = .008) and deep SSI (1.26% vs 3.43%, OR: 0.41, 95% CIs: 0.19-0.92, P = .03). PFNA was more effective than DHS in reducing the incidence of SSI. Even so, significant variations in sample sizes among the included studies meant that the methodology for some studies had qualitative deficiencies. Therefore, additional studies with large sample sizes are needed to validate these results.

Oxr1a prevents the premature ovarian failure by regulating oxidative stress and mitochondrial function in zebrafish.

Premature ovarian failure (POF) is characterized as the ovarian dysfunction and defective oocyte development. In POF patients, ROS level is reported to be significantly higher than normal individuals. However, the involvement of oxidative stress in POF and the regulatory mechanisms underlying the antioxidative process in oocyte development remain largely unknown. Here, we discover that oxidation resistance 1a (Oxr1a), the ortholog of mammalian Oxr1, protects the oocytes of female zebrafish against oxidative stress and thus represses the POF phenotype. Oxr1a was widely expressed in oocytes at different developmental stages, of which the mRNA expression levels were significantly upregulated upon follicle activation and oocyte maturation. Oxr1a knockout exacerbated the POF phenotype, as evidenced by the decreased number and quality of oocytes. Moreover, the oocytes of oxr1a knockout zebrafish exhibited excessive ROS, increased mitochondrial DNA damage, reduced mitochondria, and abnormal morphology. Mechanistically, instead of decomposing ROS directly, Oxr1a participated in the process of oxidative stress through regulating the mRNA expression levels of the key antioxidant enzymes Cat and Sod1. Moreover, treatment with antioxidant N-Acetyl-l-cysteine attenuated the mitochondrial oxidative damage and improved the fertility of mutant females, indicating that Oxr1a may mediates the Sod1/Cat pathway to metabolize the intracellular ROS and avoid the mitochondrial oxidative damage, thus ensuring the normal development and maturation of oocytes. Taken together, these findings are useful for the elucidation of molecular mechanisms underlying the oxidative damage in oocytes and beneficial to the clinical therapeutics of POF.

Integrin αVß3 Signaling in the Progression of Osteoarthritis Induced by Excessive Mechanical Stress.

Osteoarthritis (OA) is believed to be linked with cartilage degeneration, subchondral bone sclerosis, and synovial inflammation that lead to joint failure, and yet treatment that can effectively reverse the pathological process of the disease still not exists. Recent evidence suggests excessive mechanical stress (eMS) as an essential role in the pathogenesis of OA. Increased levels of integrin αVß3 have been detected in osteoarthritic cartilage and were previously implicated in OA pathogenesis. However, the role of integrin αVß3 in the process of eMS-induced OA remains unclear. Here, histologic and proteomic analyses of osteoarthritic cartilage in a rat destabilization of the medial meniscus model demonstrated elevated expression of integrin αVß3 as well as more serious cartilage degeneration in the medial weight-bearing area. Furthermore, results of in vitro study demonstrated that eMS led to a significant increase of integrin αVß3 expression and phosphorylation of downstream signaling molecules such as FAK and ERK, as well as upregulated expressions of inflammatory and degradative mediators. In addition, we found that inhibition of integrin αVß3 could alleviate chondrocyte inflammation triggered by eMS both in vivo and in vitro. Our findings suggest a central role for upregulation of integrin αVß3 signaling in OA pathogenesis and demonstrate that activation of integrin αVß3 signaling in cartilage contributes to inflammation and joint destruction in eMS-induced OA. Taken together, our data presented here provide a possibility for targeting integrin αVß3 signaling pathway as a disease-modifying therapy.

One-Pot Synthesis of Pyreno[2,1-b]furan Molecules with Two-Photon Absorption Properties.

The development of large π-conjugated polycyclic heteroaromatic materials is of immense interest, both in the academic as well as the industrial community. Herein, we present the efficient one-pot synthesis of novel pyreno[2,1-b]furan molecules from a newly designed intermediate, which display intense green emission (505-516 nm) in solution and a large red shift emission (625-640 nm) in the solid state, because of strong π-π stacking. More interestingly, the compounds exhibit novel two-photon absorption (TPA) properties, and the TPA cross-section (δ) value was increased to 533 GM by regulating the electronic effects of the substituents of the pyreno[2,1-b]furan molecules. This study not only offers a facile strategy for constructing new pyrene-fused luminescence materials with two-photon absorption properties but also provides a new chemical intermediate that opens up a new pathway to advanced materials.

Intermolecular Hydrogen-Bond-Assisted Solid-State Dual-Emission Molecules with Mechanical Force-Induced Enhanced Emission.

Hydrogen bonds not only play a crucial role in the life sciences but also endow molecules with fantastic physical and chemical properties, which help in the realization of their high-tech applications. This work presents an efficient strategy for achieving highly efficient solid-state dual-emission blue emitters with mechanical force-induced enhanced emission properties via intermolecular hydrogen bonds via novel pyrene-based intermediates, namely, 1,3,6,8-tetrabromo-2,7-dihydroxypyrene (1) and 1,3,6,8-tetrabromo-2-hydroxypyrene (2), prepared via hydroxylation and bromination of pyrene in high yields. Moreover, further use of a classical Pd-catalyzed coupling reaction affords new pyrene-based luminescent materials 3-5, which display high thermal stability (in range of 336-447 °C), blue emission (<463 nm), and high quantum yields in solution. Interestingly, with the monosubstituted hydroxyl (OH) or methoxy (OMe) group located at position 2 of pyrene, compounds 4a and 5 display exciting dual emission with mechanical force-induced enhanced emission properties, due to the presence of several hydrogen-bond interactions. Moreover, this series of compounds exhibits numerous advantages, for example, deeper blue emission with a narrower full width at half-maximum, a stronger steric effect, and higher hydrophilicity. Thus, these novel bromopyrene intermediates and related pyrene-based luminescent materials will pave the way for further exploration of novel organic solid-state luminescent materials for potential application in organic electronics, bioimaging, chemosensors, etc.

Large-Scale Domain Engineering in Two-Dimensional Ferroelectric CuInP2S6 via Giant Flexoelectric Effect.

Room-temperature ferroelectricity in two-dimensional (2D) materials is a potential for developing atomic-scale functional devices. However, as a key step for the technology implementations of 2D ferroelectrics in electronics, the controllable generation of uniform domains remains challenging at the current stage because domain engineering through an external electric field at the 2D limit inevitably leads to large leakage currents and material breakdown. Here, we demonstrate a voltage-free method, the flexoelectric effect, to artificially generate large-scale stripe domains in 2D ferroelectric CuInP2S6 with single domain lateral size at the scale of several hundred microns. With giant strain gradients (∼106 m-1), we mechanically switch the out-of-plane polarization in ultrathin CuInP2S6. The flexoelectric control of polarization is understood with a distorted Landau-Ginzburg-Devonshire double well model. Through substrate strain engineering, the stripe domain density is controllable. Our results highlight the potential of developing van der Waals ferroelectrics-based flexible electronics.

Room-Temperature Ferroelectricity in 1T

van der Waals materials possess an innate layer degree of freedom and thus are excellent candidates for exploring emergent two-dimensional ferroelectricity induced by interlayer translation. However, despite being theoretically predicted, experimental realization of this type of ferroelectricity is scarce at the current stage. Here, we demonstrate robust sliding ferroelectricity in semiconducting 1T^{'}-ReS_{2} multilayers via a combined study of theory and experiment. Room-temperature vertical ferroelectricity is observed in two-dimensional 1T^{'}-ReS_{2} with layer number N≥2. The electric polarization stems from the uncompensated charge transfer between layers and can be switched by interlayer sliding. For bilayer 1T^{'}-ReS_{2}, the ferroelectric transition temperature is estimated to be ∼405 K from the second harmonic generation measurements. Our results highlight the importance of interlayer engineering in the realization of atomic-scale ferroelectricity.

Nitrogen addition alleviated sexual differences in responses to cadmium toxicity by regulating the antioxidant system and root characteristics, and inhibiting Cd translocation in mulberry seedlings.

Cadmium (Cd) toxicity and nitrogen (N) deposition are two major environmental stresses which can affect plant growth. It's less clear that how the combined Cd accumulation and N deposition affect the male and female plants of dioecious species. The aim of the present study was to detect sex-specific responses to Cd stress and simulated N deposition in one-year-old male, female and hermaphrodite seedlings of Morus alba. Changes in morphology, physiology, root architecture and biomass of the three sex types of mulberry seedlings were determined. The results showed that Cd toxicity caused limited growth, impaired photosynthetic apparatus and decreased gas exchange rates with significant sex-specific differences. Mulberry was found to deploy detoxification mechanisms to avoid or tolerate toxic Cd effects through the activation of the antioxidant system, increasing proline and non-protein thiol contents, translocating Cd into different plant parts and decreasing biomass. Females displayed a low tolerance to high Cd and were more sensitive to Cd stress. Simulated N deposition alleviated the negative effects of Cd on leaves and decreased sex-specific differences in the three kinds of mulberry seedlings, but N fertilizer did not affect the total biomass. The N-stimulated increasing in proline and non-protein thiol contents might play a crucial role in resisting the damage caused by Cd stress, and the three kinds of mulberry seedlings had slightly different ways of improving Cd tolerance by N deposition. Sexual differences in Cd accumulation are correlated with root architecture. This study provides evidence for the utilization of mulberry to treat Cd-contaminated soils under N deposition.

Enhanced bulk photovoltaic effect in two-dimensional ferroelectric CuInP2S6.

The photocurrent generation in photovoltaics relies essentially on the interface of p-n junction or Schottky barrier with the photoelectric efficiency constrained by the Shockley-Queisser limit. The recent progress has shown a promising route to surpass this limit via the bulk photovoltaic effect for crystals without inversion symmetry. Here we report the bulk photovoltaic effect in two-dimensional ferroelectric CuInP2S6 with enhanced photocurrent density by two orders of magnitude higher than conventional bulk ferroelectric perovskite oxides. The bulk photovoltaic effect is inherently associated to the room-temperature polar ordering in two-dimensional CuInP2S6. We also demonstrate a crossover from two-dimensional to three-dimensional bulk photovoltaic effect with the observation of a dramatic decrease in photocurrent density when the thickness of the two-dimensional material exceeds the free path length at around 40 nm. This work spotlights the potential application of ultrathin two-dimensional ferroelectric materials for the third-generation photovoltaic cells.

Farnesoid X Receptor Is Required for the Redifferentiation of Bipotential Progenitor Cells During Biliary-Mediated Zebrafish Liver Regeneration.

BACKGROUND AND AIMS: Liver regeneration after extreme hepatocyte loss occurs through transdifferentiation of biliary epithelial cells (BECs), which includes dedifferentiation of BECs into bipotential progenitor cells (BPPCs) and subsequent redifferentiation into nascent hepatocytes and BECs. Although multiple molecules and signaling pathways have been implicated to play roles in the BEC-mediated liver regeneration, mechanisms underlying the dedifferentiation-redifferentiation transition and the early phase of BPPC redifferentiation that is pivotal for both hepatocyte and BEC directions remain largely unknown. APPROACH AND RESULTS: The zebrafish extreme liver damage model, genetic mutation, pharmacological inhibition, transgenic lines, whole-mount and fluorescent in situ hybridizations and antibody staining, single-cell RNA sequencing, quantitative real-time PCR, and heat shock-inducible overexpression were used to investigate roles and mechanisms of farnesoid X receptor (FXR; encoded by nuclear receptor subfamily 1, group H, member 4 [nr1h4]) in regulating BPPC redifferentiation. The nr1h4 expression was significantly up-regulated in response to extreme liver injury. Genetic mutation or pharmacological inhibition of FXR was ineffective to BEC-to-BPPC dedifferentiation but blocked the redifferentiation of BPPCs to both hepatocytes and BECs, leading to accumulation of undifferentiated or less-differentiated BPPCs. Mechanistically, induced overexpression of extracellular signal-related kinase (ERK) 1 (encoded by mitogen-activated protein kinase 3) rescued the defective BPPC-to-hepatocyte redifferentiation in the nr1h4 mutant, and ERK1 itself was necessary for the BPPC-to-hepatocyte redifferentiation. The Notch activities in the regenerating liver of nr1h4 mutant attenuated, and induced Notch activation rescued the defective BPPC-to-BEC redifferentiation in the nr1h4 mutant. CONCLUSIONS: FXR regulates BPPC-to-hepatocyte and BPPC-to-BEC redifferentiations through ERK1 and Notch, respectively. Given recent applications of FXR agonists in the clinical trials for liver diseases, this study proposes potential underpinning mechanisms by characterizing roles of FXR in the stimulation of dedifferentiation-redifferentiation transition and BPPC redifferentiation.

Nonvolatile Electric Control of Exciton Complexes in Monolayer MoSe2 with Two-Dimensional Ferroelectric CuInP2S6.

Monolayer transition-metal dichalcogenides (TMDs) have provided a platform to investigate the excitonic states at the two-dimensional (2D) limit. The inherent properties of excitons in TMDs, such as the photoluminescence quantum yield, the charge states, and even the binding energy, can be effectively controlled via electrostatic gating, selective carrier doping, or substrate dielectric engineering. Here, aiming for the nonvolatile electrical tunability of excitonic states and thereby the optical property of TMDs, we demonstrate a 2D ferroelectric heterostructure with monolayer MoSe2 and ultrathin CuInP2S6 (CIPS). In the heterostructure, the electric polarization of CIPS results in continuous, global, and large electronic modulation in monolayer MoSe2. With the saturated ferroelectric polarization of CIPS, electron-doped or hole-doped MoSe2 is realized in a single device. The carrier density tunability in the heterostructure is as high as 5 × 1012 cm-2. The nonvolatile behavior of these devices up to 3 months is also characterized. Our results provide a new and practical strategy for low-power consumption and agelong tunable optoelectronic devices.

An Air-Stable Organic Radical from a Controllable Photoinduced Domino Reaction of a Hexa-aryl Substituted Anthracene.

Air-stable organic radicals and radical ions have attracted great attention for their far-reaching application ranging from bioimaging to organic electronics. However, because of the highly reactive nature of organic radicals, the design and synthesis of air-stable organic radicals still remains a challenge. Herein, an air-stable organic radical from a controllable photoinduced domino reaction of a hexa-aryl substituted anthracene is described. The domino reaction involves a photoinduced [4 + 2] cycloaddition reaction, rearrangement, photolysis, and an elimination reaction; 1H/13C NMR spectroscopy, high resolution mass spectrometry, single-crystal X-ray diffraction, and EPR spectroscopy were exploited for characterization. Furthermore, a photoinduced domino reaction mechanism is proposed according to the experimental and theoretical studies. In addition, the effects of employing push and pull electronic groups on the controllable photoinduced domino reaction were investigated. This article not only offers a new blue emitter and novel air-stable organic radical compound for potential application in organic semiconductor applications, but also provides a perspective for understanding the fundamentals of the reaction mechanism on going from anthracene to semiquinone in such anthracene systems.

Bright and Near-Unity Polarized Light Emission Enabled by Highly Luminescent Cu2I2-Dimer Cluster-Based Hybrid Materials.

As one fundamental property of light, polarization has a huge impact in quantum optics and optoelectronics through light-matter interactions. However, the bright and near-unity polarized light emissions in the visible range by solid crystalline materials are scantly realized. Here, we report well-defined quasi two-dimensional (2D) hybrid crystals based on the linear alignment of Cu2I2-dimer/bidentate ligand hybrid clusters for achieving bright and near-unity linearly polarized light emissions. Using first-principle calculations, we demonstrate that the superaligned transition dipole moments are the key for the observed excellent polarized light emissions. To further enhance the photoluminescence (PL) polarization degree, we fabricate Cu2I2-dimer-based hybrid nanobelts, which display high PL quantum yield (up to 64%) and ultrahigh PL polarization degree (∼0.99). Our reported copper iodine cluster-based luminescent hybrid materials for bright and highly polarized light emissions will have great potential for future quantum optics applications.

Effect of layer and stacking sequence in simultaneously grown 2H and 3R WS2 atomic layers.

In two-dimensional layered materials, layer number and stacking order have strong effects on the optical and electronic properties. Tungsten disulfide (WS2) crystal, as one important member among transition metal dichalcogenides, has been usually prepared in a layered 2H prototype structure with space group P63/mmc ([Formula: see text]) in spite of many other expected ones such as 3R. Here, we report simultaneous growth of 2H and 3R stacked multilayer (ML) WS2 crystals in large scale by chemical vapor deposition and effects of layer number and stacking order on optical and electronic properties. As revealed in Raman and photoluminescence (PL) measurements, with an increase in layer number, 2H and 3R stacked ML WS2 crystals show similar variation of PL and Raman peaks in position and intensity. Compared to 2H stacked ML WS2, however, 3R stacked one always exhibits the larger red (blue) shift of Raman [Formula: see text] (A1g) peak and the appearance of PL A, B and I peaks at lower energies. Thereby, PL and Raman features depend on not only layer number but also stacking order. In addition, circularly polarized luminescence from two prototype WS2 crystals under circularly polarized excitation has also been investigated, showing obvious spin or valley polarization of these CVD-grown multilayer WS2 crystals.

Germline Stem Cells Drive Ovary Regeneration in Zebrafish.

Germline stem cells (GSCs) sustain gametogenesis during the organismal life cycle. Although evidence suggests that GSCs are consistently present in the zebrafish ovary and support oogenesis, whether GSCs are involved in zebrafish ovary regeneration is poorly understood. Here, we found that nanos2, a conserved vertebrate GSC marker, is required for maintaining GSCs in zebrafish. We applied genetic ablation and tissue resection techniques to delineate the function of GSCs in zebrafish ovary regeneration. After GSC ablation, ovaries fail to regenerate and are converted to sterile testes. Amputated ovarian tissues completely regenerate as a result of the proliferation of residual GSCs, but nanos2 mutant ovaries fail to regenerate after amputation due to a lack of GSCs. The repression of Wnt signaling leads to reduced numbers of GSCs and delayed ovary regeneration. Our results provide insight into the key role of GSCs in driving ovary regeneration.

Room-temperature ferroelectricity and a switchable diode effect in two-dimensional α-In2Se3 thin layers.

Nanoscale room-temperature ferroelectricity is ideal for developing advanced non-volatile high-density memories. However, reaching the thin film limit in conventional ferroelectrics is a long-standing challenge due to the presence of the critical thickness effect. van der Waals materials, thanks to their stable layered structure, saturated interfacial bonding and weak interlayer couplings, are promising for exploring ultra-thin two-dimensional (2D) ferroelectrics and device applications. Here, we demonstrate a switchable room-temperature ferroelectric diode built upon a 2D ferroelectric α-In2Se3 layer as thin as 5 nm in the form of a graphene/α-In2Se3 heterojunction. The intrinsic out-of-plane ferroelectricity of the α-In2Se3 thin layers is evidenced by the observation of reversible spontaneous electric polarization with a relatively low coercive electric field of ∼2 × 105 V cm-1 and a typical ferroelectric domain size of around tens µm2. Owing to the out-of-plane ferroelectricity of the α-In2Se3 layer, the Schottky barrier at the graphene/α-In2Se3 interface can be effectively tuned by switching the electric polarization with an applied voltage, leading to a pronounced switchable double diode effect with an on/off ratio of ∼105. Our results offer a new way for developing novel nanoelectronic devices based on 2D ferroelectrics.

Ribosome biogenesis protein Urb2 regulates hematopoietic stem cells development via P53 pathway in zebrafish.

Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease the population of HSCs in CHT and early T cells in thymus. Further analysis shows that compromised cell proliferation and superfluous apoptosis are observed in the CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42 mutant. These data demonstrate that urb2 is essential for HSCs development through the regulation of P53 pathway.