Polyhydroxy structure orchestrates the intrinsic antibacterial property of acrylamide hydrogel as a versatile wound-healing dressing.

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

A novel sponge composite of chitosan-sodium tripolyphosphate-melamine for anionic dye Orange II removal.

Since the potential carcinogenic, toxic and non-degradable dyes trigger serious environmental contamination by improper treatment, developing novel adsorbents remains a major challenge. A novel high efficiency and biopolymer-based environmental-friendly adsorbent, chitosan­sodium tripolyphosphate-melamine sponge (CTS-STPP-MS) composite, was prepared for Orange II removing with chitosan as raw material, sodium tripolyphosphate as cross-linking agent. The composite was carefully characterized by SEM, EDS, FT-IR and XPS. The influence of crosslinking conditions, dosage, pH, initial concentration, contacting time and temperature on adsorption were tested through batch adsorption experiments. CTS-STPP-MS adsorption process was exothermic, spontaneous and agreed with Sips isotherm model accompanying the maximum adsorption capacity as 948 mg∙g-1 (pH = 3). Notably, the adsorption performance was outstanding for high concentration solutions, with a removal rate of 97 % in up to 2000 mg∙L-1 OII solution (100 mg sorbent dosage, 50 mL OII solution, pH = 3, 289.15 K). In addition, the adsorption efficiency yet remained 97.85 % after 5 repeated adsorption-desorption cycles. The driving force of adsorption was attributed to electrostatic attraction and hydrogen bonds which was proved by adsorption results coupled with XPS. Owing to the excellent properties of high-effective, environmental-friendly, easy to separate and regenerable, CTS-STPP-MS composite turned out to be a promising adsorbent in contamination treatment.

Floatable Cu2(OH)PO4/rGO Aerogel for Full Spectrum Driven Photocatalytic Degradation of Organic Pollutants.

Photocatalytic technology is an attractive option for environmental remediation because of its green and sustainable nature. However, the inefficient utilization of solar energy and powder morphology currently impede its practical application. Here, we designed a floatable photocatalyst by anchoring 0D Cu2(OH)PO4 (CHP) nanoparticles on 2D graphene to construct 0D/2D CHP/reduced graphene oxide (rGO) aerogels. The CHP/rGO aerogels have interconnected mesopores that provide a large surface area, promoting particle dispersion and increasing the number of active sites. Moreover, the optical response of the CHP/rGO aerogel has been significantly expanded to cover the full spectrum of the solar light. Notably, the 20%CHP/rGO aerogel displayed a high degradation rate (k = 0.178 min-1) taking methylene blue (MB) as a model pollutant under light irradiation (λ > 420 nm). The enhanced photocatalytic activity is ascribed to the rapid electron transfer in the CHP/rGO heterostructures, as supported by the DFT theoretical calculations. Our research highlights the utilization of full spectrum responsive photocatalysts for the elimination of organic pollutants from wastewater under solar light irradiation, as well as the potential for catalyst recovery using floatable aerogels to meet industrial requirements.

Genome-wide profiling of DNA methylome and transcriptome reveals epigenetic regulation of Urechis unicinctus response to sulfide stress.

Sulfide is a well-known environmental pollutant that can have detrimental effects on most organisms. However, few metazoans living in sulfide-rich environments have developed mechanisms to tolerate and adapt to sulfide stress. Epigenetic mechanisms, including DNA methylation, have been shown to play a vital role in environmental stress adaptation. Nevertheless, the precise function of DNA methylation in biological sulfide adaptation remains unclear. Urechis unicinctus, a benthic organism inhabiting sulfide-rich intertidal environments, is an ideal model organism for studying adaptation to sulfide environments. In this study, we conducted a comprehensive analysis of the DNA methylome and transcriptome of U. unicinctus after exposure to 50 µM sulfide. The results revealed dynamic changes in the DNA methylation (5-methylcytosine) landscape in response to sulfide stress, with U. unicinctus exhibiting elevated DNA methylation levels following stress exposure. Integrating differentially expressed genes (DEGs) and differentially methylated regions (DMRs), we identified a crucial role of gene body methylation in predicting gene expression. Furthermore, using a DNA methyltransferase inhibitor, we validated the involvement of DNA methylation in the sulfide stress response and the gene regulatory network influenced by DNA methylation. The results indicated that by modulating DNA methylation levels during sulfide stress, the expression of glutathione S-transferase, glutamyl aminopeptidase, and cytochrome c oxidase could be up-regulated, thereby facilitating the metabolism and detoxification of exogenous sulfides. Moreover, DNA methylation was found to regulate and enhance the oxidative phosphorylation pathway, including NADH dehydrogenase, isocitrate dehydrogenase, and ATP synthase. Additionally, DNA methylation influenced the regulation of Cytochrome P450 and macrophage migration inhibitory factor, both of which are closely associated with oxidative stress and stress resistance. Our findings not only emphasize the role of DNA methylation in sulfide adaptation but also provide novel insights into the potential mechanisms through which marine organisms adapt to environmental changes.

Identification of the principal neuropeptide MIP and its action pathway in larval settlement of the echiuran worm Urechis unicinctus.

BACKGROUND: Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood. RESULTS: In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate. CONCLUSION: Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement.

Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

A role for Retinoblastoma 1 in hindbrain morphogenesis by regulating GBX family.

The hindbrain, which develops from the anterior end of the neural tube expansion, can differentiate into the metencephalon and myelencephalon, with varying sizes and functions. The midbrain-hindbrain boundary (MHB) and hindbrain myelencephalon/ventral midline (HMVM) are known to be the source of the progenitors for the anterior hindbrain and myelencephalon, respectively. However, the molecular networks regulating hindbrain morphogenesis in these structures remain unclear. In this study, we show that retinoblastoma 1 (rb1) is highly expressed at the MHB and HMVM in zebrafish. Knocking out rb1 in mice and zebrafish results in an enlarged hindbrain due to hindbrain neuronal hyperproliferation. Further study reveals that Rb1 controls the hindbrain morphogenesis by suppressing the expression of Gbx1/Gbx2, essential transcription factors for hindbrain development, through its binding to E2f3/Hdac1, respectively. Interestingly, we find that Gbx1 and Gbx2 are expressed in different types of hindbrain neurons, suggesting distinct roles in hindbrain morphogenesis. In summary, our study clarifies the specific role of RB1 in hindbrain neural cell proliferation and morphogenesis by regulating the E2f3-Gbx1 axis and the Hdac1-Gbx2 axis. These findings provide a research paradigm for exploring the differential proliferation of neurons in various brain regions.

Role of RB1 in neurodegenerative diseases: inhibition of post-mitotic neuronal apoptosis via Kmt5b.

During the development of the vertebrate nervous system, 50% of the nerve cells undergo apoptosis shortly after formation. This process is important for sculpting tissue during morphogenesis and removing transiently functional cells that are no longer needed, ensuring the appropriate number of neurons in each region. Dysregulation of neuronal apoptosis can lead to neurodegenerative diseases. However, the molecular events involved in activating and regulating the neuronal apoptosis program are not fully understood. In this study, we identified several RB1 mutations in patients with neurodegenerative diseases. Then, we used a zebrafish model to investigate the role of Rb1 in neuronal apoptosis. We showed that Rb1-deficient mutants exhibit a significant hindbrain neuronal apoptosis, resulting in increased microglia infiltration. We further revealed that the apoptotic neurons in Rb1-deficient zebrafish were post-mitotic neurons, and Rb1 inhibits the apoptosis of these neurons by regulating bcl2/caspase through binding to Kmt5b. Moreover, using this zebrafish mutant, we verified the pathogenicity of the R621S and L819V mutations of human RB1 in neuronal apoptosis. Collectively, our data indicate that the Rb1-Kmt5b-caspase/bcl2 axis is crucial for protecting post-mitotic neurons from apoptosis and provides an explanation for the pathogenesis of clinically relevant mutations.

Refinement of Specialized Nursing Intervention in Elderly Patients with Diabetes Complicated by Pulmonary Infection and the Impact on the Patient's Condition and Prognosis.

Objective: Our aim was to analyze the effect of refined specialized nursing intervention in elderly patients with diabetes and concurrent pulmonary infection and the impact on patients' conditions and outcomes. Methods: Clinical data from 87 elderly patients with type 2 diabetes (T2D) complicated by pulmonary infection treated in Lishui Municipal Central Hospital in China from February 2021 to February 2023 were retrospectively analyzed. All patients conformed to complete inclusion and exclusion criteria. Patients were divided into a control group (n=43) and an observation group (n=44) based on the nursing intervention they received. The control group received routine nursing intervention, while the observation group received refined specialized nursing intervention. The nursing intervention effects, hospitalization duration, disease knowledge acquisition, blood glucose indicators (fasting plasma glucose [FPG], 2-hour postprandial glucose [2hPG]), inflammatory marker indicators (C-reactive protein [CRP], heparin-binding protein [HBP]) levels, comfort levels and nursing satisfaction were compared between the 2 groups. Results: (1) Nursing intervention effect and hospitalization duration: The observation group showed significantly higher overall intervention effectiveness and notably shorter hospital stays compared with the control group (P < .05). (2) Disease knowledge acquisition and blood glucose indicator levels: Before the intervention, there were no significant differences in disease knowledge acquisition, FPG or 2hPG levels between the 2 groups (P > .05); after the intervention, the observation group exhibited significantly higher disease knowledge acquisition and lower FPG and 2hPG levels than the control group (P < .05). (3) Inflammatory marker indicator levels: Prior to the intervention, there were no significant differences in CRP or HBP levels between the 2 groups (P > .05); post-intervention, the observation group showed markedly lower CRP and HBP levels compared with the control group (P < .05). (4) Comfort levels: Prior to the intervention, there were no significant differences in physiological, psychological, environmental or social comfort scores between the 2 groups (P > .05); after the intervention, the observation group exhibited significantly higher scores in all comfort aspects compared with the control group (P < .05). (5) Nursing satisfaction: Nursing satisfaction in the control group was 74.42%, while in the observation group it was 90.91%, indicating significantly higher nursing satisfaction in the observation group (P < .05). Conclusion: Refined specialized nursing intervention significantly improved outcomes in elderly patients with diabetes and concurrent pulmonary infection. Compared with routine nursing intervention, refined specialized nursing intervention remarkably enhanced patient comfort during hospitalization, improved disease knowledge acquisition, rapidly adjusted blood glucose levels and reduced systemic inflammatory response, facilitating better patient recovery. Moreover, it moderately enhanced satisfaction for patients and their families, holding significant implications for promoting harmonious doctor-patient relationships, hence advocating for its clinical dissemination.

Study on the mechanism of S100A4-mediated cancer oncogenesis in uveal melanoma cells through the integration of bioinformatics and in vitro experiments.

BACKGROUND: The elevated metastasis rate of uveal melanoma (UM) is intricately correlated with patient prognosis, significantly affecting the quality of life. S100 calcium-binding protein A4 (S100A4) has tumorigenic properties; therefore, the present study investigated the impact of S100A4 on UM cell proliferation, apoptosis, migration, and invasion using bioinformatics and in vitro experiments. METHODS: Bioinformatic analysis was used to screen S100A4 as a hub gene and predict its possible mechanism in UM cells, and the S100A4 silencing cell line was constructed. The impact of S100A4 silencing on the proliferative ability of UM cells was detected using the Cell Counting Kit-8 and colony formation assays. Annexin V-FITC/PI double fluorescence and Hoechst 33342 staining were used to observe the effects of apoptosis on UM cells. The effect of S100A4 silencing on the migratory and invasive capabilities of UM cells was assessed using wound healing and Transwell assays. Western blotting was used to detect the expression of related proteins. RESULTS: The present study found that S100A4 is a biomarker of UM, and its high expression is related to poor prognosis. After constructing the S100A4 silencing cell line, cell viability, clone number, proliferating cell nuclear antigen, X-linked inhibitor of apoptosis protein, and survivin expression were decreased in UM cells. The cell apoptosis rate and relative fluorescence intensity increased, accompanied by increased levels of Bax and caspase-3 and decreased levels of Bcl-2. Additionally, a decrease in the cell migration index and relative invasion rate was observed with increased E-cadherin expression and decreased N-cadherin and vimentin protein expression. CONCLUSION: S100A4 silencing can inhibit the proliferation, migration, and invasion and synchronously induces apoptosis in UM cells.

Manipulating Hetero-Nanowire Films for Flexible and Multifunctional Thermoelectric Devices.

Flexible thermoelectric devices hold significant promise in wearable electronics owing to their capacity for green energy generation, temperature sensing, and comfortable wear. However, the simultaneous achievement of excellent multifunctional sensing and power generation poses a challenge in these devices. Here, ordered tellurium-based hetero-nanowire films are designed for flexible and multifunctional thermoelectric devices by optimizing the Seebeck coefficient and power factor. The obtained devices can efficiently detect both object and environment temperature, thermal conductivity, heat proximity, and airflow. In addition, combining the thermoelectric units with radiative cooling materials exhibits remarkable thermal management capabilities, preventing device overheating and avoiding degradation in power generation. Impressively, this multifunctional electronics exhibits excellent resistance in extreme low earth orbit environments. The fabrication of such thermoelectric devices provides innovative insights into multimodal sensing and energy harvesting.

Spectroscopic visualization of reversible hydrogen spillover between palladium and metal-organic frameworks toward catalytic semihydrogenation.

Hydrogen spillover widely occurs in a variety of hydrogen-involved chemical and physical processes. Recently, metal-organic frameworks have been extensively explored for their integration with noble metals toward various hydrogen-related applications, however, the hydrogen spillover in metal/MOF composite structures remains largely elusive given the challenges of collecting direct evidence due to system complexity. Here we show an elaborate strategy of modular signal amplification to decouple the behavior of hydrogen spillover in each functional regime, enabling spectroscopic visualization for interfacial dynamic processes. Remarkably, we successfully depict a full picture for dynamic replenishment of surface hydrogen atoms under interfacial hydrogen spillover by quick-scanning extended X-ray absorption fine structure, in situ surface-enhanced Raman spectroscopy and ab initio molecular dynamics calculation. With interfacial hydrogen spillover, Pd/ZIF-8 catalyst shows unique alkyne semihydrogenation activity and selectivity for alkynes molecules. The methodology demonstrated in this study also provides a basis for further exploration of interfacial species migration.

Polymer-Unit Graph: Advancing Interpretability in Graph Neural Network Machine Learning for Organic Polymer Semiconductor Materials.

The graph representation of complex materials plays a crucial role in the field of inorganic and organic materials investigations for developing data-centric materials science, such as those using graph neural networks (GNNs). However, the currently prevalent GNN models are primarily employed for investigating periodic crystals and organic small molecule data, yet they still encounter challenges in terms of interpretability and computational efficiency when applied to polymer monomers and organic macromolecules data. There is still a lack of graph representation of organic polymers and macromolecules specifically tailored for GNN models to explore the structural characteristics. The Polymer-unit Graph, a novel coarse-grained graph representation method introduced in study, is dedicated to expressing and analyzing polymers and macromolecules. By incorporating the Polymer-unit Graph into the GNN models and analyzing the organic semiconductor (OSC) materials database, it becomes possible to uncover intricate structure-property relationships involving branched-chain engineering, fluoridation substitution, and donor-acceptor combination effects on the elementary structure of OSC polymers. Furthermore, the Polymer-unit Graph enables visualizing the relationship between target properties and polymer units while reducing training time by an impressive 98% and minimizing molecular graph representation models. In conclusion, the Polymer-unit Graph successfully integrates the concept of Polymer-unit into the field of GNNs, enabling more accurate analysis and understanding of organic polymers and macromolecules.

WHO's Investigations and Studies, Unity Studies: A global initiative creating equitable opportunities for enhanced surveillance, operational research, capacity building, and global knowledge sharing.

The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.

Comprehensive Similarity Algorithm and Molecular Dynamics Simulation-Assisted Terahertz Spectroscopy for Intelligent Matching Identification of Quorum Signal Molecules (N-Acyl-Homoserine Lactones).

To investigate the mechanism of aquatic pathogens in quorum sensing (QS) and decode the signal transmission of aquatic Gram-negative pathogens, this paper proposes a novel method for the intelligent matching identification of eight quorum signaling molecules (N-acyl-homoserine lactones, AHLs) with similar molecular structures, using terahertz (THz) spectroscopy combined with molecular dynamics simulation and spectral similarity calculation. The THz fingerprint absorption spectral peaks of the eight AHLs were identified, attributed, and resolved using the density functional theory (DFT) for molecular dynamics simulation. To reduce the computational complexity of matching recognition, spectra with high peak matching values with the target were preliminarily selected, based on the peak position features of AHL samples. A comprehensive similarity calculation (CSC) method using a weighted improved Jaccard similarity algorithm (IJS) and discrete Fréchet distance algorithm (DFD) is proposed to calculate the similarity between the selected spectra and the targets, as well as to return the matching result with the highest accuracy. The results show that all AHL molecular types can be correctly identified, and the average quantization accuracy of CSC is 98.48%. This study provides a theoretical and data-supported foundation for the identification of AHLs, based on THz spectroscopy, and offers a new method for the high-throughput and automatic identification of AHLs.

Polaron interfacial entropy as a route to high thermoelectric performance in DAE-doped PEDOT:PSS films.

Enhancing the thermoelectric transport properties of conductive polymer materials has been a long-term challenge, in spite of the success seen with molecular doping strategies. However, the strong coupling between the thermopower and the electrical conductivity limits thermoelectric performance. Here, we use polaron interfacial occupied entropy engineering to break through this intercoupling for a PEDOT:PSS (poly(3,4-ethylenedioxythiophene)-poly(4-styrenesulfonate)) thin film by using photochromic diarylethene (DAE) dopants coupled with UV-light modulation. With a 10-fold enhancement of the thermopower from 13.5 µV K-1 to 135.4 µV K-1 and almost unchanged electrical conductivity, the DAE-doped PEDOT:PSS thin film achieved an extremely high power factor of 521.28 µW m-1 K-2 from an original value of 6.78 µW m-1 K-2. The thermopower was positively correlated with the UV-light intensity but decreased with increasing temperature, indicating resonant coupling between the planar closed DAE molecule and PEDOT. Both the experiments and theoretical calculations consistently confirmed the formation of an interface state due to this resonant coupling. Interfacial entropy engineering of polarons could play a critical role in enhancing the thermoelectric performance of the organic film.

Targeting TNF/IL-17/MAPK pathway in hE2A-PBX1 leukemia: effects of OUL35, KJ-Pyr-9, and CID44216842.

t(1;19)(q23;p13) is one of the most common translocation genes in childhood acute lymphoblastic leukemia (ALL) and is also present in acute myeloid leukemia (AML) and mixed-phenotype acute leukemia (MPAL). This translocation results in the formation of the oncogenic E2A-PBX1 fusion protein, which contains a trans-activating domain from E2A and a DNA-binding homologous domain from PBX1. Despite its clear oncogenic potential, the pathogenesis of E2A-PBX1 fusion protein is not fully understood (especially in leukemias other than ALL), and effective targeted clinical therapies have not been developed. To address this, we established a stable and heritable zebrafish line expressing human E2A-PBX1 (hE2APBX1) for high-throughput drug screening. Blood phenotype analysis showed that hE2APBX1 expression induced myeloid hyperplasia by increasing myeloid differentiation propensity of hematopoietic stem cells (HSPCs) and myeloid proliferation in larvae, and progressed to AML in adults. Mechanistic studies revealed that hE2A-PBX1 activated the TNF/IL-17/MAPK signaling pathway in blood cells and induced myeloid hyperplasia by upregulating the expression of the runx1. Interestingly, through high-throughput drug screening, three small molecules targeting the TNF/IL-17/MAPK signaling pathway were identified, including OUL35, KJ-Pyr-9, and CID44216842, which not only alleviated the hE2A-PBX1- induced myeloid hyperplasia in zebrafish but also inhibited the growth and oncogenicity of human pre-B ALL cells with E2A-PBX1. Overall, this study provides a novel hE2A-PBX1 transgenic zebrafish leukemia model and identifies potential targeted therapeutic drugs, which may offer new insights into the treatment of E2A-PBX1 leukemia.

High-Performance and Stable Perovskite X-ray Detection and Imaging Based on a Ti Cathode.

High-energy radiation detectors with a good imaging resolution, fast response, and high sensitivity are desired to operate at a high electric field. However, strong ion migration triggered by electrochemical reactions at the interface between a high-potential electrode and an organic-inorganic hybrid perovskite limits the stability of radiation detectors under a high electric field. Herein, we demonstrate that such ion migration could be effectively suppressed in devices with a Ti cathode, even at a high electric field of 50 V mm-1, through time-of-flight secondary-ion mass spectrometry. X-ray photoelectron spectroscopy illustrates that Ti-N bonds formed at the interface of MAPbBr3 perovskite single crystals/Ti electrode effectively inhibit the electrochemical reaction in organic-inorganic hybrid perovskite devices and ultimately improve the operating stability under a high electric field. The device with a Ti electrode reaches a high sensitivity of 96 ± 1 mC Gyair-1 cm-2 and a low detection limit of 2.8 ± 0.3 nGy s-1 under hard X-ray energy.

A 2PLM-RANK multidimensional forced-choice model and its fast estimation algorithm.

High-stakes non-cognitive tests frequently employ forced-choice (FC) scales to deter faking. To mitigate the issue of score ipsativity derived, many scoring models have been devised. Among them, the multi-unidimensional pairwise preference (MUPP) framework is a highly flexible and commonly used framework. However, the original MUPP model was developed for unfolding response process and can only handle paired comparisons. The present study proposes the 2PLM-RANK as a generalization of the MUPP model to accommodate dominance RANK format response. In addition, an improved stochastic EM (iStEM) algorithm is devised for more stable and efficient parameter estimation. Simulation results generally supported the efficiency and utility of the new algorithm in estimating the 2PLM-RANK when applied to both triplets and tetrads across various conditions. An empirical illustration with responses to a 24-dimensional personality test further supported the practicality of the proposed model. To further aid in the application of the new model, a user-friendly R package is also provided.

Aging CsPbBr3 Nanocrystal Wafer for Ultralow Ionic Migration and Environmental Stability for Direct X-ray Detection.

The outstanding photoelectric properties of perovskites demonstrate extreme promise for application in X-ray detection. However, the soft lattice of the perovskite results in severe ionic migration for three-dimensional materials, limiting the operation stability of perovskite X-ray detectors. Although ligand-decorated nanocrystals (NCs) exhibit significantly higher stability than three-dimensional perovskites, defects remaining on the interface of NCs could still trigger halide migration under a high bias due to the incomplete ligand decoration. Furthermore, it is still challenging to realize sufficient thickness of absorption layers based on NCs for X-ray detectors through traditional methods. Herein, we develop a centimeter-size and millimeter-thick wafer based on CsPbBr3 NCs through isostatic pressing for X-ray detectors, in which the interfacial defects of NCs are remedied by CsPb2Br5 during aging of wafer in ambient humidity. The wafer shows outstanding sensitivity (200 µC Gyair-1 cm-2) and ultralow dark current drift (1.78 × 10-8 nA cm-1 s-1 V-1 @ 400 V cm-1). Moreover, it shows storage stability with negligible performance degradation for 60 days in ambient humidity. Thus, aging perovskite NC wafers for X-ray detection holds huge potential for next-generation X-ray imaging plates.