Synergistic barium titanate/MXene composite as a high-performance piezo-photocatalyst for efficient dye degradation.

Piezo-photocatalysis combines photocatalysis and piezoelectric effects to enhance catalytic efficiency by creating an internal electric field in the photocatalyst, improving carrier separation and overall performance. This study presents a high-performance piezo-photocatalyst for efficient dye degradation using a synergistic barium titanate (BTO)-MXene composite. The composite was synthesized via a facile method, combining the unique properties of BTO nanoparticles with the high conductivity of MXene. The structural and morphological analysis confirmed the successful formation of the composite, with well-dispersed BTO nanoparticles on the MXene surface. The piezo-photocatalytic activity of the composite was evaluated using a typical dye solution (Rhodamine B: RhB) under ultraviolet irradiation and mechanical agitation. The results revealed a remarkable enhancement in dye degradation (90 % in 15 min for piezo-photocatalysis) compared to individual stimuli (58.2 % for photocatalysis and 95.8 % in 90 min for piezocatalysis), highlighting the synergistic effects between BTO and MXene. The enhanced catalytic performance was attributed to the efficient charge separation and transfer facilitated by the composite's structure, leading to increased reactive species generation and dye molecule degradation. Furthermore, the composite exhibited excellent stability and reusability, showcasing its potential for practical applications in wastewater treatment. Overall, this work represents a promising strategy for designing high-performance synergistic catalysts, addressing the pressing need for sustainable solutions in environmental remediation.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/ß-catenin signaling.

Perfluoroundecanoic acid (PFDA) is extensively utilized in the textile and food processing industries and may have a tumor-promoting effect by modulating the tumor microenvironment. Macrophages play crucial roles in tumor microenvironment as key regulators of tumor immunity. However, further investigation is needed to elucidate how PFDA interacts with macrophages and contributes to tumor progression. In this study, we treated the macrophage cell line RAW264.7 with various concentrations of PFDA and found that RAW264.7 transitioned into an M2 tumor-promoting phenotype. Through bioinformatic analysis and subsequent verification of molecular assays, we uncovered that PFDA could activate ß-catenin and enhance its nuclear translocation. Additionally, it was also observed that inhibiting ß-catenin nuclear translocation partly attenuated RAW264.7 M2 polarization induced by PFDA. The conditioned medium derived from PFDA-pretreated RAW264.7 cells significantly promoted the migration and invasion abilities of human ovarian cancer cells. Furthermore, in vivo studies corroborated that PFDA-pretreated RAW264.7 could promote tumor metastasis, which could be mitigated by pretreatment with the ß-catenin inhibitor ICG001. In conclusion, our study demonstrated that PFDA could promote cancer metastasis through regulating macrophage M2 polarization in a Wnt/ß-catenin-dependent manner.

Synergistic effect of protein foams and polysaccharide on the invisible hemostasis of acellular dermal matrix sponges.

Efficient management of hemorrhage is vital for preventing hemorrhagic shock and safeguarding wounds against infection. Inspired by the traditional Chinese steamed bread-making process, which involves kneading, foaming, and steaming, we devised a hemostatic sponge by amalgamating an acellular dermal matrix gel, hydroxyethyl starch, and rice hydrolyzed protein. The integration of hydroxyethyl starch bolstered the sponge's mechanical and hemostatic attributes, while the inclusion of rice hydrolyzed protein, acting as a natural foaming agent, enhanced its porosity This augmentation facilitated rapid blood absorption, accelerated clot formation, and stimulated the clotting cascade. Experimental findings underscore the exceptional biocompatibility and physicochemical characteristics of the hemostatic sponge, positioning it on par with commercially available collagen hemostatic sponges for hemorrhage control. Mechanistically, the sponge fosters aggregation and activation of red blood cells and platelets, expediting coagulation kinetics both in vivo and in vitro. Notably, this hemostatic sponge activates the clotting cascade sans crosslinking agents, offering a premium yet cost-effective biomaterial with promising clinical applicability.

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

Enhancing the Thermoelectric and Mechanical Properties of p-Type PbS through Band Convergence and Microstructure Regulation.

While lead sulfide shows notable thermoelectric properties, its production costs remain high, and its mechanical hardness is low, which constrains its commercial viability. Herein, we demonstrate a straightforward and cost-effective method to produce PbS nanocrystals at ambient temperature. By introducing controlled amounts of silver, we achieve p-type conductivity and fine-tune the energy band structure and lattice configuration. Computational results show that silver shifts the Fermi level into the valence band, facilitating band convergence and thereby enhancing the power factor. Besides, excess silver is present as silver sulfide, which effectively diminishes the interface barrier and enhances the Seebeck coefficient. Defects caused by doping, along with dislocations and interfaces, reduce thermal conductivity to 0.49 W m-1 K-1 at 690 K. Moreover, the alterations in crystal structure and chemical composition enhance the PbS mechanical properties. Overall, optimized materials show thermoelectric figures of merit approximately 10-fold higher than that of pristine PbS, alongside an average hardness of 1.08 GPa.

Self-supported porous wood carbon electrode with a MoC/carbon nanocage composite for application in a high-performance supercapacitor.

The rational design and synthesis of carbon nanocages with highly complex porous structures are continuously facing challenges in the development of high-performance supercapacitors (SCs). The electrochemical performance characteristics of electrodes rely on their compositions and fabrication methods. Here, we propose a universal and efficient approach for the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8) on porous carbonized wood, where the selective utilization of hexacarbonyl molybdenum protects the structural integrity of the ZIF-8 precursor, preventing collapse during thermal treatment. The subsequent pyrolysis process leads to the formation of small-sized molybdenum carbide (MoC) which are embedded in carbon nanocages (CN). The composite electrode consists of MoC/CN embedded in a porous carbonized wood (PCW), and it shows area-specific capacity of 9.7F cm-2 and 9.4 F cm-2 at 5 mA cm-2 and 30 mA cm-2, respectively. Subsequently, the symmetric supercapacitor, with two MoC/CN@PCW electrodes exhibits a areal specific capacitance of 2.7 F cm-2 at 5 mA cm-2. Moreover, this supercapacitor maintains an capacitance retention rate of 98.5 % after 12,000 discharge cycles. The supercapacitor exhibits a power density of 6.5 mW cm-2, resulting in an energy density of 0.864 mWh cm-2. Therefore, the utilization of wood-based electrodes holds promise for energy storage systems.

CD169+ Skin Macrophages Function as a Specialized Subpopulation in Promoting Psoriasis-like Skin Disease in Mice.

Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.

Engineering of Thermoelectric Composites Based on Silver Selenide in Aqueous Solution and Ambient Temperature.

The direct, solid state, and reversible conversion between heat and electricity using thermoelectric devices finds numerous potential uses, especially around room temperature. However, the relatively high material processing cost limits their real applications. Silver selenide (Ag2Se) is one of the very few n-type thermoelectric (TE) materials for room-temperature applications. Herein, we report a room temperature, fast, and aqueous-phase synthesis approach to produce Ag2Se, which can be extended to other metal chalcogenides. These materials reach TE figures of merit (zT) of up to 0.76 at 380 K. To improve these values, bismuth sulfide (Bi2S3) particles also prepared in an aqueous solution are incorporated into the Ag2Se matrix. In this way, a series of Ag2Se/Bi2S3 composites with Bi2S3 wt % of 0.5, 1.0, and 1.5 are prepared by solution blending and hot-press sintering. The presence of Bi2S3 significantly improves the Seebeck coefficient and power factor while at the same time decreasing the thermal conductivity with no apparent drop in electrical conductivity. Thus, a maximum zT value of 0.96 is achieved in the composites with 1.0 wt % Bi2S3 at 370 K. Furthermore, a high average zT value (zTave) of 0.93 in the 300-390 K range is demonstrated.

Organizational culture and turnover intention among primary care providers: a multilevel study in four large cities in China.

BACKGROUND: Primary health care plays an important role in providing populations with access to health care. However, it is currently facing unprecedented workforce shortages and high turnover worldwide. OBJECTIVE: This study examined the relationship between organizational culture and turnover intention among primary care providers in China. METHODS: A cross-sectional survey was administered in four large cities in China, Tianjin, Jinan, Shanghai, and Shenzhen, comprising 38 community health centers and 399 primary care providers. Organizational culture was measured using the Competing Value Framework model, which is divided into four culture types: group, development, hierarchy, and rational culture. Turnover intention was measured using one item assessing participants' intention to leave their current position in the following year. We compared the turnover intention among different organizational culture types using a Chi-square test, while the hierarchical logistic regression was used to examine the relationship between organizational culture and turnover intention. RESULTS: The study found that 32% of primary care providers indicated an intention to leave. Primary care providers working in a hierarchical culture reported higher turnover intention (43.18%) compared with those in other cultures (p < 0.05). Hierarchical culture was a predictor of turnover intention (OR = 3.453, p < 0.001), whereas rational culture had a negative effect on turnover intention (OR = 0.319, p < 0.05). CONCLUSIONS: Our findings inform organizational management strategies to retain a healthy workforce in primary health care.

Main findings: This study found that primary care physicians and nurses working in a hierarchical culture are more likely to report the intention to leave compared to other culture types, while those working in a rational culture are significantly less likely to report the intention to leave.Added knowledge: The dominant organizational culture identified in community health centers across eastern China is group culture, and organizational culture is a significant predictor of the turnover intention of primary care providers.Global health impact for policy and action: Future primary care reform should focus on managerial interventions in their efforts to retain health workers and, in particular, develop and implement strategies to cultivate and moderate rational culture.

Physiological and transcriptome analysis of changes in endogenous hormone and sugar content during the formation of tender asparagus stems.

Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment have shown promising results, multicentre randomised controlled phase II clinical trials remain uncommon. The primary aim of this trial is to assess the safety and efficacy of different MSCs treatment courses for ACLF. METHODS AND ANALYSIS: This is a multicentre, double-blind, two-stage, randomised and placebo-controlled clinical trial. In the first stage, 150 patients with ACLF will be enrolled and randomly assigned to either a control group (50 cases) or an MSCs treatment group (100 cases). They will receive either a placebo or umbilical cord-derived MSCs (UC-MSCs) treatment three times (at weeks 0, 1 and 2). In the second stage, 28 days after the first UC-MSCs infusion, surviving patients in the MSCs treatment group will be further randomly divided into MSCs-short and MSCs-prolonged groups at a 1:1 ratio. They will receive two additional rounds of placebo or UC-MSCs treatment at weeks 4 and 5. The primary endpoints are the transplant-free survival rate and the incidence of treatment-related adverse events. Secondary endpoints include international normalised ratio, total bilirubin, serum albumin, blood urea nitrogen, model for end-stage liver disease score and Child-Turcotte-Pugh score. ETHICS AND DISSEMINATION: Ethical approval of this study has been obtained from the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-3-19-1). All results of the study will be submitted to international journals and international conferences for publication on completion of the study. TRIAL REGISTRATION NUMBER: NCT05985863.

Validation of the FIGO2023 staging system for early-stage endometrial cancer.

BACKGROUND: In 2023, the International Federation of Gynecology and Obstetrics (FIGO) updated the endometrial cancer staging system (FIGO2023). Our study aimed to validate the prognostic value of FIGO2023 in patients with early-stage EC (Stage I and Stage II). METHODS: After screening eligible EC patients from the Surveillance, Epidemiology and End Results (SEER) database, Kaplan-Meier cancer-specific survival (CSS) curves were used to evaluate the prognosis of patients with different stages. In addition, AUC, C-index, Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and Decision curve analysis (DCA) were used to comprehensively compare the efficacy of the new and the old staging system in predicting prognosis. RESULTS: A total of 33,156 patients were enrolled. The introduction of FIGO2023 significantly increased the proportion of stage II patients from 5.53 % to 24.76 %. The FIGO2023 defines different substages for patients, which show significant differences in CSS. Compared with FIGO2009, FIGO2023 performed better in discrimination, goodness of fit and clinical decision making. CONCLUSION: Compared with FIGO2009, FIGO2023 had a higher accuracy in predicting CSS in patients with early-stage EC in the SEER database.

An Asymmetric NIR-II Organic Fluorophore with an Ultra-Large Stokes Shift for Imaging-Guided and Targeted Phototherapy.

NIR-II imaging-guided phototherapy is an attractive, yet challenging, tumor treatment strategy. By monitoring the accumulation of phototherapy reagents at the tumor site through imaging and determining the appropriate therapy window, the therapeutic effect could be significantly improved. Probes with NIR-II (1000-1700 nm) fluorescence emission and a large Stokes shift hold great promise for fluorescence imaging with deep penetration, minimized self-quenching, and high spatiotemporal resolution. However, due to the lack of a suitable molecular framework, the design of a simple small-molecule dye with a large Stokes shift and NIR-II fluorescence emission has rarely been reported. Herein, we prepare an asymmetric D-π-A type NIR-II fluorescence probe (TBy). The probe is incapsulated in an amphiphilic polymer and modified with a fibronectin targeting peptide CREKA, which could recognize the fibrin-fibronectin complex overexpressed in multiple malignant tumors. The nanoparticles thus constructed (TByC-NPs) have maximum fluorescence emission at 1037 nm with a large Stokes shift of 426 nm, which is the largest Stokes shift among organic NIR-II fluorescent dyes reported in the literature. The TByC-NPs exhibit a good NIR-II imaging performance, active tumor targeting, and good photothermal and photodynamic capabilities. In vitro and in vivo studies verify that the TByC nanoplatform shows outstanding biocompatibility for NIR-II imaging-guided phototherapy and provides an excellent antitumor effect.

Multi-Interface Engineering of MXenes for Self-Powered Wearable Devices.

Self-powered wearable devices with integrated energy supply module and sensitive sensors have significantly blossomed for continuous monitoring of human activity and the surrounding environment in healthcare sectors. The emerging of MXene-based materials has brought research upsurge in the fields of energy and electronics, owing to their excellent electrochemical performance, large surface area, superior mechanical performance, and tunable interfacial properties, where their performance can be further boosted via multi-interface engineering. Herein, a comprehensive review of recent progress in MXenes for self-powered wearable devices is discussed from the aspects of multi-interface engineering. The fundamental properties of MXenes including electronic, mechanical, optical, and thermal characteristics are discussed in detail. Different from previous review works on MXenes, multi-interface engineering of MXenes from termination regulation to surface modification and their impact on the performance of materials and energy storage/conversion devices are summarized. Based on the interfacial manipulation strategies, potential applications of MXene-based self-powered wearable devices are outlined. Finally, proposals and perspectives are provided on the current challenges and future directions in MXene-based self-powered wearable devices.

Dose Optimization in Oncology Drug Development: An International Consortium for Innovation and Quality in Pharmaceutical Development White Paper.

The landscape of oncology drug development has witnessed remarkable advancements over the last few decades, significantly improving clinical outcomes and quality of life for patients with cancer. Project Optimus, introduced by the U.S. Food and Drug Administration, stands as a groundbreaking endeavor to reform dose selection of oncology drugs, presenting both opportunities and challenges for the field. To address complex dose optimization challenges, an Oncology Dose Optimization IQ Working Group was created to characterize current practices, provide recommendations for improvement, develop a clinical toolkit, and engage Health Authorities. Historically, dose selection for cytotoxic chemotherapeutics has focused on the maximum tolerated dose, a paradigm that is less relevant for targeted therapies and new treatment modalities. A survey conducted by this group gathered insights from member companies regarding industry practices in oncology dose optimization. Given oncology drug development is a complex effort with multidimensional optimization and high failure rates due to lack of clinically relevant efficacy, this Working Group advocates for a case-by-case approach to inform the timing, specific quantitative targets, and strategies for dose optimization, depending on factors such as disease characteristics, patient population, mechanism of action, including associated resistance mechanisms, and therapeutic index. This white paper highlights the evolving nature of oncology dose optimization, the impact of Project Optimus, and the need for a tailored and evidence-based approach to optimize oncology drug dosing regimens effectively.

Enhanced Piezocatalytic Performance of Li-doped BaTiO3 Through a Facile Sonication-Assisted Precipitation Approach.

Piezocatalysis-induced dye degradation has garnered significant attention as an effective method for addressing wastewater treatment challenges. In our study, we employed a room-temperature sonochemical method to synthesize piezoelectric barium titanate nanoparticles (BaTiO3: BTO) with varying levels of Li doping. This approach not only streamlined the sample preparation process but also significantly reduced the overall time required for synthesis, making it a highly efficient and practical method. One of the key findings was the exceptional performance of the Li-doped BTO nanoparticles. With 20 mg of Li additive, we achieved 90 % removal of Rhodamine B (RhB) dye within a relatively short timeframe of 150 minutes, all while subjecting the sample to ultrasonic vibration. This rapid and efficient dye degradation was further evidenced by the calculated kinetic rate constant, which indicated seven times faster degradation rate compared to pure BTO. The enhanced piezoelectric performance observed in the Li-doped BTO nanoparticles can be attributed to the strategic substitution of Li atoms, which facilitated a more efficient transfer of charge charges at the interface. Overall, our study underscores the potential of piezocatalysis coupled with advanced materials like Li-doped BTO nanoparticles as a viable and promising solution for wastewater treatment, offering both efficiency and environmental sustainability.

Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking.

Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables-alcohol consumption and problematic alcohol use-and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses. Our meta-analysis encompassed 64 published and 151 de novo MR analyses across 76 distinct primary outcomes. Results show that a genetic predisposition to alcohol consumption, independent of smoking, significantly correlates with a decreased risk of Parkinson's disease, prostate hyperplasia, and rheumatoid arthritis. It was also associated with an increased risk of chronic pancreatitis, colorectal cancer, and head and neck cancers. Additionally, a genetic predisposition to problematic alcohol use is strongly associated with increased risks of alcoholic liver disease, cirrhosis, both acute and chronic pancreatitis, and pneumonia. Evidence from our MR study supports the notion that alcohol consumption and problematic alcohol use are causally associated with a range of diseases, predominantly by increasing the risk.

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.

Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.

Insight into the ordering process and ethanol oxidation performance of Au-Pt-Cu ternary alloys.

Direct ethanol fuel cells (DEFCs), which have been widely recognized as nontoxic and green energy conversion devices, show attractive application prospects for liquid hydrogen-carriers, due to the higher specific energy and lower toxicity of ethanol. Pt-based catalysts are widely used in DEFCs, while their poor poisoning resistance highlights the importance of composition and structure optimization. Herein, we synthesized a series of reduced graphene oxide supported ternary alloy AuxPt1-xCu3/rGO (x = 0-1) catalysts with excellent ethanol oxidation performance and a composition-dependent volcano plot trend of the ordering degree was observed and rationalized. The highest Pt-normalized mass activity of Au0.8Pt0.2Cu3/rGO is attributed to the optimized CO binding energy according to DFT calculations. This work not only provides an efficient EOR catalyst based on ordered alloys AuxPt1-xCu3 (x = 0-1), but also offers valuable insight into the role of a third metal in tuning the structure and function of alloys.