Search Results (2,016)

Elucidating amyloid formation inside biomolecular condensates requires models that resolve (i) local, chemistry specific contacts controlling β registry and (ii) mesoscale phase behavior and cluster coalescence on microsecond timescales—capabilities beyond single resolution models. We present a hybrid united atom/coarse grained (UA–CG) force field coupling a PACE UA peptide model with the MARTINI CG framework. Cross resolution nonbonded parameters are first optimized against all atom side chain potentials of mean force to balance the relative strength between different types of interactions and then refined through universal parameter scaling by matching radius of gyration distributions for specific systems using. We applied this approach to simulate a recently reported model system comprising the LVFFAR₉ peptide that can co-assemble into amyloid fibrils via liquid–liquid phase separation. Our ten-microsecond simulations reveal rapid droplet formation populated by micelle like nanostructures with its inner core composed of LVFF clusters. The nanostructures can further fuse but the fusion is reaction-limited due to an electrostatic coalescence barrier. β structures emerge once clusters exceed ~10 peptides, and the LVFFAR₉ fraction modulates amyloid polymorphism, reversing parallel versus antiparallel registry at lower LVFFAR₉. These detailed insights generated from long simulations highlight the promise of our hybrid UA–CG strategy in investigating the molecular mechanism of condensate aging. Full article

Transcription is a core hallmark of cancer, wherein many different proteins assemble at specific sites in the nucleus and act in concert to transcribe functionally relevant genes. Central to this process are transcription factors that bind to their cognate DNA motifs on enhancers and super-enhancers to recruit cofactors, coactivators, and epigenetic modifiers, thereby inducing or repressing gene expression. Super-enhancers drive oncogenic transcription, to which cancer cells become highly addicted and confer tumor dependencies on super-enhancer-driven transcription machinery. Transcriptional condensates (TCs) are nuclear membrane-less assemblies of DNA-binding transcription factors, transcription co-activators, and the transcriptional machinery (such as RNA polymerases, non-coding RNAs) formed through liquid–liquid phase separation (LLPS). The function of transcriptionally active oncogenic proteins and their interplay with nucleic acids are carried out within these biomolecular condensates, allowing them to spatiotemporally regulate oncogene expression and lead to the induction and maintenance of cancer. With this growing understanding, specific inhibitors and strategies targeting TC assembly and activation should be considered promising therapeutic opportunities for treating various tumors, including hematological malignancies. Full article

Ti-bearing blast furnace slag (TBS), a byproduct of vanadium–titanium magnetite smelting, serves as an important secondary resource for titanium recovery. However, the complex mineralogical composition and finely dispersed nature of titanium in TBS present significant challenges for efficient extraction. This review systematically examines four major titanium extraction routes: hydrometallurgical leaching, pyrometallurgical smelting, molten salt electrolysis, and selective precipitation, focusing on their limitations and recent improvements. For instance, conventional acid leaching suffers from acid mist release, a colloidal formation that hinders titanium recovery, and waste acid pollution. The adoption of concentrated sulfuric acid roasting activation effectively suppresses acid mist emission and prevents colloidal generation. Pyrometallurgical approaches are hampered by high energy consumption and substantial carbon emissions, which can be alleviated through the use of gaseous reductants to enhance reaction efficiency and reduce environmental impact. Molten electrolysis faces issues such as polarization and undesirable dendritic deposition; these are mitigated by employing liquid metal cathodes integrated with vacuum distillation to achieve high-purity titanium products. Selective precipitation struggles with strict crystallization conditions and low separation efficiency, though advanced techniques like supergravity separation show improved extraction performance. We propose an integrated technical strategy termed “Online conditioning driven by waste heat-mineral phase reconstruction-directional crystallization-optimized liberation.” This approach utilizes the inherent waste heat of slag combined with electromagnetic stirring to enhance homogeneity and promote efficient titanium recovery, offering a sustainable and scalable solution for industrial TBS treatment. Full article

Fatty acid-binding proteins (FABPs) represent a superfamily of intracellular lipid chaperones essential for the transport of lipids and homeostatic lipid metabolism. Although well-known for their role in systemic metabolic diseases, emerging evidence has identified brain-expressed FABPs as core players in neurodegeneration. This review focuses on brain-expressed FABPs, synthesizing recent advancements that link their role in metabolic dysregulation to neurotoxicity. We present a system that integrates these proteins within a multi-tiered complex pathobiological system that involves: an advanced glial “meta-inflammation” paradigm; a novel view on proteotoxicity via liquid–liquid phase separation (LLPS); changes in the gut–brain axis; and an involvement in the regulation of ferroptosis. Additionally, we also discuss the emerging pharmacological pipeline, highlighting notable preclinical ligands and drawing important lessons from systemic disease first-in-class-targeted FABPs. These first-in-class therapies have successfully validated this target family in systemic diseases. Finally, we explore future therapeutic strategies, where we emphasize the challenges and the precision cell-type-specific delivery approaches to harness the full therapeutic potential of these pivotal proteins. Full article

Hexagonal boron nitride (h-BN) possesses a unique combination of a wide bandgap, high thermal conductivity, and chemical inertness, making it a key insulating and thermal management material for advanced electronics and nanocomposites. However, its intrinsic hydrophobicity and strong interlayer van der Waals forces severely limit exfoliation efficiency and dispersion stability, particularly in scalable liquid-phase processes. Here, we report a synergistic exfoliation strategy that integrates acid-induced hydroxylation with gallium (Ga) intercalation to achieve high-yield (>80%) production of ultrathin (<4 nm) hydrophilic h-BN nanosheets. Hydroxylation introduces abundant -OH groups, expanding interlayer spacing and significantly increasing surface polarity, while Ga intercalation leverages its native Ga₂O₃ shell to form strong interfacial interactions with hydroxylated basal planes. This oxide-mediated adhesion facilitates efficient layer separation under mild sonication, yielding nanosheets with well-preserved lateral dimensions and exceptional dispersion stability in polar solvents. Comprehensive characterization confirms the sequential chemical and structural modifications, revealing the crucial roles of hydroxylation-induced activation and Ga₂O₃ assisted wettability enhancement. This combined chemical activation–soft metallic intercalation approach provides a scalable, solution-processable route to high-quality h-BN nanosheets, opening new opportunities for their integration into dielectric, thermal interface, and multifunctional composite systems. Full article

Phase separation is one of the mechanisms critical for protein function, and its aberrances are associated with cancer development. However, mutations that affect protein phase separation and cancer development have not been systematically identified and analyzed. In this study, we systematically identified the mutations affecting protein liquid–liquid phase separation in multiple cancers. We calculated the phase separation scores alterations for over 1,200,000 mutations across 16 cancer types using the TCGA dataset. We then performed pathway enrichment, kinase, TF enrichment, and survival analysis to identify related biological processes and clinical implications. Nearly 10% of the mutations were defined to affect phase separation in pan-cancer. These mutations occupied a consistent percentage in each cancer type. Extremely influencing mutations accumulate on stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), and skin cutaneous melanoma (SKCM). Moreover, proteins carrying these mutations are enriched in cancer-related pathways, including TGF-beta signaling pathways and polycomb repressive complex. Phase separation of these proteins would be regulated by kinases, including CDK1, CDK2, and EGFR, and transcription factors, including ZNF407, ZNF318, and MGA proteins, to play functions in cancer. Protein–Protein Interaction Network revealed that these phase separation proteins are highly interconnected. Finally, patients carrying mutations that positively affect the protein phase separation are associated with poor prognosis in skin cutaneous melanoma (SKCM) and lung squamous cell carcinoma (LUSC), which could be partially explained by the pathogenicity of these mutations. The study provided a pan-cancer landscape for depicting the association of phase separation and cancer mutations, which would be a rich data resource for understanding the association of cancer mutations and phase separation. Full article

This work reports on a systematic investigation of the microstructure and comprehensive performance of Cu–Fe immiscible composite coatings prepared through the combination of mechanical alloying and laser cladding. The samples were characterized by scanning electron microscopy with an energy dispersive analysis, X-ray diffraction, a digital microhardness tester, a current tester, an electrochemical analyzer, and a magnetometer. The results show that the immiscible composite coatings are mainly composed of α-Fe particle dispersion in the ε-Cu matrix due to liquid phase separation, and this is exacerbated by the addition of more Fe content. Concentrated distribution of Fe-rich particles at either the top or bottom of the immiscible composite coatings is driven by the dominant mechanism of Marangoni and Stokes motion. With the increased fraction of Fe content, the microhardness and electrical resistivity increased, but with a degradation in corrosion resistance. With the increased ball milling time, the electrical resistivity increased, and the corrosion resistance improved. Compared to the medium-carbon steel substrate, the immiscible composite coatings can achieve an improved corrosion resistance, as well as a maximum saturated magnetization of 10.172 emu/g and the lowest coercivity at 17.249 Oe. Full article

Hospitals often use diatrizioic acid (DTZA), an iodinated radiocontrast agent, which is poorly biodegradable and persistent in aqueous media. Therefore, the objective of this work is to remove DTZA from water using an advanced separation process, namely liquid surfactant membrane (LSM) or emulsion liquid membrane. The LSM system is composed of Aliquat 336 as extractant, Span 80 as emulsifier, kerosene as diluent, and KCl as internal stripping phase. The impacts of experimental parameters impacting the extraction of DTZA from water by LSM, namely surfactant concentration, initial pH of the contaminated solution, extractant dosage, nature of base in the contaminated solution, concentration of the internal stripping phase, nature of stripping solution, emulsion/external solution volume ratio, internal solution/organic phase volume ratio, mixing rate, nature of diluent, emulsification time, emulsification rate, and initial DTZA concentration, were investigated. A highly stable emulsion with a good degree of removal of 90.8% of DTZA in water was obtained for an emulsifier dosage of 3% (w/w), an extractant dosage of 1.0% (w/w), a pH of the contaminated solution of 10 using NH₄OH, a concentration of the inner phase of 0.3 N KCl, an internal solution/organic phase volume ratio of 1/1, an emulsion/external solution volume ratio of 20/250, a mixing speed of 250 rpm, an emulsification time of 4 min, and an emulsification speed of 20,000 rpm. Additionally, the extraction of DTZA from various natural water matrices (natural mineral water, tap water and seawater) was examined. The developed LSM method offers a fascinating enhanced separation method for the elimination of DTZA in waters with low chloride ion concentrations. Full article

Polymer-dispersed liquid crystal (PDLC) smart windows hold significant potential for energy-efficient buildings and vehicles, offering a promising pathway toward carbon neutrality. However, their widespread applications are hindered by critical limitations, including high driving voltages and the inability to achieve programmable patterning or multi-region addressable control. To address these challenges, we propose a pre-orientation strategy via low-voltage electric field (5 V, 1 kHz), which optimizes liquid crystal molecular alignment during the phase separation process. Vertically aligned liquid crystal molecules in the polymer network with enlarged pore structures reduce anchoring energy barriers for LC molecular reorientation, causing a 61.2% reduction in threshold voltage (V_th) from 20.6 V to 8.0 V. Crucially, a programmable patterned PDLC film is successfully fabricated by utilizing cost-effective photomasks. Due to the different V_th of the corresponding regions, the patterned PDLC film exhibits stepwise control modes of light transmission: patterned scattering state, patterned transparent state and total transparent state, driven by incremental voltages. Our method can achieve not only energy-efficient tunable patterns for esthetic designs (e.g., logos or images) but also a scalable platform for multi-level optical modulation, which will advance PDLC technology toward low-voltage adaptive smart windows and open avenues for intelligent architectures and broadening their application scenarios. Full article

Liquid–liquid phase separation (LLPS) is a fundamental biophysical process in which proteins and nucleic acids dynamically demix from the cellular milieu to form membraneless organelles (MLO) with liquid-like properties. Environmental cues, such as light, temperature fluctuations, and pathogen interactions, induce LLPS of fungal proteins with intrinsically disordered regions (IDRs) or multimerization domains, thereby regulating fungal hyphal growth, sexual reproduction, pathogenesis, and adaptation. Recently, LLPS has emerged as a powerful tool for biomolecular research, innovative biotechnological application, biosynthesis and metabolic engineering. This review focuses on the current advances in environmental cue-triggered fungal condensates assembled by LLPS, with a focus on their roles in regulating the fungal physical biology and cellular processes including transcription, RNA modification, translation, posttranslational modification process (PTM), transport, and stress response. It further discusses the strategies of engineering synthetic biomolecular condensates in microbial cell factories to enhance production and metabolic efficiency. Full article

Liquid–liquid phase separation (LLPS) in cell biology has revolutionized our understanding of how cells organize biochemical reactions and structures through dynamic, membraneless organelles (MLOs). In neurons, LLPS-driven processes are particularly important for regulating synaptic plasticity, RNA metabolism, and responses to environmental stressors. Over the past decade, LLPS has gained increasing attention in neurobiology as a framework to interpret altered synaptic functions in various neurodevelopmental disorders (NDDs). These diseases comprise a diverse spectrum of clinical and pathological symptoms (e.g., global developmental delay, impaired cognitive and mental functions, as well as social withdrawal). Recent studies have highlighted how mutations in proteins containing intrinsically disordered regions (IDRs)—key drivers of LLPS—can alter condensate properties, resulting in persistent or defective MLO formation. These aberrant assemblies may disrupt RNA transport, splicing, and translation in developing neurons, thereby contributing to disorder pathology. IDRs are known to be enriched in membraneless components, such as stress granules, nuclear paraspeckles, and P-bodies, where they play crucial role in the formation, maintenance, and function of protein–RNA networks. This review explores the role of stress-induced MLOs in the nervous system, the molecular principles governing their formation, and how their dysfunction bridges the gap between environmental stress responses and neurodevelopmental impairment. Full article

The mammalian epidermis forms a critical barrier against environmental insults and water loss. The formation of its outermost layer, the stratum corneum, involves a rapid terminal differentiation process that has traditionally been explained by the “bricks and mortar” model. Recent advances reveal a more dynamic mechanism governed by intracellular liquid–liquid phase separation (LLPS). This review proposes that the lifecycle of the granular layer is orchestrated by LLPS. Evidence is synthesized showing that keratohyalin granules (KGs) are biomolecular condensates formed by the phase separation of the intrinsically disordered protein filaggrin (FLG). The assembly, maturation, and pH-triggered dissolution of these condensates are essential for cytoplasmic remodeling and the programmed flattening of keratinocytes, a process known as corneoptosis. In parallel, an LLPS-based signaling pathway is described in which the kinase RIPK4 forms condensates that activate the Hippo pathway, promoting transcriptional reprogramming and differentiation. Together, these structural and signaling condensates drive skin barrier formation. This review further reinterprets atopic dermatitis, ichthyosis vulgaris, and Bartsocas-Papas syndrome as diseases of aberrant phase behavior, in which pathogenic mutations alter condensate formation or material properties. This integrative framework offers new insight into skin biology and suggests novel opportunities for therapeutic intervention through biophysics-informed biomaterial and regenerative design. Full article

This study explores the application of phosphonium-based ionic liquids (ILs) for the efficient separation of valeric acid (VA) through reactive liquid–liquid extraction. Two hydrophobic quaternary phosphine ILs, trihexyl(tetradecyl)phosphonium decanoate (C103) and trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate (C104), were evaluated in combination with heptane as a diluent. Extraction efficiency was experimentally determined at different levels of extraction process factors in terms of aqueous phase pH (3–6), IL concentration (0–120 g/L), and process temperature (25–60 °C). For each IL, extraction efficiency was predicted using a response surface regression model, and the process factors were optimized based on the desirability function approach. Both ILs effectively extracted VA, with optimal mean values of extraction efficiency of 98.61% for C103 and 99.24% for C104 under optimal conditions (pH of 3.8 and 4, respectively, IL concentration of 60 g/L, and temperature of 25 °C). Mechanistic analysis revealed that VA extraction occurs through the formation of IL-acid complexes, involving hydrogen bonding between the non-dissociated acid and the IL anion. Depending on the extractant concentration, 1:1 and 2:1 acid-to-IL stoichiometric ratios were observed. These findings highlight the potential of phosphonium-based ILs, particularly in a heptane-diluted system, as high-performance extractants for carboxylic acid separation. Full article

Conventional methods for testing steroids and hormones (SHs) in environmental samples are exhaustive, complex, and score poorly in sustainability matrices. Therefore, this study evaluates the automated sample preparation approach using the modular Biomek i7 Workstation for the analysis of 27 SHs in wastewater. Method development involved optimizing Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) parameters, preparing wastewater matrix blank, and assessing extraction efficiency using three solid phase extraction (SPE) cartridges. Extraction efficiency trials showed suitability in the order of Hydrophilic–Lipophilic Balance (HLB) > Mixed-Mode Cation Exchange (MCX) > Mixed-Mode Anion Exchange (MAX). The method demonstrated specificity for all targeted SHs, with Cholesterol showing a maximum interfering peak of 17.71% of the quantification limit (LOQ). The method met matrix effect tolerance of ±20% for 26 SHs, while Epi Coprostanol (34.92%) showed signal enhancement >20%. The 8-point calibration curve plotted using automated extraction demonstrated acceptable linearity across the tested range. Spiked studies at low (LQC), middle (MQC), and higher (HQC) quality control (QC) levels (n = 6, repeated on three separate occasions) demonstrated % RSD values within 20% and recoveries ranging from 71.54% to 115.00%. The method met validation criteria, showing reliability in Intra-Laboratory Comparison (ILC) and Blind Testing (BT). The method outperformed the conventional approach in greenness assessment (Complex Modified Green Analytical Procedure Index) and practicality evaluation (Blue Applicability Grade Index), offering an effective and sustainable protocol for environmental testing laboratories. Full article

Zeolites and metal–organic frameworks (MOFs) are crystalline porous materials characterized by highly ordered pore structures. Their fabrication into membranes has demonstrated significant potential for use in separation processes involving liquids or gases. Traditional methods for synthesizing these membranes often require prolonged reaction times and high energy input. In contrast, microwave heating technology has gained increasing attention as a more efficient approach for the synthesis of zeolite and MOF membranes, offering advantages such as rapid and uniform heating, enhanced energy efficiency, and greater environmental sustainability. This review focuses on fundamental research and laboratory-scale studies on the microwave-assisted synthesis of zeolite and MOF membranes. It begins by outlining the principles of microwave heating, emphasizing the mechanisms that enable accelerated heating. The discussion then highlights the key features and advantages of microwave synthesis in membrane fabrication, including reduced synthesis times, thinner membrane layers, suppression of impurities and undesired phases, and enhanced membrane density. Recent advancements in this area are also presented, particularly strategies for optimizing microwave heating processes, such as the use of single-mode microwave systems and precise control of heating rates. Notably, optimized microwave synthesis with controlled heating rates has been shown to reduce crystallization time by approximately 69%, decrease membrane thickness by nearly 70%, and improve pervaporation flux for acetic acid dehydration by more than 70%, compared with conventional microwave synthesis of mordenite membranes. Finally, the review summarizes and presents future perspectives aimed at promoting continued research and refinement of synthesis strategies in this promising area. Full article