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1.
J Environ Sci (China) ; 149: 149-163, 2025 Mar.
Article in English | MEDLINE | ID: mdl-39181630

ABSTRACT

Developing heterojunction photocatalyst with well-matched interfaces and multiple charge transfer paths is vital to boost carrier separation efficiency for photocatalytic antibiotics removal, but still remains a great challenge. In present work, a new strategy of chloride anion intercalation in Bi2O3 via one-pot hydrothermal process is proposed. The as-prepared Ta-BiOCl/Bi24O31Cl10 (TBB) heterojunctions are featured with Ta-Bi24O31Cl10 and Ta-BiOCl lined shoulder-by-shouleder via semi-coherent interfaces. In this TBB heterojunctions, the well-matched semi-coherent interfaces and shoulder-by-shoulder structures provide fast electron transfer and multiple transfer paths, respectively, leading to enhanced visible light response and improved photogenerated charge separation. Meanwhile, a type-II heterojunction for photocharge separation has been obtained, in which photogenerated electrons are drove from the CB (conduction band) of Ta-Bi24O31Cl10 to the both of bilateral empty CB of Ta-BiOCl and gathered on the CB of Ta-BiOCl, while the photogenerated holes are left on the VB (valence band) of Ta-Bi24O31Cl10, effectively hindering the recombination of photogenerated electron-hole pairs. Furthermore, the separated electrons can effectively activate dissolved oxygen for the generation of reactive oxygen species (·O2-). Such TBB heterojunctions exhibit remarkably superior photocatalytic degradation activity for tetracycline hydrochloride (TCH) solution to Bi2O3, Ta-BiOCl and Ta-Bi24O31Cl10. This work not only proposes a Ta-BiOCl/Bi24O31Cl10 shoulder-by-shoulder micro-ribbon architectures with semi-coherent interfaces and successive type-II heterojunction for highly efficient photocatalytic activity, but offers a new insight into the design of highly efficient heterojunction through phase-structure synergistic transformation strategy.


Subject(s)
Anti-Bacterial Agents , Bismuth , Water Pollutants, Chemical , Bismuth/chemistry , Anti-Bacterial Agents/chemistry , Water Pollutants, Chemical/chemistry , Catalysis , Photochemical Processes
2.
Methods Mol Biol ; 2856: 293-308, 2025.
Article in English | MEDLINE | ID: mdl-39283460

ABSTRACT

In order to analyze the three-dimensional genome architecture, it is important to simulate how the genome is structured through the cell cycle progression. In this chapter, we present the usage of our computation codes for simulating how the human genome is formed as the cell transforms from anaphase to interphase. We do not use the global Hi-C data as an input into the genome simulation but represent all chromosomes as linear polymers annotated by the neighboring region contact index (NCI), which classifies the A/B type of each local chromatin region. The simulated mitotic chromosomes heterogeneously expand upon entry to the G1 phase, which induces phase separation of A and B chromatin regions, establishing chromosome territories, compartments, and lamina and nucleolus associations in the interphase nucleus. When the appropriate one-dimensional chromosomal annotation is possible, using the protocol of this chapter, one can quantitatively simulate the three-dimensional genome structure and dynamics of human cells of interest.


Subject(s)
Anaphase , Chromatin , Genome, Human , Interphase , Humans , Anaphase/genetics , Interphase/genetics , Chromatin/genetics , Chromatin/metabolism , Computer Simulation , Chromosomes, Human/genetics , Mitosis/genetics
3.
Protein Expr Purif ; 225: 106583, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39168394

ABSTRACT

In recombinant protein purification, differences in isoelectric point (pI)/surface charge and hydrophobicity between the product and byproducts generally form the basis for separation. For bispecific antibodies (bsAbs), in many cases the physicochemical difference between product and byproducts is subtle, making byproduct removal considerably challenging. In a previous report, with a bsAb case study, we showed that partition coefficient (Kp) screening for the product and byproducts under various conditions facilitated finding conditions under which effective separation of two difficult-to-remove byproducts was achieved by anion exchange (AEX) chromatography. In the current work, as a follow-up study, we demonstrated that the same approach enabled identification of conditions allowing equally good byproduct removal by mixed-mode chromatography with remarkably improved yield. Results from the current and previous studies proved that separation factor determination based on Kp screening for product and byproduct is an effective approach for finding conditions enabling efficient and maximum byproduct removal, especially in challenging cases.


Subject(s)
Antibodies, Bispecific , Recombinant Proteins , Antibodies, Bispecific/chemistry , Antibodies, Bispecific/isolation & purification , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Chromatography, Ion Exchange/methods , Humans
4.
Food Chem ; 462: 141024, 2025 Jan 01.
Article in English | MEDLINE | ID: mdl-39217751

ABSTRACT

With the aim of expanding the potential application scope of mulberries, eleven pH-switchable deep eutectic solvents were screened for the ultrasonic-assisted extraction of mulberry polysaccharides, and a salt/salt aqueous two-phase system was constructed for the efficient separation of mulberry polysaccharides by regulating the system pH. DES-9 (tetraethylammonium chloride: octanoic acid molar ratio = 1: 2) with a critical response pH value of approximately 6.1 was concluded to be the best extraction solvent for extracting mulberry polysaccharides. A maximum polysaccharide extraction yield of 270.71 mg/g was obtained under the optimal conditions. The maximum polysaccharide extraction efficiency was 78.09 % for the pH-driven tetraethylammonium chloride/K2HPO4 aqueous two-phase system. An acidic ß-pyran mulberry polysaccharide with a low-molecular weight of 9.26 kDa and a confirmed monosaccharide composition were obtained. This efficient and environmentally friendly polysaccharide separation method offers a new approach for the efficient extraction and utilization of other plant polysaccharides.


Subject(s)
Deep Eutectic Solvents , Morus , Plant Extracts , Polysaccharides , Morus/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Hydrogen-Ion Concentration , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Deep Eutectic Solvents/chemistry , Chemical Fractionation/methods , Molecular Weight , Fruit/chemistry , Sodium Chloride/chemistry
5.
Methods Mol Biol ; 2855: 315-339, 2025.
Article in English | MEDLINE | ID: mdl-39354316

ABSTRACT

Octadecanoids are a subset of oxylipins derived from 18-carbon fatty acids. These compounds have historically been understudied but have more recently attracted attention to their purported biological activity. One obstacle to the study of octadecanoids has been a lack of specific analytical methods for their measurement. A particular limitation has been the need for chiral-based methods that enable separation and quantification of individual stereoisomers. The use of chirality provides an additional dimension for distinguishing analytes produced enzymatically from those formed through autoxidation. In this chapter, we describe a comprehensive method using chiral supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) for the quantification of octadecanoids in human plasma. This method stands as an effective approach for quantifying octadecanoids and is applicable to diverse research applications including clinical research.


Subject(s)
Chromatography, Supercritical Fluid , Tandem Mass Spectrometry , Chromatography, Supercritical Fluid/methods , Humans , Tandem Mass Spectrometry/methods , Stereoisomerism , Oxylipins/blood , Oxylipins/chemistry
6.
J Colloid Interface Sci ; 677(Pt B): 583-596, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39154450

ABSTRACT

HYPOTHESIS: An innovative strategy for designing high-performance demulsifiers is proposed. It hypothesizes that integrating mesoscopic molecular simulations with macroscopic physicochemical experiments can enhance the understanding and effectiveness of demulsifiers. Specifically, it is suggested that amphiphilic hyperbranched polyethyleneimine (CHPEI) could act as an efficient demulsifier in oil-water systems, with its performance influenced by its adsorption behaviors at the oil-water interface and its ability to disrupt asphaltene-resin aggregates. EXPERIMENTS: Several coarse-grained models of oil-water systems, with CHPEI, are constructed using dissipative particle dynamics (DPD) simulation. Following the insights gained from the simulations, a series of CHPEI-based demulsifiers are designed and synthesized. Demulsification experiments are conducted on both simulated and crude oil emulsions, with the process monitored using laser scanning confocal microscopy. Additionally, adsorption kinetics and small angle X-ray scattering are employed to reveal the inherent structural characteristics of CHPEI demulsifiers. FINDINGS: CHPEI demonstrates over 96.7 % demulsification efficiency in high acid-alkali-salt systems and maintains its performance even after multiple reuse cycles. The simulations and macroscopic experiments collectively elucidate that the effectiveness of a demulsifier is largely dependent on its molecular weight and the balance of hydrophilic and hydrophobic groups. These factors are crucial in providing sufficient interfacial active functional groups while avoiding adsorption sites for other surfactants. Collaborative efforts between DPD simulation and macroscopic measurements deepen the understanding of how demulsifiers can improve oil-water separation efficiency in emulsion treatment.

7.
Methods Mol Biol ; 2857: 45-59, 2025.
Article in English | MEDLINE | ID: mdl-39348054

ABSTRACT

Flow cytometry serves as a crucial tool in immunology, allowing for the detailed analysis of immune cell populations. γδ T cells, a subset of T cells, play pivotal roles in immune surveillance and immune aging. Assessing the phenotype and functional capabilities of γδ T cells isolated from whole blood or tissue within the context of human aging yields invaluable insights into the dynamic changes affecting immune function, tissue homeostasis, susceptibility to infections, and inflammatory responses.


Subject(s)
Aging , Flow Cytometry , Immunophenotyping , Receptors, Antigen, T-Cell, gamma-delta , Humans , Immunophenotyping/methods , Aging/immunology , Flow Cytometry/methods , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes/immunology
8.
Cell Rep ; 43(10): 114793, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39356635

ABSTRACT

Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup condensates, promoting a liquid-like state. Nsp1's presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC defects and a general decline in protein quality control that quantitatively mimics aging phenotypes. These phenotypes can be rescued by a cytosolic form of Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.

9.
Nano Lett ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356651

ABSTRACT

High-performance separation materials for oil-water emulsions are crucial to environmental protection and resource recovery; however, most existing fibrous separation materials are subject to large pore size and low porosity, resulting in limited separation performance. Herein, we create high-performance membranes consisting of spherical-beaded nanofibers and nanoarchitectured networks (nano-nets) using electrostatic spinning/netting technology, for water-in-oil emulsion separation. By manipulating the nonequilibrium stretching of jets, spherical-beaded nanofibers capable of generating a robust microelectric field are fabricated as scaffolds, on which charged droplets are induced to eject and phase separate to self-assemble nano-nets with small pores. Benefiting from 3D undulating networks with cavities originating from 2D nano-nets supported by 1D spherical-beaded nanofibers, the membranes exhibit under-oil superhydrophobicity (>152°), a striking separation performance with an efficiency of >99.2% and a flux of 5775 L m-2 h-1, together with wide pressure applicability, antifouling, and reusability. This work may open up new horizons in developing fibrous materials for separation and purification.

10.
Nano Lett ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356732

ABSTRACT

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and purification of targeted systems. Herein, oriented 1D NH2-CuBDC·H2O metal-organic frameworks (MOFs) featuring accessible CuII sites are successfully fabricated by bottom-up interfacial polymerization. The prepared MOFs, as deliberately self-assembled secondary particles, exhibit a visually detectable coordination-responsive characteristic induced by the nucleophilic substitution and competitive coordination of guest molecules. As a versatile phase-change chemosorbent, the MOFs exhibit unprecedented NH3 capture (18.83 mmol g-1 at 298 K) and bioethanol dehydration performance (enriching ethanol from 99% to 99.99% within 10 min by direct adsorption separation of liquid mixtures of ethanol and water). Furthermore, the raw materials for preparing the 1D MOFs are inexpensive and readily available, and the facile regeneration with water washing at room temperature effectively minimizes the energy consumption and cost of recycling, enabling it to be the most valuable adsorbent for the removal and separation of target substances.

11.
J Environ Manage ; 370: 122776, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39357442

ABSTRACT

With the increasing demand for effective methods to address environmental pollution, piezocatalysis has emerged as a promising approach for pollutant degradation under mechanical energy. However, the development of highly efficient piezocatalytic materials remains a challenge. This study aimed to increase the piezocatalytic activity of bismuth titanate (Bi4Ti3O12) by modifying it with zinc stannate (ZnSnO3) nanocubes. The composite catalysts were synthesized using a straightforward deposition and calcination process. The calcination process ensured the tight adhesion of ZnSnO3 nanocubes to the Bi4Ti3O12 surface, while facilitating strong interactions between ZnSnO3 and Bi4Ti3O12, which enhanced electron transfer and heterojunction structure formation. Band structure analysis indicated that Bi4Ti3O12 has higher conduction band and valence band potentials than ZnSnO3, forming a type-II heterojunction. Bi4Ti3O12 possesses a higher Fermi level than ZnSnO3, resulting in interfacial electron drift and formation of a built-in electric field, which further promotes the directional transfer and separation efficiency of charge carriers within the composite catalyst. This hypothesis was confirmed by surface photovoltage spectroscopy, piezoelectric current response, and electrochemical analysis. Consequently, the ZnSnO3/Bi4Ti3O12 composite exhibited significantly improved piezocatalytic performance in RhB degradation, achieving a degradation efficiency of 80 % within 90 min under ultrasonic vibration. The degradation rate of the optimal sample was 8.2 times that of Bi4Ti3O12 and 6.3 times that of ZnSnO3. Additionally, experiments to detect reactive species were conducted to elucidate the mechanism behind the piezocatalytic RhB degradation. Holes and hydroxyl radicals were the main reactive species. This study may offer new insights into the design of efficient piezocatalytic materials.

12.
J Mol Biol ; : 168807, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39357814

ABSTRACT

Following decades of innovation and perfecting, genetic code expansion has become a powerful tool for in vivo protein modification. Some of the major hurdles that had to be overcome include suboptimal performance of GCE-specific translational components in host systems, competing cellular processes, unspecific modification of the host proteome and limited availability of codons for reassignment. Although strategies have been developed to overcome challenges, there is critical need for further improvement. Here we discuss the current state-of-the-art in genetic code expansion technology and the issues that still need to be addressed to unleash the full potential of this method in eukaryotic cells.

13.
ACS Chem Neurosci ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39358890

ABSTRACT

Intrinsically disordered regions (IDRs) in proteins can undergo liquid-liquid phase separation (LLPS) for functional assembly, but this increases the chance of forming disease-associated amyloid fibrils. Not all amyloid fibrils form through LLPS however, and the importance of LLPS relative to other pathways in fibril formation remains unclear. We investigated this question in TDP-43, a motor neuron disease and dementia-causing protein that undergoes LLPS, using thioflavin T (ThT) fluorescence, NMR, transmission electron microscopy (TEM), and wide-angle X-ray scattering (WAXS) experiments. Using a fluorescence probe modified from ThT strategically designed for targeting protein assembly rather than ß-sheets and supported by TEM images, we propose that the biphasic ThT signals observed under LLPS-favoring conditions are due to the presence of amorphous aggregates. These aggregates represent an intermediate state that diverges from the direct pathway to ß-sheet-dominant fibrils. Under non-LLPS conditions in contrast (at low pH or at physiological conditions in a construct with key LLPS residues removed), the protein forms a hydrogel. Real-time WAXS data, ThT signals, and TEM images collectively demonstrate that the gelation process circumvents LLPS and yet still results in the formation of fibril-like structural networks. We suggest that the IDR of TDP-43 forms disease-causing amyloid fibrils regardless of the formation pathway. Our findings shed light on why both LLPS-promoting and LLPS-inhibiting mutants are found in TDP-43-related diseases.

14.
Front Neurosci ; 18: 1446912, 2024.
Article in English | MEDLINE | ID: mdl-39351392

ABSTRACT

The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.

15.
Water Res ; 267: 122492, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39353346

ABSTRACT

Microplastics have been identified as a potentially emerging threat to water environment and human health. Therefore, there is a pressing demand for effective strategies to remove microplastics from water. Hydrocyclone offers a rapid separation and low energy consumption alternative but require reduction of microparticle entrainment by short flow, which limits the effectiveness for small density differentials and ultralow concentrations separation. We proposed an enhanced mini-hydrocyclone with overflow microchannels (0.72 mm width) based on the active control of short flow in hydrocyclone for microplastic removal from water. The overflow microchannels effectively redirect the particles that would typically be entrained by the short flow, leading to higher separation efficiency. Simulation results show overflow microchannels effectively reduced short flow to 0.7 %, a reduction of up to 94 % compared to conventional hydrocyclones. The hydrocyclone with overflow microchannel demonstrated a removal efficiency exceeding 98 % for 8 µm plastic microbeads at ultralow concentrations (10 ppm), which is a 33.7 % improvement over conventional hydrocyclone. Compared with other methods (e.g., filtration, adsorption, coagulation) for microplastic removal, this work achieves rapid separation capability and long period operation, highlighting hydrocyclone as a promising approach for microplastic removal in industry-scale water treatment.

16.
Int Immunopharmacol ; 143(Pt 1): 113212, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39353387

ABSTRACT

Recent advancements in tumor immunotherapy, particularly PD-1 targeted therapy, have shown significant promise, marking major progress in tumor treatment approaches. Despite this, the development of resistance to therapy and mechanisms of immune evasion by tumors pose considerable obstacles to the broad application of immunotherapy. This necessitates a deeper exploration of complex immune signaling pathways integral to tumor immunity. This review aims to critically analyze the role of liquid-liquid phase separation (LLPS) within tumor immunity, specifically its impact on immune signaling pathways and its potential to foster the development of novel cancer therapies. LLPS, a biophysical process newly recognized for its ability to spontaneously segregate and organize biomacromolecules into liquid-like condensates through weak multivalent interactions, offers a novel perspective on the formation of signaling clusters and the functionality of immune molecules. The review delves into the micromolecular mechanisms behind the creation of signaling condensates via LLPS and reviews recent progress in adjusting signaling pathways pertinent to tumor immunity, including the T cell receptor (TCR), B cell receptor (BCR), immune checkpoints, and innate immune pathways such as the cGAS-STING pathway, stress granules, and the ADP-heptose-ALPK1 signaling axis. Furthermore, it considers the prospects of utilizing LLPS to generate groundbreaking cancer therapies capable of navigating past current treatment barriers. Through an extensive examination of LLPS's impact on tumor immunity, the review seeks to highlight novel therapeutic strategies and address the challenges and future directions in this rapidly evolving field.

17.
J Hazard Mater ; 480: 135941, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39366045

ABSTRACT

Nano-structured hydrogel with unique anti-oil fouling property exhibits big advantage in oil/water separation, but its application in complex oily wastewater (contain oils, organic matter, bacteria, etc.) cleanup is hampered by the insufficient capabilities in multi-antifouling and synergistic treatment. Herein, we constructed the amino-rich NH2-AgBiS2/PANI (polyaniline)-g-C3N4 based multi-functional hydrogel functional layer onto the polyacrylonitrile (PAN) fiber membrane via polyphenol-mediated chitosan gelation and vacuum-assisted self-assembly techniques. The unique honeycomb-like structure and super-wetting feature synergistically contributed to the powerful oil resistance and flux breakthrough of composite membrane. Such membrane achieved superior permeability (up to 3558 L-1 m-2 h-1) for various SDS-stabilized oil-in-water emulsions and remarkable synergistic treatment efficiency of multicomponent pollutant-oil-water emulsion. The rational design of hydrogel layer on membrane surface intensified the photo-response ability and multiple electron transport channels, which offered the favorable photocatalytic self-cleaning performance towards degradation of organic dyes. According to the free radical quenching and EPR experiments, the photocatalytic mechanism was proposed. In addition, the inhibition rate of E. coli could reach 100 % under illumination of 24 h. Therefore, the integration of ultra-low oil adhesion, photocatalytic self-cleaning, and antibacterial features endows membrane with exceptional multiple anti-fouling performance, exhibiting unique advantages over traditional membranes in handling complex membrane fouling issues.

18.
J Hazard Mater ; 480: 136012, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39366046

ABSTRACT

Manipulating materials of different dimensions into heterogeneous nanofiltration membranes with unique physicochemical properties and molecular sieving channels provides an effective way for accurate and fast molecular separation. Here we introduce a heterogeneous structure hybrid connection strategy to fabricate biodegradable wood-based covalent organic framework (COF) composite membranes. As a proof of concept, 3D Picea jezoensis (Siebold & Zucc.) Carrière was selected as the substrate of the membrane and in situ growth of 2D iCOF selective layers. Effective modulation of iCOF layers by 1D sulfonated polyaryletherketone (SPEEK-Na) using the "needle and thread" method. The rearrangement of the above multidimensional materials formed charge-regulated properties of laminar nano-channels and smooth hydrophilic contact area, thereby endowing specific molecular transport pathways and sieving capability for efficient dye/salt separation under ultra-low pressure of 0.5 bar. The wood-based heterostructured membranes exhibited high dye rejection (>97 %), low salt rejection (<10 %), and high permeance (172.34 L m-2 h-1 bar-1), which is superior to many reported dye/salt separation membrane materials. In addition, the system exhibited a certain degree of operational stability, good antifouling, and soil biodegradability. Overall, this work enables the design and fabrication of heterostructured separation membranes to be obtained from nature and used in nature, resulting in efficient and sustainable water purification applications.

19.
Proteins ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39366918

ABSTRACT

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

20.
J Hazard Mater ; 480: 136026, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39368361

ABSTRACT

Environmental contamination from oil spills and industrial oily wastewater poses significant ecological risks due to the persistence of harmful organic compounds. To address these challenges, magnetic composite nanospheres (CMNP@CHPEI) are systematically developed, with carboxylated Fe3O4 nanoparticles (CMNP) as the core and amphiphilic hyperbranched polyethyleneimine (CHPEI) as the decorated shell. These novel nanospheres combine the controllable size and magnetic responsiveness of "hard" magnetic nanomaterials with the structural complexity and functional diversity of "soft" hyperbranched polymers. This design allows for switching between emulsification and demulsification behaviors by regulating the size of the nanospheres and the amphiphilicity of CHPEI. Specifically, the nanospheres can form Pickering emulsions with oil droplet sizes smaller than 1 µm, maintaining stability for up to 75 days, and achieve rapid oil-water separation with demulsification efficiencies up to 99.8 %. Even after seven recycling experiments, they still retain significant interfacial activity and applicability. Interfacial characteristic experiments and molecular dynamics simulations reveal that particle size directly affects the film structures formed at oil-water interface, while the amphiphilic functional molecules determine the interaction mode of nanospheres with oil-water phases. These achievements introduce a versatile, environmentally friendly material for removing hazardous oil-based pollutants, with promising applications in oil spill remediation and industrial wastewater treatment.

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