搜索结果：biomolecular

Biological macromolecules form the cornerstone of cellular architecture and function through diverse structural arrangements and dynamic interactions. Recent methodological breakthroughs have revolutionized our understanding of these complex biomolecular systems by providing unprecedented resolution of their three-dimensional organization and conformational landscapes. This review examines significant advances in both structural elucidation and functional characterization approaches that bridge the critical gap between static snapshots and dynamic behaviors exhibited within cellular environments. Non-cell-based analytical platforms have similarly evolved, offering enhanced sensitivity, multiplexing capabilities, and reduced sample requirements for interrogating molecular interactions under near-physiological conditions. The integration of experimental approaches with computational modeling has enabled the construction of comprehensive structure-function relationships that more accurately represent macromolecular behavior in native contexts. This review aims to provide a contemporary assessment of biological macromolecule research, highlighting how technological advancements continue to fill the existing bridge and integrate the prior understanding of complex biomolecular systems while addressing persistent technical challenges in their characterization, with finesse. The integration of cellular and non-cellular analytical platforms provides unprecedented precision for resolving macromolecular structures under physiologically relevant conditions.Biophysical techniques with enhanced sensitivity enable quantitative characterization of macromolecular interactions and conformational dynamics at single-molecule resolution.Advanced electrophoretic and immunochemical methods that address the challenges of stability while providing high-throughput analysis of complex macromolecular assemblies are described.Hybridized analytical technologies that combine spectroscopic and separation-based approaches deliver complementary structural and functional data from limited biological samples.Breakthroughs in structural and functional analysis are redefining biomolecular research, revealing the physical basis of cellular organization.

Micro-nano plastics (M/NPs) are pervasive environmental pollutants whose small size, persistence, and evolving surface states complicate reliable detection and remediation. As interface-dominated contaminants, their environmental behavior is largely governed by interactions at plastic-bio-nano interfaces. In this article, we review recent advances in three interconnected aspects of M/NPs research: biomolecular recognition, nano-enabled enrichment, and catalytic degradation, with particular emphasis on the central role of interfaces. Biomolecular recognition elements, including antibodies, peptides, aptamers, and molecularly imprinted materials, enable selective identification of plastics through interfacial pattern recognition. Nanomaterials such as magnetic nanoparticles, plasmonic nanostructures, metal-organic frameworks, and carbon-based materials further facilitate selective capture and signal amplification in complex matrices. Emerging degradation strategies, including engineered enzymes, enzyme-nanomaterial hybrids, nanozymes, single-atom nanozymes, and advanced oxidation processes, rely on interface-mediated adsorption, catalytic activation, and polymer transformation. Future research should therefore focus on elucidating plastic-bio-nano interfacial mechanisms and leveraging these insights to integrate molecular recognition, nano-enabled enrichment, and catalytic transformation within multifunctional platforms.

Hydrogel metamaterials with programmable microarchitectures offer a promising route for converting molecular recognition into mechanical responses. However, efficiently transducing weak biomolecular perturbations into detectable signals without relying on molecular amplification remains a fundamental challenge. Here, we report a metamaterial Buckling-Assisted Surface-acoustic-wave Enabled Sensor (mBASES), which introduces a structure-triggered physical amplification mechanism by integrating bio-crosslinked hydrogel metamaterials with a surface acoustic wave (SAW) device. Through competitive biomolecular recognition, target binding induces hydrogel swelling that is engineered to match the critical buckling threshold of the metamaterial. This instability-enabled pattern transformation acts as an intrinsic mechanical gain element, converting weak molecular perturbations into amplified acoustic responses through coupled modulation of phononic transmission and hydrogel-SAW interactions. As a result, mBASES establishes a transduction pathway that links molecular recognition, hydrogel deformation, structural amplification, and ultimately acoustic readout. The platform enables rapid, label-free detection across multiple biomolecular classes, including proteins, nucleic acids, and metabolites. Clinical validation further demonstrates femtomolar-level detection of Herpes Simplex Virus (HSV) IgG and unamplified DNA in human serum within 5-15 min using a one-step assay. By amplifying the transduction process rather than the target molecules, mBASES establishes a versatile biosensing strategy, providing a promising platform for point-of-care diagnostics.

A novel acylhydrazone Schiff base ligand, 2-fluoro-N'-[(1E,2E)-3-(2-methoxyphenyl)prop-2-en-1-ylidene]benzohydrazide (L), was synthesized and coordinated with Ni(II), Cu(II), and Zn(II) ions. The resulting complexes were characterized using TGA-DSC, FTIR/ATR, HRESIMS, 1H NMR, PXRD, elemental analysis, and complexometric titration, confirming a 1:2 metal-to-ligand stoichiometry and the formation of polycrystalline compounds. Coordination occurs via an N,O-bidentate mode through the enolic oxygen and azomethine nitrogen, forming stable five-membered chelate rings. Thermal analysis revealed high stability, with decomposition leading to the metal oxides, while PXRD indicated crystallite sizes in the 20-50 nm range. Spectroscopic DNA-binding studies via UV-Vis and fluorescence spectroscopy demonstrated moderate hypochromism (20-41%) without significant bathochromic shifts, yielding intrinsic binding constants (Kb) on the order of 104 L mol-1. Viscosity measurements and ethidium bromide displacement assays corroborated a predominantly non-intercalative groove-binding mode. Molecular docking simulations supported these experimental findings, revealing plausible minor-groove binding poses stabilized by hydrogen bonding, halogen contacts, π-anion interactions, and hydrophobic interactions, consistent with the observed DNA-binding behavior. BSA fluorescence quenching studies suggested a predominant static quenching mechanism, with binding constants in the range of 104-105 M-1, indicative of moderate, reversible ground-state complex formation with serum albumin and suggesting relevant protein-binding behavior. The combined experimental and theoretical data demonstrate that metal coordination enhances DNA affinity and modulates biomolecular interactions, particularly for the Ni(II) complex, highlighting the potential of this new acylhydrazone framework as a platform for DNA-binding coordination compounds and related studies of biomolecular interactions.

The formation of active and catalytic biomolecular condensates is critical to orchestrate intracellular biochemical reactions and cellular functions. Synthetic analogues that mimic such behaviors are typically constructed via liquid-liquid phase separation that generates liquid coacervate-based droplets, which promote reaction efficiency through molecular confinement. Such a type of confined reaction is usually achieved by partitioning and sequestrating active species such as biological enzymes or their mimics (such as metalloenzymes), which can be easily affected by encapsulation efficiency and sensitivity to the local environment. Engineering coacervate-based compartments that can display inherent catalytic functionality remains a significant challenge. Here, we report a bioinspired strategy to construct programmable peptide-based coacervates with inherent enzyme-like catalytic activity via the co-assembly of short peptides. We find that mixing the histidine-tagged short peptides with triphenylalanine-based peptides leads to the formation of a stable coacervate phase, in contrast to the rigid aggregates formed by each individual component. This cooperative assembly enables the generation of functional coacervate compartments with built-in catalytic capability. The resulting peptide coacervates exhibit selective partitioning and sequestration of hydrophobic substrates, thereby enhancing local substrate concentration and promoting catalytic hydrolysis reactions. Our results demonstrate that catalytic activity can be encoded directly into coacervate-forming building blocks through rational peptide design, providing a versatile platform for programming LLPS behavior and constructing biomimetic active materials with potential applications in synthetic biology.

Hallmarks of cancer remain incompletely addressed due to the lack of efficient treatments. In translational healthcare, aggregation-induced emission/aggregation-induced enhanced emission luminogens (AIE/AIEEgens), which display strong photoluminescence upon aggregation, have broad applications in therapeutic imaging, selective organelle tracking, and biomolecular detection. Carefully designed AIE/AIEEgens can generate intracellular reactive oxygen species (ROS), thereby activating apoptotic pathways. Here, we report a novel naphthalimide-based fluorophore functionalized with morpholine and 6-hydroxyquinoline units. DFT studies confirmed a donor-acceptor framework, with morpholine as the electron donor and the naphthalimide core as the electron acceptor. The synthesized AIEEgen morpholinonaphthalimide-6-hydroxyquinoline (M6HQ) efficiently targeted lysosomes and exhibited cytotoxicity in IMR-32 and MCF-7 cells. M6HQ enhanced lysosomal activity that instigated increased LC3-II/LC3-I expression and decreased p62 expression, indicating autophagic induction. Additionally, M6HQ elevated intracellular ROS production, leading to mitochondrial depolarization, cell cycle arrest, reduced cell migration, and apoptosis in IMR-32 and MCF-7 cells. Elevated levels of apoptotic marker proteins (cleaved caspase-3 and -9) in treated cells further supported the apoptotic cell death pathway. These findings highlight lysosome-targeted naphthalimide-based AIEE nanoaggregates as multifunctional theranostic agents that induce both autophagy and apoptosis, offering a dual-pathway strategy to overcome drug resistance and improve cancer therapy.

Precise spatiotemporal control over bioorthogonal labeling is crucial for studying biological processes in living systems. While external triggers like light offer control, methods responsive to intrinsic cellular stimuli remain scarce. Here, we report a modular, stimulus-activated bioorthogonal platform based on the iminosydnone-alkyne cycloaddition (ISAC). Inspired by the pronounced reactivity of N-unsubstituted iminosydnones, we developed a gating strategy by installing a cleavable, electron-withdrawing carbamate group at the 6-N position. This modification suppresses the cycloaddition with dibenzocyclooctyne until specific stimuli─including light, enzymes, or reactive oxygen species─remove the protecting group, rapidly restoring high reactivity. This turn-on reaction is accompanied by a fluorogenic response, enabling wash-free, stimulated-controlled fluorescent labeling of proteins and glycoproteins in live cells. Importantly, by leveraging cell-specific enzymes, we achieved selective protein labeling on target cells within cocultures, demonstrating exceptional spatial selectivity. This versatile platform provides a powerful strategy for interrogating biomolecular function with high precision in complex environments, holding great promise for studying intercellular communication and targeted delivery.

ConspectusAs molecular systems of increasing complexity come to dominate the frontiers of chemistry, biology, and materials science, the temptation grows to bypass mechanistic understanding in favor of correlations (whether empirical or learned) that capture trends without illuminating their origins. Yet, for systems governed by dense networks of noncovalent interactions, correlations without causation offer limited transferability. The deeper challenge lies in forging an understanding that is at once quantitatively rigorous and chemically intuitive: principles rooted in the physics of these interactions, capable of explaining why a system behaves as it does and of guiding its rational redesign.We believe that extracting such transferable insights from the accurate characterization of noncovalent interactions in complex systems is a central objective of modern computational chemistry. This challenge intensifies as molecular architectures grow in size and flexibility, entering a regime in which the tools of small-molecule quantum chemistry and the sampling demands of biomolecular simulations must converge. Here, we examine an especially challenging case study: harnessing London dispersion in confined asymmetric catalysis.London dispersion is among the most pervasive yet least exploited forces in asymmetric catalysis. In enzymes, precisely shaped active sites achieve extraordinary selectivity by confining substrates within pockets rich in noncovalent contacts. Confined chiral catalysts emulate this strategy: their enclosed active sites shape the conformational space of catalyst-substrate assemblies multiplying short-range contacts, enhancing a contribution whose role in stereocontrol grows with the degree of confinement.Recognizing and quantifying this role, however, demands computational strategies that match the complexity of the systems involved: large, flexible supramolecular assemblies in which competing enantiomeric pathways are separated by fractions of a kcal·mol-1. This Account shows how such strategies enable quantitative prediction of enantioselectivity and reveal London dispersion as an often overlooked yet engineerable interaction in confined asymmetric catalysis.Using imidodiphosphorimidate (IDPi) catalysts as the central case studies, we demonstrate that an accurate description of their systems requires treating key intermediates and transition states as conformational ensembles rather than single structures, where the role of the solvent adds a further layer of supramolecular complexity. With ensembles ranked to identify the arrangements that are thermally accessible under reaction conditions, electronic structure analysis enables the disentangling of the noncovalent interactions that discriminate between competing pathways.Building on the combination of quantitative accuracy and interaction-level insight, we examine recent representative case studies that illustrate how London dispersion plays a crucial role in shaping function in chiral ion-pair (CIP) catalysis. These examples reveal recognition modes reminiscent of enzymatic catalysis─from rigid lock-and-key complementarity, in which the catalyst pocket provides a fixed dispersion landscape that selectively rewards one substrate orientation, to induced-fit scenarios in which the catalytic cavity reorganizes to maximize dispersive contacts with the bound substrate, without however compromising excessively intracatalyst dispersion. We further show how dispersion involving the surrounding environment, including solvent-catalyst-substrate interactions, can introduce additional energetic bias and shift selectivity.Overall, our work emphasizes that London dispersion can be considered a structurally programmable lever for selectivity, encoded through the rational codesign of catalyst, substrate, and solvent.

Biomolecular condensates formed via liquid-liquid phase separation regulate essential cellular processes, with dysregulation implicated in neurodegeneration and cancer. Nuclear magnetic resonance (NMR) spectroscopy provides label-free, atomic-resolution insights into condensate composition, stoichiometry, physicochemical properties (e.g., viscosity and water content), and molecular interactions, overcoming the limitations of imaging and bulk techniques. This review highlights NMR's capabilities in quantifying selective partitioning of proteins, RNAs, ions, and small molecules, as well as mapping interaction hotspots in scaffold proteins, and characterizing client molecule dynamics within condensates. Finally, we point to future applications, including the study of the modulation of the protein conformational landscape by condensates, drug development targeting pathological phase transitions, and integration with advanced techniques like dynamic nuclear polarization, single-molecule microscopy, and advanced computational models for studying complex physiological systems.

Cell-derived decellularized extracellular matrix (cdECM) is being increasingly explored as a supportive biomaterial for bioengineering biomimetic 3D tumor models. The potential to represent the biomolecular diversity of the extracellular matrix in a tumor-specific mode and its production using human cell cultures renders in vitro produced matrix a particularly attractive alternative to non-human counterparts. In this review, we describe well-established and emerging strategies to modulate human ECM production in vitro, as well as showcase recent advances in decellularization and processing methodologies that have been explored across different scales and diverse biological complexities. The incorporation of cdECM into the design stages of bioengineered tumor models and its biological relevance are also discussed considering currently available alternatives to model tumor ECM. Finally, we look at the current challenges in using cdECM-based biomaterials to develop preclinically relevant models and discuss the need for innovative production approaches and methodological developments in downstream processing to widen the use of cell-derived biomaterials for tumor modelling and other applications in the tissue engineering field.

The formation of fibrous architectures via peptide self-assembly underpins numerous biological functions and biomaterial applications; however, the thermodynamic origins of multistep assembly pathways remain elusive. Here, we map the complete free-energy landscape governing the liquid-liquid phase separation (LLPS)-mediated self-assembly of an amphiphilic peptide by exploiting temperature as a tunable parameter. We discover an unexpected thermodynamic mechanism: the initial LLPS-like clustering is enthalpy-driven but limited by a positive enthalpic barrier (+121 kJ mol-1), arising from the endothermic disruption of intramolecular hydrogen bonds before interpeptide contacts can form. Subsequent nucleation and fibril growth are governed by negative entropic barriers (-56 and -39 kJ mol-1, respectively), reflecting the reorganization cost of partially ordered oligomers. The energy landscape identifies LLPS as the rate-limiting step with the highest Gibbs free-energy barrier (+26 kJ mol-1). Our findings establish a generalizable framework for decoding multistep biomolecular self-organization, with implications for designing adaptive biomaterials and understanding aberrant phase transitions in diseases.

The cis-dipyridylcalix[4]pyrrole palladium(II) complex (cis-DPC+Pd2+) forms a cage-like supramolecular structure that functions as an ion channel, as evidenced by the single ion channel current observations. A lucigenin fluorescence assay revealed that cis-DPC+Pd2+ transports chloride across membranes. The HPTS fluorescence assay revealed that cis-DPC+Pd2+ selectively transports fluoride and chloride. In a cell proliferation assay using THP-1 cells, the cell survival rate with cis-DPC+Pd2+ was lower than that with trans-DPC or trans-DPC+Pd2+. These results suggest that cis-DPC+Pd2+ causes cell death by forming supramolecular pores, allowing the passage of increased numbers of ions.

暂无摘要（点击查看详情）

To critically evaluate current evidence on the role of lipoproteins and lipid-regulating proteins in the pathophysiology of abdominal aortic aneurysm (AAA), and to explore their diagnostic, prognostic, and therapeutic implications. This joint document by the Italian Society for the Study of Atherosclerosis (SISA) and the Italian Society for Angiology and Vascular Medicine (SIAPAV) integrates mechanistic, genetic, translational, and clinical data to identify emerging therapeutic targets and future research priorities. A systematic PubMed/MEDLINE search (2013-2025) identified clinical, experimental, genetic, and omic studies investigating lipid metabolism in AAA. Evidence from epidemiological studies, genome-wide association studies, and Mendelian randomization analyses supports a causal role for LDL-cholesterol, triglyceride-rich lipoproteins, and lipoprotein(a) in AAA development and progression. HDL dysfunction, rather than reduced HDL-cholesterol levels alone, has emerged as a key contributor to vascular inflammation and extracellular matrix degradation. Lipid-regulating proteins, particularly PCSK9, ANGPTL3, and apoC-III, have been identified as potential mediators of aneurysm formation through both lipid-dependent and lipid-independent inflammatory pathways. Experimental studies suggest that targeting these pathways may attenuate aneurysm growth and rupture risk. However, despite strong biological plausibility, no dedicated randomised clinical trials have yet demonstrated that lipid-lowering therapies modify AAA progression. Lipid dysregulation is increasingly recognised as a central mechanism in aneurysmal disease. Integrated experimental, genetic, and clinical evidence supports lipid-related pathways as promising diagnostic biomarkers and therapeutic targets. Large-scale longitudinal studies and randomised trials are urgently needed to determine whether lipid-targeted interventions can alter the natural history of AAA and enable precision-based prevention and treatment strategies.

Nanopowders of magnesium aluminate spinel (MgAl2O4) were produced using a solid-state approach, involving a reaction between magnesium nitrate, aluminum nitrate, and oxalic acid. The synthesized nanomaterials' structural, morphological, and catalytic properties were examined by XRD, FTIR, TGA, SEM, EDX, BET, and TEM analyses. To evaluate their catalytic performance, the photocatalytic degradation of Rhodamine B (RhB) dye under Xenon lamp irradiation was investigated. Therefore, the combined application of photocatalysis and adsorption processes has proven to be highly effective for removing RhB from aqueous solutions. Notably, the highest removal efficiency, reaching 95% after 120 min, was obtained through photocatalytic degradation under Xe lamp irradiation.

Regulatory T cells (Tregs) maintain immune tolerance through mechanisms tightly coupled to cellular metabolism. Whereas glycolysis supports Treg migration, lipid metabolism sustains their suppressive phenotype. Here, we identify the sterol regulatory element-binding protein 1c (SREBP1c) as a central regulator of Treg immunobiology. Tregs from Srebp1c-deficient mice displayed impaired suppressive function, reduced frequencies in circulation and lymphoid tissues, and diminished expression of functional markers. These defects stemmed from intrinsic metabolic rewiring rather than systemic alterations, as both ex vivo Tregs (CD4+CD25hiFoxP3+) and in vitro-derived Tregs lacking Srebp1c were shifted toward glycolysis. Integrated transcriptomic and lipidomic analyses revealed that Srebp1c-deficient Tregs exhibited defective phospholipid remodeling, with an accumulation of lysophosphatidylcholines over phosphatidylcholines, which we attributed to enhanced cytosolic phospholipase A2 (cPLA2α) activity and disruption of the Lands cycle. Altered lipid composition impaired adenosine-mediated immunosuppression by reducing CD73 expression and extracellular adenosine generation. Accordingly, pharmacological inhibition of cPLA2α restored adenosine signaling, CD73 expression, and Treg suppressive capacity. Thus, by preserving phospholipid homeostasis, SREBP1c functions as an immunometabolic checkpoint that links lipid metabolism to adenosine-dependent Treg suppression.

暂无摘要（点击查看详情）

The ANZJP 2026 schizophrenia guideline appropriately emphasises the importance of identifying treatment-resistant schizophrenia and the timely initiation of clozapine. However, despite clear guidance on when to commence clozapine, there remains comparatively limited direction regarding the systematic assessment and management of individuals who show an inadequate response to clozapine, commonly termed clozapine-resistant schizophrenia. The absence of consistent, operationalised guidance contributes to variability in clinical practice and uncertainty regarding optimal management strategies. In this perspective article, we summarise practical, evidence-informed recommendations to assist clinicians in the assessment and management of clozapine-resistant schizophrenia. Current evidence supports the early use of clozapine once treatment-resistant schizophrenia is established, with delayed clozapine use associated with poorer outcomes. In individuals with persistent symptoms despite clozapine treatment, systematic assessment is required to exclude pseudoresistance, including non-adherence, drug interactions, altered metabolism, and subtherapeutic plasma clozapine concentrations. Therapeutic drug monitoring is therefore a core component of care. Optimisation of clozapine should prioritise individualised adjustment of plasma concentrations guided by clinical response, adverse effects, and tolerability, rather than reliance on fixed concentration thresholds alone. Where an adequate trial of optimised clozapine has failed, augmentation strategies may be considered, with preference given to interventions supported by meta-analytic findings and real-world effectiveness data, while recognising the modest and inconsistent benefits observed across studies. Augmentation trials should be time-limited, systematically evaluated and if no meaningful improvement occurs, should be discontinued rather than continued indefinitely. Despite decades of research, no augmentation strategy has demonstrated consistent efficacy in clozapine-resistant schizophrenia. Future research should prioritise adequately powered, placebo-controlled trials and standardised definitions of treatment-resistant schizophrenia and clozapine-resistant schizophrenia to enable clearer treatment algorithms and more reliable clinical pathways for this patient group.