Biophysical reviews最新文献

Overall, the school collected presentations on molecular biophysics and experimental techniques, addressed major unresolved challenges in the field, and shared an overall perspective on future directions that might help to clarify the important questions that emerged during the last decade of intensive research. To conclude, we note growing interest in AI applications for biophysical modeling, new physical experimental techniques such as cryo-microscopy, applications of modeling in pharmaceutical research, and drug design. We believe this special journal issue will be of interest to readers.

Nucleic acids are primary therapeutic targets, and understanding drug-DNA interactions is essential to the discovery of new clinical agents. In recent years, the desire to develop therapies with specific biological targets has produced new molecules that preferentially interact with complex nucleic acid sequences and structures. As such, the targeting of non-canonical nucleic acids, including DNA triplexes, G-quadruplexes, i-motifs, three-way junctions and Holliday junctions, have emerged due to their roles in gene regulation, genome stability and cellular stress responses. Characterising the interactions of these non-canonical structures with new ligands and metal complexes has led to the discovery of promising agents with therapeutic potential. Biophysical techniques including spectroscopic methods, crystallography and biomolecular assays have been critical to probing these interactions. This review describes recent advancements in the analysis of higher-order drug-DNA interactions for the rational design of targeted therapeutics.

The process of reaction-diffusion combined with advection plays a crucial role in biological systems. It establishes concentration gradients inside the cells, which in turn facilitates the regulation of signaling and metabolic activities. Theoretical descriptions of these processes make use of boundary problems linked to parabolic partial differential equations. This review focuses on the key biological characteristics that contribute to the formulation of the governing equation. The explanation of biochemical processes and transport mechanisms confirms the validity of both the terms in the equations and the established boundary conditions. In the context of real biological objects, a meticulous description of the modeled area is a fundamental requirement. Therefore, special care is taken in the formulation of algorithms that facilitate the creation of three-dimensional digital phantoms. The concept of phantom creation was illustrated through the application of 3D Voronoi diagrams. Indeed, in biological systems, fluid dynamics also play a crucial role, enabling the characterization of advection via the solution of boundary problems associated with the Navier-Stokes equation or through the application of the Darcy law in porous media. Furthermore, the convection velocity field is incorporated into the reaction-diffusion equation, and efforts are made to determine the solutions through numerical methods. The results acquired can serve to illustrate multiple biological phenomena. The capabilities of COMSOL Multiphysics software in relation to the biological aspects of reaction-diffusion are also discussed.

Integral membrane proteins are crucial molecules ubiquitous to all cell types, coordinating cell signalling and facilitating the tightly regulated transport of essential nutrients across plasma membrane. Defects in membrane proteins are associated with disease, emphasising the need to understand the structural, mechanistic and regulatory mechanisms which control integral membrane proteins. Recent technological advances in optical microscopy have allowed appropriate study of these small proteins using tools with molecular resolution which can non-invasively observe their native organisation in the plasma membrane in situ. Complimentarily, by utilising photochemical phenomena and analyses, single-molecule detail can be elucidated from conventional microscope systems. In this review, we firstly overview the methodologies used for studies of membrane proteins and then review the biophysical results gleaned from their application with an emphasis on membrane transporters. We show that single molecule studies of integral membrane proteins are beginning to unveil striking new regulatory mechanisms with wide applicability across many distinct fields of biological research.

The essential biochemical processes of blood coagulation and fibrinolysis during thrombus formation do not occur in the liquid phase but are instead restricted to specific surfaces. The classic example is phosphatidylserine-containing membranes of procoagulant platelets, which can accelerate the membrane-dependent coagulation reactions by several orders of magnitude. However, there is no clear evidence that this acceleration is the only-or even the primary-consequence of the coagulation factors' binding to the procoagulant membranes. Furthermore, other important surfaces have been identified, including fibrin (together with its numerous associated proteins) and phosphate-rich polymers such as platelet-derived polyphosphates and neutrophil extracellular traps. The distribution of these surfaces within a thrombus is non-uniform, forming complex structures at both micro- and macro-scale. This review explores possible hypotheses regarding their physiological and pathological roles: modulation of the reaction kinetics; regulation of transport processes depending on the rheological microenvironment of the thrombus; integration of coagulation, platelet activity, fibrinolysis, and tissue repair; and control of clot mechanical properties. Elucidating and validating these mechanisms may provide new insights into the development of therapeutic and diagnostic strategies.

The extensive bone defects caused by trauma or different diseases should be filled with materials that stimulate the formation of new bone tissue. The main advantages of inorganic calcium and magnesium phosphate cement materials, including injectable bone cements, are their ability to fill complex bone defects, provide appropriate mechanical properties and resorption kinetics with further new bone formation, and also provide theranostic special functional properties. These bone cements are also used in minimally invasive surgical techniques, such as vertebroplasty and kyphoplasty, as well as in oncology and dentistry. Monitoring dentistry procedures and assessing recovery during new bone formation requires observation using non-invasive methods for biovisualisation. The development of cement materials with theranostic effects could suggest a novel opportunity for treatment strategies for primary and metastatic bone tumors. This review illustrates the state of the art in modern bioimaging of bone cements based on calcium and magnesium phosphates, which refers to the use of several imaging techniques and also provides therapeutic effects, including cancer cleaning, antibacterial properties, and osteogenic differentiation.

Metabolomics has become a central approach for elucidating metabolic alterations associated with disease pathogenesis, therapeutic responses, and genetic perturbations. Among the dominant analytical platforms, nuclear magnetic resonance (NMR) spectroscopy is particularly valued for its reproducibility, quantitative accuracy, and minimal sample preparation. These strengths make NMR especially powerful for studies employing genetically engineered mouse models (GEMMs), which remain indispensable for investigating the molecular basis of human disease. This review examines key methodological aspects of NMR metabolomics, including data analysis platforms, the choice of pulse sequences, and strategies to enhance sensitivity and resolution. We summarize applications across major disease areas such as cancer, diabetes, and neurological disorders, with particular emphasis on stable isotope-resolved metabolomics, a powerful approach for dynamic pathway analysis and metabolic flux modeling in intact systems. We also highlight how NMR studies of knockout models have uncovered subtle metabolic perturbations and clarified gene-metabolism relationships. A recurring theme is the evaluation of reproducibility across GEMMs and the challenge of translating metabolic findings from mouse models to human pathophysiology. Finally, we outline current limitations and future directions for advancing the role of NMR metabolomics in preclinical and biomedical research.

Microscopy of the brain has been facing problems of contrast and thick tissue imaging. Second harmonic generation (SHG) is a non-linear effect of the light interaction with the imaged material, resulting in photon emission at half the wavelength of the absorbed light. SHG microscopy provides an unprecedented opportunity for imaging collagen and other noncentrosymmetric protein fibrils in unstained thick tissue samples and in the live brain via a regular multiphoton setup. This opens a remarkable methodological window for imaging pathological processes of high importance, including brain trauma, fibrosis, tumorigenesis, and neuroimplant-induced foreign body response. Moreover, SHG is a valuable tool for imaging astrocytes and nerve fiber microtubules. Third harmonic generation enhanced by three-photon resonance with the Soret band of hemoglobin is combined with SHG to resolve the microstructure of blood vessel walls and astrocyte-process endfeet on gliovascular interfaces. Here, we review current state-of-the-art methods in the field of brain imaging applications of SHG, including research on brain and spinal cord injury, glioma, ischemia, Alzheimer's disease, neuroimplantation, and brain meninges. We then address the method development perspective in the broader context of other tissue pathologies. Finally, we account for recent progress in artificial intelligence applications for SHG microscopy data analysis.

Neuronal imaging, or assessment of sympathetic activity of the heart, along with the study of perfusion, myocardial and coronary blood flow reserve, and contractility, is another unique facet of nuclear medicine and an integral component in unravelling and understanding the mechanisms of cardiovascular disease (CVD) development, predicting the course of the disease, preventing its complications, and choosing therapeutic tactics. Currently, nuclear cardiology methods are the only non-invasive ways of lifetime visualization of cardiac neurotransmission at the molecular level and assessment of functional integrity of sympathetic innervation circuit of the heart, violations of which may be the root cause of various CVDs. The article presents data of the literature devoted to the assessment of cardiac neuronal function in some CVDs using planar scintigraphy and single-photon emission computed tomography (SPECT) with ¹²³I-mIBG (123I-metaiodbenzylguanidine), a structural analogue of noradrenaline, which has been used in clinical practice for 45 years.