Search Results (941)

The long-term sustainability of Australian agriculture is fundamentally constrained by the capacity, condition, availability, and governance of soil resources. Australian soils are among the oldest and most weathered globally, highly heterogeneous, and often slow or effectively irreversible to recover once degraded. Traditional approaches centred on soil health, while valuable at paddock scale, are insufficient to address national-scale challenges related to spatial variability, data continuity, economic valuation, and policy integration. This paper examines soil security as a policy-relevant framework for supporting more sustainable Australian agriculture. Building on the dimensions of soil security (capacity, condition, capital, connectivity, and codification), we synthesise recent Australian case studies to show how soil security extends beyond soil health to integrate biophysical properties, digital soil infrastructure, socio-economic value, and governance mechanisms. Drawing on recent Australian case studies, this review identifies advances in digital soil mapping, national soil assessments, economic valuation of soil capital, stakeholder connectivity, and emerging policy frameworks, while also identifying persistent gaps in regulation, data standardisation, and institutional coordination. The paper argues that soil security can help operationalise 3-N agriculture—Net-Zero, Nature-Positive, and Nutrient-Balanced systems—by translating sustainability goals into spatially explicit, place-based decisions grounded in soil realities. By explicitly accounting for soil capacity limits, condition trajectories, capital value, information flows, and codified rules, soil security can support more realistic climate mitigation strategies, targeted nature-positive interventions, and durable nutrient security outcomes. We conclude that embedding soil security more explicitly within Australian agricultural research, policy, and governance would strengthen efforts to deliver productive, resilient, and socially legitimate food and fibre systems. Without soil security, sustainability frameworks may remain difficult to operationalise consistently; with soil security, they can be translated more effectively into measurable, place-based, and durable decisions. Full article

Background/Objectives: Infection from Streptococcus pneumoniae can lead to serious complications, such as meningitis and pneumonia, in children under 2 years of age, older adults, and immunocompromised populations. Conjugate vaccines against the pathogen have been licensed for the prevention of invasive pneumococcal disease. Conjugate vaccine development is an involved process demanding extensive characterization of both the polysaccharide (PS) and protein (Pr) moieties in complex structures. One powerful tool in our analytical tool kit that can shed light on various analytical attributes of conjugate vaccines, such as molecular weight and composition and conjugation efficiency, is the size-exclusion chromatography-multi-angle light scattering detector (SEC-MALS) technique. Herein, we demonstrate the applicability of the SEC-MALS approach for pneumococcal conjugate vaccine product characterization. Methods: Capsular polysaccharides for serotypes (STs) 1, 3, 5, 10 A, 18 C, 24 F, and 33 F conjugated to rCRM197 carrier protein were chosen for this study. Results: The technique was very straightforward, with a high degree of accuracy (>90% based on standards) and repeatability (<2% RSD) for conjugate molar mass measurements. In addition, leveraging the capability of SEC-MALS for compositional analysis, we were able to get detailed information on the molecular assembly and conformation of the conjugates and further tweak the conjugation process to yield conjugates of a desired molar mass. Conclusions: Thus, this study highlights the usefulness of the SEC-MALS technique for in-depth conjugate vaccine biophysical characterization, which is critical for achieving optimal product attributes, driving manufacturing consistency and vaccine potency. Full article

The eukaryotic translation initiation factor 4E (eIF4E) family plays a dual role in plants, regulating cap-dependent protein synthesis and mediating susceptibility to viruses in the family Potyviridae. In cowpea (Vigna unguiculata (L.) Walp.), an economically important legume cultivated worldwide, the structural determinants of these isoforms remain largely unexplored. This study characterizes the genomic organization, evolutionary history, and conformational dynamics of eIF4E, eIF(iso)4E, and nCBP in cowpea using a multi-omics approach. Genome mining identified three paralogous genes located on chromosomes 4, 6, and 7, showing high synteny with Phaseolus vulgaris. Phylogenetic analysis confirmed nCBP as the ancestral Class I lineage, distinct from the Class II eIF4E and eIF(iso)4E clades. Theoretical models for the isoforms were generated and subsequently validated by molecular dynamics simulations, revealing that while all isoforms preserve the canonical tertiary architecture and an electropositive cap-binding pocket, eIF(iso)4E exhibits superior structural compactness and hydrogen-bond stability. These biophysical features highlight their role as a stable anchor for viral VPg proteins. By elucidating the atomic-level landscape of these factors, we provide a robust structural framework to guide allele mining and genome-editing strategies aiming to engineer virus-resistant cowpea cultivars without compromising agronomic performance. Full article

Embryo and organ shapes emerge from the interplay between genetic programs and physical forces. In recent years, there has been a growing appreciation of the role of mechanical forces in morphogenesis. Here, we review how the integration of advanced genetic approaches with high-resolution imaging, biophysics, and modeling has begun to yield new insights into C. elegans embryonic morphogenesis. Building on past reviews in the field, we analyze dorsal intercalation, ventral enclosure, and axis extension, with a focus on how forces impinge on cellular processes and serve to coordinate morphogenesis across adjacent tissues through mechanotransduction. We also discuss how different forms of cellular rosettes contribute to ventral patterning and head morphogenesis, which had not been discussed in previous reviews. Throughout, we highlight how the reciprocal feedback mechanisms between molecular processes and mechanical forces, as well as cell material properties, shape the embryo. Full article

Bone tissue regeneration represents a complex biological process regulated by mechanical, biochemical, and cellular interactions. It remains a major challenge in regenerative medicine due to the limited self-healing capacity of large or complex bone defects. Recent advances have highlighted the pivotal role of biophysical stimuli, such as mechanical loading, electromagnetic fields, ultrasound, and photobiomodulation, in promoting osteogenic differentiation and tissue remodeling. At the same time, bioactive substances, including growth factors, peptides delivered primarily via extracellular vesicles, and biomaterial-based delivery systems, have shown a potential role in enhancing cellular responses and modulating the microenvironment to promote regeneration. This review aims to provide a comprehensive overview of the latest progress in understanding how biophysical and bioactive stimuli converge to regulate bone regeneration and to consider their synergistic approaches that integrate physical stimulation with the controlled release of bioactive molecules. These combined strategies are promising to improve tissue integration and reduce healing times and complications, representing a future research direction. Full article

Although DNA-based data storage theoretically provides an information density of 2 bits per nucleotide, biochemical constraints transform sequence design into a high-dimensional constrained combinatorial optimization problem. The high computational cost and low encoding efficiency of conventional rule-based approaches make metaheuristic methods an effective alternative. This study proposes the TC-HUR hybrid algorithm to simultaneously optimize information density and conflicting biophysical constraints, including homopolymer (HP) length, GC content, melting temperature ($T_m$), and reverse-complement (RC) similarity. The method escapes local optima using Cauchy jump-enhanced Hunger Games Search (HGS), performs high-precision exploitation via Runge–Kutta (RUN) operators, and refines constraint violations at the nucleotide level through an adaptive intensive mutation mechanism. The algorithm is evaluated on a complex dataset of 1853 nucleotides under different noise regimes. TC-HUR outperforms RUN by 2.5% and HGS by 16.7% in average fitness. While maintaining homopolymer length near the ideal threshold, it reduces reverse-complement similarity to 19.10%, ensuring high sequence diversity. Under high-noise conditions, TC-HUR achieves a normalized edit distance of 0.1290, reducing insertion–deletion (indel) errors by approximately 14%. The results demonstrate that the proposed model effectively generates biophysically synthesizable and noise-resilient DNA codes. Full article

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of cilia are poorly described. Our goal is to quantify cilia dynamics of the RSPH4A (c.921+3_921+6delAAGT (intronic)) founder variant in Puerto Rico through biophysical properties of cilia. This approach enhances longitudinal patient care by understanding treatment progress through biophysical ciliary function. Methods: We analyzed images from HSVA of six patients with PCD homozygous for the founder variant and six healthy controls (HC) (n = 12). Results: We found that ciliary length (PCD = 7.62 ± 0.95 μm, HC = 8.12 ± 1.36 μm, p = 0.204 ns), orientation vector (PCD = 7.20 ± 0.93 μm, HC = 7.25 ± 1.01 μm, p = 0.883 ns), straight angle (PCD = 1.67 ± 0.27 rad, HC = 1.76 ± 0.29 rad, p = 0.380 ns), and area (PCD = 2.35 ± 0.52 μm², HC = 2.10 ± 0.53 μm², p = 0.264 ns) did not have statistically significant differences between PCD and HC. In contrast, bending index (PCD = 1.06 ± 0.04, HC = 1.12 ± 0.09, p = 0.01), bent angle (PCD = 1.11 ± 0.30 rad, HC = 0.67 ± 0.21 rad, p < 0.0001), net angle (PCD = 0.56 ± 0.26 rad, HC = 1.09 ± 0.35 rad, p < 0.0001), amplitude (PCD = 5.77 ± 1.25 μm, HC = 7.99 ± 1.65 μm, p < 0.0001), and amplitude per second (PCD = 48.83 ± 13.23 A(s), HC = 91.66 ± 27.96 A(s), p < 0.0001) showed significant differences between both groups. Conclusions: Reduced angular excursion and amplitude in PCD demonstrate that the beating pattern of the RSPH4A founder variant is dysfunctional as compared with healthy controls. Our study provides an objective framework to understand the biophysical properties of the RSPH4A founder variant. Full article

Super-resolution microscopy has transformed biological imaging by enabling nanoscale visualization of cellular structures beyond the diffraction limit. However, its effective application in highly dense molecular environments still poses challenges. This is the case for 3D PhotoActivated Localization Microscopy (PALM) achieved through astigmatism in bacterial cells. The limited volume of a single bacterium highly increases the probability of the intensity profiles emitted by single chromophores to overlap, thus strongly decreasing the number of localizations, leading to dramatic undersampling. Dual-color 3D super-resolution in Escherichia coli is achieved through a combination of PALM with Expansion Microscopy (Ex-PALM). PALM provides high specificity through photoactivable (PA) fusion proteins and high localization precision, while ExM physically expands the specimen and separate densely packed molecules. This hybrid approach enables dual-color 3D single-molecule localization with about 3 nm spatial resolution, thus allowing one to measure distances down to the molecular scale. This is achieved by optimizing ExM protocols in bacteria to achieve a 4-fold isotropic expansion, by minimizing both chromatic aberrations and signal crosstalk, and by improving single-molecule sensitivity through highly selective inclined illumination. The method is applied to measure the spatial distribution of HisF and HisH proteins, involved in E. coli histidine biosynthesis. By tagging each protein with a photoactivable fluorescent protein, Ex-PALM reveals that after being synthetized, they co-localize in the bacterial volume with an average 3D distance of 19 nm. By combining labeling specificity with Ex-PALM, an effective method is developed for studying molecular organization in prokaryotes and in high-density samples in general, such as cell organelles or molecular condensates, with broad applications in microbiology, synthetic biology, and cellular biophysics. Full article

Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds’ effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products. Full article

Sustainable spatial development requires land-use allocation that aligns with reflects the environment’s biophysical capacity. However, rapid urbanization and agricultural expansion often result to spatial mismatches between land utilization and land capability, the reby increasing environmental degradation and disaster vulnerability. East Java Province, one of Indonesia’s most densely populated regions, has experienced significant land-use transformation driven by demographic pressure and economic development. This study aims to evaluate the environmental carrying capacity by assessing the spatial compatibility among land capability, existing land use, and the Provincial Spatial Plan (RTRWP) using a Geographic Information System (GIS)-based analytical approach. Land capability was determined based on key biophysical parameters, including slope gradient, soil texture, drainage conditions, erosion susceptibility, effective soil depth, and flood hazard. Spatial overlay analysis was employed to identify areas of conformity and mismatch between land capability and both current and planned land uses. The results indicate that only approximately 52% of the provincial area is utilised in accordance with its land capability. In comparison, the remaining 48% exhibits varying degrees of spatial mismatch. Erosion is identified as the dominant limiting factor, affecting more than 43% of the region, particularly in mountainous and hilly landscapes. Furthermore, over 60% of East Java falls within Land Capability Classes III–VII, indicating moderate to severe environmental constraints on limitations intensive land use. High levels of spatial mismatch are concentrated in the southern upland districts—such as Pacitan, Trenggalek, southern Malang, and Lumajang, which are highly susceptible to landslides, as well as in the northern lowland corridor, including the Surabaya–Gresik–Sidoarjo metropolitan region, which faces a significantly flood risk. These findings suggest that land-use practices exceeding environmental carrying capacity substantially amplify disaster risk. Therefore, integrating land capability assessment into spatial planning and zoning regulations is essential and for promoting ecosystem-based disaster risk reduction and achieving sustainable spatial development in East Java Province. Full article

Biophysical, neurophysiological, psychological and social processes along with their interactions are complex, often non-linear and inherently time-dependent. However, time series analysis of such measurements usually requires extensive data processing and is therefore potentially associated with structural biases. This exploratory secondary analysis introduces cross-recurrence quantification analysis (CRQA), which is explicitly suited to time series with complicated non-stationary properties. We illustrate and validate CRQA using a previous study that investigated the dynamic relationship between thoracolumbar fascia deformation and back extensor muscle activity in patients with low back pain. CRQA revealed significant differences in the relationships between fascia and muscles in low back pain patients compared to healthy individuals. The analysis revealed more specific aspects of fascia-muscle coupling than traditional analytical approaches, suggesting that CRQA is a useful additional tool for investigating time-dependent interactions with dynamic complex nonlinear patterns. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common condition that can cause dyspnea, pain, and biomechanical-postural alterations, especially when overlapping with Myofascial Pain Syndrome (MPS). Balneological rehabilitation medicine can help manage COPD and MPS, but it lacks homogeneity and detailed descriptions of effective therapeutic protocols. Therefore, we conducted a case series to preliminarily evaluate the clinical effects of a detailed and codified approach, called Bio-Physico-Metric Integrated Thermal Care (BPM-ITC), for COPD+MPS. Methods: 10 patients were observed while undergoing 20 sessions of BPM-ITC in 4 weeks. Patients were assessed before and after the protocol using the Medical Research Council (MRC) dyspnea scale, Numeric Pain Rating Scale (NPRS), and the Bio-Postural Questionnaire (BPQ) for bio-physical health status. Treatments included manual therapy of key myofascial trigger points combined with crenotherapy, steam inhalations, mud therapy, vascular path, and water-based motor re-education. Results: At the end of the protocol, clinically relevant improvements were observed in almost all parameters considered in single observed cases; overall statistical analysis of the data highlighted significant positive effects in concomitance with the BPM-ITC protocol. Conclusions: The BPM-ITC protocol was followed by significant clinical improvements in the observed cases, suggesting its potential as a complementary approach for COPD+MPS. Further studies on this topic are recommended. Full article

Extracellular vesicles (EVs), particularly exosomes, have emerged as critical mediators of intercellular communication, yet the metabolite fraction of their cargo remains substantially underexplored relative to proteins and nucleic acids. This review synthesizes current knowledge on the exosomal metabolome as a functionally distinct intercellular signaling system with unique biophysical properties. We review the mechanisms proposed to govern metabolite encapsulation into exosomes, encompassing membrane transporter involvement, lipid raft partitioning, and binding to luminal proteins, and discuss the unresolved question of whether metabolite loading is selective or stochastic. Critically, we present a quantitative framework evaluating whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. We also address methodological considerations including contamination artifacts and isolation-method biases that complicate interpretation of EV metabolomics data. Exosomal metabolites are reviewed across four functional categories: energy substrates (ATP, lactate, amino acids), signaling molecules (TCA cycle intermediates, eicosanoids, nucleotides), redox cofactors and antioxidants (NADH, glutathione), and oncometabolites. For each category, available evidence is critically appraised, distinguishing metabolites with direct mass spectrometric detection from those whose roles are inferred from parent-cell biology. The review examines the roles of exosomal metabolites in tumor-stroma metabolic symbiosis, immunometabolic regulation, inter-organ crosstalk in metabolic diseases including type 2 diabetes and non-alcoholic fatty liver disease, cancer metastasis, viral infections, and immune evasion. A quantitative framework is discussed to evaluate whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. Technical challenges in exosomal metabolomics are reviewed, including the impact of isolation method on data quality, contamination artifacts, and current standardization gaps. Therapeutic implications of exosomal metabolite signaling are discussed, encompassing metabolite-loaded exosomes as therapeutic vehicles and exosomal metabolite loading as a pharmacological target. Integration of single-vesicle technologies with systems biology approaches is highlighted as a promising direction for advancing this field toward precision medicine applications in oncological and metabolic disorders. Full article

The maturation of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) remains a major translational bottleneck in regenerative cardiac medicine, as current differentiation platforms yield electrophysiologically and metabolically immature phenotypes. This review explores emerging strategies to engineer “smart” biomaterial interfaces that actively instruct iPSC-CM maturation through synergistic biophysical and metabolic reprogramming. By integrating nanotopographical patterning, mechanoelectric coupling, and tunable substrate stiffness with metabolic interventions such as mitochondrial substrate optimization and fatty acid oxidation induction, the literature reveals consistent links between cell–matrix crosstalk, sarcomeric organization, calcium handling, and oxidative metabolism. Recent advances in bioactive scaffolds and extracellular vesicle (EV)-functionalized hydrogels are highlighted as platforms capable of approximating key features of the myocardium’s native electromechanical and bioenergetic environment. Across two- and three-dimensional culture systems, this review identifies recurring maturation patterns, persistent gaps in metric standardization and long-term phenotype stability, and ongoing limitations related to scalability and translational implementation. Collectively, the findings synthesized here indicate that convergence between biomaterial engineering and metabolic programming represents a critical design principle for advancing iPSC-CMs toward functionally mature, clinically relevant phenotypes. This integrated approach enhances the fidelity of iPSC-CMs for disease modeling, drug screening, and regenerative cardiac therapies. Full article

Antibody–drug conjugates (ADCs) comprise a monoclonal antibody covalently bound to a cytotoxic payload by a linker. ADCs minimize off-target effects on healthy tissues, leveraging the specificity of monoclonal antibodies to deliver cytotoxic drugs to the intended tumor site. ADCs can be prone to poor behavior, including aggregation and misfolding, leading to poor efficacy, impaired pharmacokinetics, and immunogenicity. It is advantageous to understand the developability and potential liabilities of a protein candidate prior to costly in vivo studies or clinical trials. This review summarizes biophysical and structural techniques used to characterize ADCs and introduces emerging techniques aimed at accurately assessing the developability of protein candidates. Stability is commonly assayed using techniques like differential scanning calorimetry (DSC), differential scanning fluorimetry (DSF), or spectroscopic probes such as circular dichroism and intrinsic fluorescence. Drug-to-antibody ratio (DAR) is a critical parameter that can be measured using absorbance spectroscopy or chromatographic analysis. Aggregation and self-association can be probed using scattering techniques such as dynamic light scattering (DLS), static light scattering (SLS), and size exclusion chromatography–multi-angle light scattering (SEC-MALS), as well as more specialized approaches such as fluorescence correlation spectroscopy (FCS) and analytical ultracentrifugation (AUC). Mass spectrometry (MS) provides extremely valuable insight into stability, covalent modifications, and, through approaches like hydrogen–deuterium exchange (HDX-MS), structural dynamics of ADCs. Looking forward, the use of biophysical assays in ex vivo matrices and strategic use of artificial intelligence/machine learning (AI/ML) approaches are likely to advance the efficient and rapid development of ADCs and other next-generation protein therapeutics. Full article