Cell Reports Physical Science最新文献

Tryptophan and its metabolites, produced by the gut microbiota, are pivotal for human physiological and mental health. Yet, quantifying these structurally similar compounds with high specificity remains a challenge, hindering point-of-care diagnostics and targeted therapeutic interventions. Leveraging the innate specificity and adaptability of biological systems, we present a biosensing approach capable of identifying specific metabolites in complex contexts with minimal cross-activity. This study introduces a generalizable strategy that combines evolutionary analysis, key ligand-binding residue identification, and mutagenesis scanning to pinpoint ligand-specific transcription factor variants. Furthermore, we uncover regulatory mechanisms within uncharacterized ligand-binding domains, whether in homodimer interfaces or monomers, through structural prediction and ligand docking. Notably, our “plug-and-play” strategy broadens the detection spectrum, enabling the exclusive biosensing of indole-3-acetic acid (an auxin), tryptamine, indole-3-pyruvic acid, and other tryptophan derivatives in engineered probiotics. This groundwork paves the way to create highly specific transcriptional biosensors for potential clinical, agricultural, and industrial use.

Designing a soft manipulator that effectively serves human applications presents significant challenges, especially in motion robustness and accuracy. The elephant trunk, with its flexibility, strong load-bearing capacity, and dexterous yet soft tip, provides an inspiring model. Inspired by the elephant trunk’s thrust-deformation mechanism under multi-muscle action, we present the design principles of a composite tendon and pneumatic hybrid-driven tapered soft manipulator (TSM). Simulation and testing show that the TSM achieves a repeatability accuracy of 0.69 $\pm$$\pm$ 0.43 mm and single-axis errors below 2 mm. With a 2-kg load, it maintains less than 37 mm of deformation in all poses. Additionally, the TSM reduces contact pressure by 35.7% through active softening. These results highlight the manipulator’s strengths in motion stability, load-bearing capacity, and safety during human contact, showcasing its potential as a flexible limb for mobile or humanoid robots.

Current antibacterial and cytokine therapies for periodontitis have demonstrated suboptimal outcomes, and it remains challenging to achieve the two effects simultaneously in a straightforward approach to drug treatment. Here, we present a bifunctional nanoplatform based on polymer vesicles (PVs) that exhibits simultaneous broad-spectrum antibacterial and excellent immunomodulatory properties. The nanoplatform consists of PVs self-assembled from an amphiphilic block copolymer polystyrene-block-polyacrylic acid (PS-b-PAA), silver nanoparticles, and interleukin-4 (IL-4), resulting in the formation of PV/Ag@IL-4. We demonstrate the favorable biocompatibility of PV/Ag@IL-4, as well as its synergistic antibacterial and osteoimmunomodulatory properties, while emphasizing the role of PV/Ag@IL-4 in rescuing the imbalance of periodontal bone homeostasis. This bifunctional nanoplatform exhibits great potential as a candidate for synergistic antibacterial-immunomodulatory therapeutics in the treatment of periodontitis. Additionally, its versatility and simplicity make it a promising platform for developing multifunctional treatments targeting various diseases.

Polymer electrolyte fuel cells are a crucial piece of approaching net zero due to their high power density, rapid refueling, and eco-friendly operation. However, stable performance and durability rely on subtle water balance. Existing water management strategies, including humidification, drainage, and cold starts, primarily depend on indirect feedback or calibration through the output voltage. The direct, real-time measurement of the overall water content inside a fuel cell remains challenging, hindering the implementation of efficient feedback water control. To address this issue, synchronous measurement of neutron imaging and electrochemical impedance spectroscopy are carried out at various water contents. Machine learning is used to establish a non-linear correlation between the two characterizations. This enables the development of a more cost-effective and attainable real-time water-content estimation technique—inferred from a universal electrochemical impedance spectroscopy tool rather than relying solely on the limited availability of neutron imaging, which will facilitate the optimization and advancement of polymer electrolyte fuel cells.

Hydrogels are commonly utilized as a three-dimensional cell culture platform. High-stiffness hydrogels promote directional cell differentiation, but they may also restrict cellular activity. Here, we report a process utilizing sacrificial templates and nanoparticles for the preparation of multiscale hydrogels with macroporous and locally enhanced stiffness properties. The macroporous hydrogels provide ample space for cells, which facilitates cell activity and proliferation. Chemical doping of the nanoparticles creates a locally stiffness-enhanced region without affecting its macroscopic mechanical properties. This regional stiffness promotes osteogenic differentiation of encapsulated adipose-derived mesenchymal stem cells (ADSCs). Importantly, the functional activity of the ADSCs increases significantly after osteogenic differentiation in hydrogels. Notably, the hydrogels efficiently activate mechanotransduction signals in the ADSCs and influence their fate. In addition, ADSC-loaded multiscale hydrogels promote bone regeneration of rat cranial defects in animal experiments. Collectively, our findings demonstrate that this technique has promising applications in the biomedical field.

Molecular de-extinction is an emerging field that identifies potentially useful molecules throughout evolution. Here, we computationally mine genomes, searching for molecules called defensins, which play a role in host immunity. Our approach leads to the discovery of six undescribed β-defensins, five of which are derived from two different extinct bird species and one from a mammalian species. These organisms included an extinct moa species (Anomalopteryx didiformis) that inhabited New Zealand and the extinct Spix’s macaw (Cyanopsitta spixii), which was endemic to Brazil, as well as the black rhino (Diceros bicornis minor). Evolutionary and structural analyses of the β-defensins are performed to further characterize these molecules. This study identifies molecules from extinct organisms, revealing defensins and opening new avenues for antibiotic discovery.

Microbial electroactivity enables microorganisms to exchange electrons with extracellular electron donors and acceptors. Initially identified in Geobacter and Shewanella, it has now become evident that microbial electroactivity is prevalent in a variety of environments, facilitating access to distant and scarce electron donors and acceptors. This phenomenon is not confined to a few select microbes but spans across the three domains of life, viz. archaea, bacteria, and eukaryotes. In this perspective, we discuss electroactivity as a unifying metabolic trait across diverse microbial taxa, including phototrophs, sulfur-oxidizing bacteria, iron-oxidizing bacteria, nitrogen fixers, and even obligate aerobes. We highlight recent findings regarding possible mechanisms for the spread of electroactivity via horizontal gene transfer. Importantly, structurally conserved mechanisms of extracellular electron transfer (EET) across different microbial groups underscore its evolutionary significance. Considering the dominance of anaerobic metabolisms on early Earth, we propose that electroactivity is an ancestral adaptation available to all extant microorganisms.

Enzymatic fuel cells (EFCs) have emerged in recent years as a promising power source for wearable and implantable electronic devices. Here, successful in vivo implantation of a glucose/O₂ EFC beyond 70 days is reported that exploits an innovative “cavity electrode” concept for biocatalyst entrapment to address lifetime and biocompatibility issues. The hollow bioanode shows long-term in vitro bioelectrocatalytic storage stability of >25 days. The hollow buckypaper-based EFC exhibits attractive maximum voltage and power outputs of 0.62 V and 0.79 mW cm⁻², respectively, and high storage stability of ∼80% after 19 days. The maximum in vivo performance outputs are 0.34 ± 0.05 V and 38.7 ± 4.7 μW. After 74 days in Sprague-Dawley rats, the hollow EFC continues to present a stable 0.59 V. Postmortem analysis confirms high-level robustness and operational performance. Autopsy findings reveal no signs of rejection and demonstrate effective biocompatibility.

Viral translocation is considered a common way for respiratory viruses to spread and contaminate the surrounding environment. Thus, the discovery of non-eluting polymers that immobilize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon contact provides an opportunity to develop new coating materials for better infection control. Here, virion-binding polymers are discovered from an existing monomer library via experimental high-throughput screening. Among them, poly([2-diethylamino] ethyl acrylate) (pDEAEA) demonstrates dual functions: binding virions strongly and its speed to inactivate adsorbed SARS-CoV-2. Computational models are built based on the experimental screening data. Polymers that are predicted to be pro-adsorption by the virtual screening are poly(1-{4-[5-(4-methoxyphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}prop-2-en-1-one) (pMPPPP), poly(1-(6-isobutyloctahydropyrrolo[3,4-d]azepin-2[1H]-yl)-2-methylprop-2-en-1-one) (piBOHPAMP), and poly(N-(3-((1-benzylpiperidin-4-yl)oxy)propyl)acrylamide) (pBPOPAm), and these are found to adsorb virions. However, due to limitations in the diversity of structures in the training set, the computational models are unable to predict the adsorption of virions for all polymer structures. Summarily, these findings indicate the utility of the methodology to identify coating polymers that effectively immobilize SARS-CoV-2, with potential practical applications (e.g., water and air filtration).