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Transfer Learning across Material Properties Using Center-Environment Features: From Energetics to Mechanical Properties in Multicomponent Mo Alloys.

Transfer learning (TL) provides a viable approach to mitigate data scarcity in materials informatics. While conventional TL focuses on predicting identical properties across different systems, this work demonstrates a cross-property extension of TL from energy to mechanical properties via end-to-end model weight pre-training and fine-tuning: knowledge learned from predicting substitution energies is transferred to predict distinctly different mechanical properties, substantially improving computational efficiency given the typically higher cost of acquiring target-domain data. To accelerate computational alloy design, machine learning models using center-environment (CE) features were first developed to predict substitution energies of alloying elements in molybdenum (Mo)-based alloys. The Random Forest models achieved the optimal performance and transferability-R2 = 0.97, 〈MAE〉 = 0.11 eV, and 〈RMSE〉 = 0.16 eV-against the density functional theory (DFT) benchmark. The model dependency of feature selection and importance analysis was discussed. The transferability of the energy models was validated on unknown systems with new elements. Subsequently, the energy models were fine-tuned using limited mechanical property data to construct energy-to-property (E2P) TL models capable of predicting elastic properties, including bulk modulus, Young's modulus, shear modulus, and elastic constants, achieving an improved accuracy over the non-transferred ML by ∼10-30%, with its transferability verified by additional DFT calculations. This cross-property E2P transfer learning framework opens a new avenue for accelerating computational materials discovery and may be extended to other multiproperty predictions governed by similar physical principles.

center-environment feature

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30 kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50 kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays

Nuclear rupture in confined cell migration triggers nuclear actin polymerization to limit chromatin leakage.

Upon cell migration in confined space, such as during cancer metastasis, mechanical forces from the extracellular matrix act onto the nucleus leading to nuclear envelope (NE) rupture, chromatin leakage and genomic instability. Here we found that during confined migration, NE rupture triggers dynamic nuclear F-actin formation dependent on the formins DIAPH1 and DIAPH3. We show that DIAPH3 dynamically and transiently relocates to the nucleus upon NE rupture. Interfering with DIAPH1/3 or with nuclear actin polymerization resulted in nuclear instability during confined migration. Notably, nuclear formin activity or actin assembly limit NE rupture-induced chromatin leakage. Similarly, silencing of Ataxia Telangiectasia and Rad3-related protein (ATR) reduced NE rupture-triggered nuclear F-actin assembly and increased chromatin leakage. Consistent with this, ATR promotes the phosphorylation of DIAPH3 at S1072 adjacent to its autoregulatory domain to promote nuclear actin polymerization. Using atomic force microscopy, we found that nuclear actin assembly or nuclear DIAPH3 activity promotes nuclear stiffness in an ATR-dependent manner. Thus, our study identifies an ATR-formin module that regulates nuclear mechanical properties through induction of intranuclear actin scaffolding.

Formins

Reverse transcription progression and genome length regulate HIV-1 core elasticity and disassembly.

The structural and mechanical properties of the HIV-1 core are critical for successful infection, balancing stability for early replication and controlled disassembly for genome release. Recent studies have highlighted the role of core elasticity in nuclear entry, yet the molecular determinants regulating this property remain poorly understood. Here, atomic force microscopy (AFM) was used to investigate the relationship between reverse transcription progression, genome length, core elasticity, and disassembly. The results demonstrate that reverse transcription induces a gradual loss of elasticity, rendering the core increasingly brittle as DNA synthesis progresses. Cores containing shorter genomes remained highly elastic, whereas those with longer genomes exhibited increased brittleness, structural damage, and a higher degree of disassembly, after 4 hours of reverse transcription. Additionally, cores from an RNase H-deficient HIV-1 mutant retained high elasticity. These findings provide insight into the interplay between genome synthesis, core integrity, and nuclear entry, supporting a model in which reverse transcription-generated mechanical stress facilitates uncoating. Furthermore, early-stage reverse transcription preserved core elasticity, suggesting a temporal window for successful nuclear import before structural destabilization compromises infectivity.

HIV-1

An NFATC4 phospho-switch links matrix stiffness to fibroblast fate.

Fibrosis is driven by the activation of quiescent fibroblasts into contractile, matrix-secreting myofibroblasts, a transition governed jointly by biochemical signals and by the mechanical properties of the ECM. How the physical stiffness of tissue is converted into a durable transcriptional cell fate decision has remained poorly understood. In this issue of the JCI, Kadri et al. used global phosphoproteomic profiling of primary human lung fibroblasts across a defined stiffness gradient to identify phosphorylation of NFATC4 at residues S213/S217 as a mechanosensitive switch that is both necessary and sufficient for the fibroblast-to-myofibroblast transition. They validated these predictions in an independent transcriptomic dataset from patients with idiopathic pulmonary fibrosis, showing that NFATC4 expression increased with disease severity. Prior work has implicated NFATC4 activation in cardiac and hepatic fibrosis, suggesting that this single modification may serve as a convergence point for mechanical and cytokine signals across fibrotic diseases.

Humans

Matrix Mechanics Governs Mechano-Metabolic Adaptation across Cancer Grades in Bladder Spheroids.

Extracellular matrix (ECM) mechanics is pivotal regulators of tumor progression, yet how viscoelasticity and matrix architecture converge to shape metabolic and invasive adaptation remains insufficiently defined. We postulate that mechanical stimuli from the ECM induce coordinated changes in adhesive and metabolic pathways, and that the nature of this independent mechano-metabolic pathway is conserved across benign, low-invasive, and high-invasive bladder cancer phenotypes. Therefore, we engineered collagen-hyaluronan hydrogels with tunable stiffness to recapitulate soft and rigid tumor microenvironments and profiled bladder cancer spheroids representing benign, low-invasive, and highly invasive states. Integrating hydraulic force spectroscopy, rheology, and molecular phenotyping, we show that matrix stiffening differentially reprograms spheroid architecture, motility, and adhesion- and metabolism-related gene expression. Spheroid behavior emerged from the interplay between intrinsic mechanical properties, matrix rheology, and molecular adaptation. HCV29 spheroids formed rigid, compact structures, relying on cell-matrix adhesion rather than metabolic or proteolytic remodeling. HT1376 spheroids activated glycolysis (HK2) and MMP-2-dependent ECM remodeling in soft matrices, but remained largely nonmigratory, indicating decoupling of invasive priming from motility. T24 spheroids were soft, deformable, and highly migratory in compliant matrices, integrating metabolic reprogramming, adhesion remodeling (E-/N-cadherin, SDC4), and radial collagen fiber alignment to drive invasion. Notably, canonical FAK/AKT/mTOR signaling was absent across all spheroids, while pS6 ribosomal protein and ILK indicated noncanonical, SDC4/integrin-ILK-dependent mechanotransduction supporting cytoskeletal dynamics, metabolism, and ECM remodeling. Collagen organization further differed across spheroid types, with dense, radially aligned fibers in HT1376, intermediate architecture in HCV29, and loose, disorganized networks in T24, closely matching their distinct migratory behaviors and cell-ECM interactions. These findings reveal stage-specific mechanometabolic strategies in bladder cancer, demonstrating how ECM mechanics and architecture jointly guide invasion, metabolic adaptation, and local immune modulation, including the regulation of immune cell infiltration and tumor immune evasion.

Humans

Pathogenic role of serpin B3-positive neutrophils in reinforcing thrombus stiffening during ischemic stroke.

The contribution of immune cells to thrombus architecture and mechanical properties in acute ischemic stroke (AIS) remains poorly understood. Using 3-dimensional imaging and multiplex staining, we mapped immune cells in human stroke thrombi and identified neutrophils as the dominant population. Analysis of 19 thrombi confirmed their positive correlation with collagen, increased stiffness, and poorer clinical outcomes. To preserve spatial context, we developed a laser capture-based proteomic workflow and analyzed thrombus neutrophils from 34 patients with AIS stratified by 90-day outcomes, followed by validation in an independent cohort of 22 patients. Proteomic analysis revealed serpin B3 as a neutrophil-enriched protein strongly correlated with poor prognosis. In murine models of ferric chloride-induced carotid artery thrombosis and middle cerebral artery occlusion, experiments using wild-type, neutrophil-depleted, and Serpinb3a knockout mice demonstrated that neutrophil-derived serpin B3 promotes early thrombus formation, enhances collagen deposition, and contributes to progressive thrombus stiffening. Mechanistically, serpin B3 secreted by neutrophils amplifies thrombus stiffness through upregulation of transforming growth factor β1, neutrophil extracellular traps, and COL1A1. Targeted Serpinb3a knockdown delayed vascular occlusion, improved thrombolysis efficiency, and resulted in better neurological recovery. Collectively, these findings identify a neutrophil-driven mechanism underlying thrombus stiffening and establish SERPINB3 as both a prognostic biomarker and a promising therapeutic target in AIS. This project has been registered with the Chinese Clinical Trial Registration Platform (https://www.chictr.org.cn/index.html) and has successfully passed the review process (registration number: ChiCTR2300077911).

Animals

Integrated experimental and bioinformatics analysis reveals ECM-integrin and redox signaling associated with PMMA/NiO nanocomposites for craniofacial applications.

BACKGROUND: Poly(methyl methacrylate) (PMMA) is widely used in dental and craniofacial applications; however, its clinical performance is limited by poor surface wettability, moderate mechanical strength, and restricted biological activity. Integrating nanomaterial engineering with computational biology offers an opportunity to better understand biomaterial-cell interactions and support the rational design of functional biomaterials. METHODS: Nickel oxide (NiO) nanoparticles were synthesized via chemical precipitation and incorporated into PMMA to fabricate nanocomposites. Physicochemical characterization included contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Vickers hardness testing. Biocompatibility was evaluated using zebrafish embryo developmental assays. To explore biological processes potentially associated with biomaterial-cell interactions, bioinformatics analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING protein-protein interaction (PPI) network analyses were performed. RESULTS: Incorporation of NiO nanoparticles improved the surface and mechanical properties of PMMA, reducing the contact angle from 105.35° to 90.46° and increasing Vickers hardness compared with unmodified PMMA. Structural and morphological analyses confirmed successful synthesis and homogeneous nanoparticle incorporation. Zebrafish embryo studies demonstrated minimal developmental toxicity, supporting the biocompatibility of the nanocomposite. Bioinformatics analyses identified significant enrichment of pathways related to extracellular matrix organization, cell adhesion, focal adhesion, PI3K-Akt signaling, and oxidative stress regulation. Protein-protein interaction analysis revealed highly interconnected networks associated with ECM-integrin signaling and redox homeostasis, highlighting biological processes potentially associated with biomaterial-cell communication. CONCLUSIONS: PMMA/NiO nanocomposites exhibited improved physicochemical performance and favorable biocompatibility characteristics. The integration of experimental characterization with bioinformatics and network-based analyses provides a systems-level perspective on biomaterial-associated cellular processes and identifies ECM-integrin signaling and oxidative stress-related pathways as candidate biological processes for future experimental validation. These findings support the continued development of PMMA/NiO nanocomposites for oral and craniofacial biomedical applications.

Nanocomposites

RADA16 as a novel hemostatic and regenerative agent in urology: European Association of Urology endourology up-to-date overview.

PURPOSE OF REVIEW: Self-assembling peptide (SAP) hydrogels represent a novel class of synthetic biomaterials with growing relevance in surgery. Among them, the ion-complementary peptide RADA16 has gained attention as an athermal, transparent, and biocompatible hemostatic agent. While its use is increasingly reported in multiple surgical specialties, evidence specific to urology remains fragmented. This review aims to summarize the physicochemical properties, mechanisms of action, and current clinical evidence for RADA16-based hydrogels, with a particular focus on urological applications. RECENT FINDINGS: RADA16 rapidly self-assembles into a transparent, extracellular-matrix-like nanofibrillar hydrogel upon exposure to physiological fluids, providing effective local hemostasis without reliance on the coagulation cascade. Preclinical and clinical data from other surgical fields demonstrate rapid bleeding control, favorable safety, and potential regenerative effects. Emerging urological evidence suggests that RADA16 is effective in managing hemorrhagic cystitis, radiation-induced hematuria, and bleeding during prostate surgery, including robot-assisted radical prostatectomy and benign prostate surgery. Beyond hemostasis, RADA16 may support wound healing and promotion of re-epithelialization. However, the current evidence base is limited by small sample sizes, lack of comparative studies, heterogeneous methodologies, and short follow-up. SUMMARY: RADA16-based hydrogels represent a promising adjunctive hemostatic option in urology, offering technical advantages such as transparency, absence of thermal injury, minimal swelling, and applicability in confined or high-risk settings. Robust prospective, comparative, and cost-effectiveness studies are required to define its definitive role in routine urological practice.

Humans

Ageing effects on chemical, physical, mechanical, and morphological properties of clear aligners - a systematic review.

BACKGROUND: Clear aligner (CA) therapy has experienced rapid use over the past two decades to treat orthodontic malocclusions. However, evidence on CA material degradation in the oral environment remains limited and often focuses on single brands or isolated material properties. OBJECTIVES: To investigate CA ageing characteristics across different materials and brands and evaluate the chemical, physical, mechanical, and morphological changes following simulated or intraoral ageing. SEARCH METHODS: Five databases (PubMed, Web of Science, MEDLINE [Ovid], ProQuest, and Scopus) were searched to 18 March 2026, with no restrictions. ELIGIBILITY CRITERIA: Studies assessing CA properties after intraoral use or simulated ageing (thermocycling, cyclic loading, or liquid immersion) were included. DATA COLLECTION AND ANALYSIS: Study selection followed PRISMA 2020. RoB was assessed using QUIN for purely in vitro studies, JBI for cohort in vivo studies, and Cochrane RoB 2 for RCTs. Results were synthesised narratively and organised by property domain, as substantial methodological heterogeneity precluded formal meta-analysis. Where protocols were comparable, a simple pooled weighted mean was calculated and presented graphically. RESULTS: Ninety-five studies were included. RoB was low in eight studies, moderate in sixty-two, and high in twenty-five. Chemical composition remained largely stable during ageing, though some brands showed trace elemental release. Physical, mechanical, and morphological properties showed material-dependent deterioration. Pooled discolouration was greatest with coffee (weighted mean ΔE = 70.9), versus tea (ΔE = 18.4) and red wine (ΔE = 11.5), with Invisalign® consistently exceeding the clinically perceptible threshold. Force decay of 40-90% typically occurred within 48 h. Thermoplastic polyurethane (TPU)-based and directly printed aligners (DPAs) generally showed greater susceptibility than polyethylene terephthalate glycol-modified (PETG)-based aligners, though findings on hardness, roughness, and stiffness were inconsistent. CONCLUSIONS: CA materials undergo clinically relevant degradation during use, particularly in TPU-based and DPAs aligners. Clinicians may need to prioritise material-specific protocols, reinforce dietary and cleaning instructions, and consider force decay when determining aligner replacement intervals. PROSPERO number: CRD420251110248.

Humans

Bioactive macromolecules in LAB-fermented cereals: Mechanisms of formation, functional properties, and health benefits.

Cereal and pseudo-cereal based fermented food products represent a substantial segment of global diet, nutrition as well as food security. Fermentation, especially by Lactic Acid Bacteria (LAB) increases the nutritional and functional values of foods by increasing palatability, bioavailability and minimizing antinutritional factors. LAB plays a pivotal role in synthesizing bioactive peptides, vitamins, minerals and reducing anti-nutrients parallelly. This review elucidates the mechanism through which LAB revamping nutritional macromolecules, such as peptides and polysaccharides, during fermentation and their role in the development of traditional as well as modern fermented foods. Additionally, these fermented foods have been associated with several health benefits. Recent advancement in biotechnology such as genome sequencing, functional genomics, and AI-assisted bioinformatics, have significantly enhanced our understanding of the diversity of LAB, the metabolism, and adaptation mechanisms. The combination of in silico and experimental methods has enabled the development of novel food enzymes as well as highly precise fermentation processes. Together with new innovations, growing demands for quality, consistency, safety as well as health benefits point out the significance of continued research. More studies employing both conventional and modern methods are necessary to explore these food groups completely and achieve better food quality, increased nutrition, more health benefits and comprehensive socioeconomic advantages.

Bioactive macromolecules

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis

Fused Deposition Modeling (FDM) of polyether-ether-ketone (PEEK) dental implants: A systematic review of the effect of printing parameters on mechanical behaviour and surface quality.

PURPOSE: This systematic review evaluated how FDM printing parameters influence mechanical behaviour and surface characteristics of 3D-printed PEEK and identified parameter combinations linked to the most favourable mechanical performance and surface quality. MATERIALS AND METHODS: An electronic search was conducted in: MEDLINE (Ovid), PubMed, Embase, Web of Science, Scopus, and Compendex (last update: January 2025). Studies that evaluated the effect of FDM printing parameters on mechanical and surface properties of PEEK were included. Outcomes comprised compressive, tensile, and flexural strengths, elastic modulus, fracture toughness, surface hardness, roughness, and wettability. RESULTS: Of 4005 reports screened, 54 manuscripts were included. 92.6% (n = 50) of articles showed low risk-of-bias, while 7.4% (n = 4) showed medium risk-of-bias. Tensile strength was the most investigated mechanical parameter (78%), followed by elastic modulus (41%), flexural strength (30%), compressive strength (20%), and fracture toughness (6%). Surface roughness was the most evaluated surface property (30%), followed by hardness (17%) and wettability (6%). Across studies, higher printing temperatures, lower printing speed, thinner layer thickness, and maximum infill ratio in a horizontal printing orientation were associated with higher strengths, less warpage, increased accuracy, and improved surface quality. CONCLUSION: Specific combinations of FDM printing parameters can significantly improve the mechanical and surface properties of PEEK. However, it is difficult to meet all the optimal conditions simultaneously. Thus, balancing between different parameters must be considered in practical production.

Benzophenones

Tannin-bearing hydrogel adhesives with enhanced mechanical and adhesion strength in response to protein leakage.

Anastomotic leaks are among the most severe side effects following abdominal surgeries. Conventional surgical sealants and emerging hydrogel adhesives often lose mechanical and adhesion strength when exposed to leaked digestive enzymes. Here, we report a tannin-encapsulating tough hydrogel adhesive that exhibits enhanced mechanical and adhesive properties upon the encounter of leaked proteins. The hydrogel is composed of a gelatin-acrylate crosslinked network with encapsulated tannin and can adhere to a wet surface via amine-carboxyl chemistry. In the context of anastomotic leaks, tannin within the hydrogel can form a complex with proteins including the digestive enzymes, leading to increased gel stiffness and storage modulus. The enhanced mechanical strength confers improved adhesive properties on the hydrogel adhesive. Additionally, the tannin-bearing hydrogel adhesive shows excellent antibacterial properties. This adaptive and antibacterial hydrogel adhesive provides a promising sealant for gastrointestinal surgery and other applications.

Tannins

Development of Dual-Cross-Linked AlgMA/HAMA Hybrid Hydrogels for Traumatic Wound Healing.

Traumatic injuries and uncontrolled, intense bleeding caused by surgery remain among today's leading medical problems. Traumatic wounds are not only observed on the skin but also result from internal organ ruptures caused by explosions and firearms. At this point, severe hemorrhaging can lead to hypothermia, hemorrhagic shock, organ failure, and even death due to the loss of more than 40% of blood volume. Therefore, it is crucial to halt bleeding rapidly. In this study, an alginate derivative that supports platelet aggregation and a hyaluronic acid derivative that adheres to wet tissues and induces angiogenesis, thereby promoting vascularization, have been prepared. The derivatives of alginate and hyaluronic acid were subjected to free radical photopolymerization, allowing them to cross-link in the presence of visible light. The study aims to introduce a new biomaterial featuring sodium alginate and hyaluronic acid groups that demonstrates good mechanical strength, a high swelling capacity to stabilize bleeding in the environment, and effective hemostatic properties. The chemical characterization of biopolymers was analyzed using FTIR and NMR techniques. The mechanical properties, swelling behavior, and degradation profiles of visible light cross-linked hybrid hydrogels were systematically characterized. The biocompatibility of the produced hydrogels was also evaluated using MTT and scratch wound healing tests. In addition, hemolysis and blood coagulation tests were performed to investigate the hemocompatibility and hemostatic potential of visible light cross-linked hybrid hydrogels.

Journal Article

Matrix Metalloprotease 1 (Mmp1) promotes cell fate change for epithelial-to-epithelial transition during regeneration after radiation damage in Drosophila.

Ionizing radiation (IR) is used to treat cancer, but therapeutic failure occurs when surviving cancer cells change fate and regenerate tumors through acquired stem cell-like properties. While transcriptional mechanisms underlying cell fate plasticity have been characterized, the cellular processes enabling cell movement during tissue regeneration remain unclear. We reported previously that hinge cells of the Drosophila larval wing disc convert to pouch fate and translocate to help regenerate the pouch that suffers from more IR-induced apoptosis. We report here that IR increases the expression of extracellular proteins in the hinge, including secreted proteases and cell adhesion modulators. Functional validation using RNA interference revealed that secreted Matrix Metalloprotease 1 (Mmp1) and the related secreted protease homolog Scarface (Scaf) are required in hinge cells for IR-induced cell fate conversion and translocation. IR, we found, induces Mmp1 and scaf transcripts in hinge cells via cell-autonomous JNK signaling. Overexpression of Mmp1 specifically in the hinge was sufficient to elevate Mmp1 protein levels throughout the disc and induced cell fate change of both hinge and non-hinge cells but only in the context of irradiation. Confocal imaging in a time course demonstrated that cells undergoing fate conversion remain within the epithelial layer with little evidence for delamination or epithelial-mesenchymal transition (EMT). We propose that remodeling of the extracellular environment is a critical mechanism that enables cellular reorganization during tissue regeneration. Mmp enzymes are important for cancer biology because of their role in ECM remodeling, extracellular signaling, and EMT. Our findings demonstrate for the first time that Mmp1 is necessary and sufficient for one epithelial cell type to switch to another epithelial cell type after radiation damage. These results provide a mechanistic basis for radiation therapy-induced cell fate plasticity.

Animals

Cancer stemness-modulating (CSM) proteins in pan-cancer chemoresistance: regulatory roles and mechanisms.

Cancer stemness is a property of cancer cells that plays critical roles in tumorigenesis and therapeutic resistance. We previously identified and categorized, based on literature evidence, a group of fourteen cancer stemness-modulating (CSM) circular RNAs (circRNAs) in colorectal cancer (CRC), which we termed CSM-circRNAs. In the present work, we show that the proteins regulated by these CRC CSM-circRNAs, with one exception for which information is currently unavailable, are bona fide modulators of cancer stemness across a wide range of cancer types. We, therefore, designate these proteins as CSM-proteins. As chemoresistance is a major trait of cancer stemness, we further investigated the molecular mechanisms through which CSM-proteins contribute to chemoresistance. Our analysis reveals that twelve CRC CSM-proteins are implicated in chemoresistance across fourteen cancer types and resistance to ten therapeutic agents. Nine distinct chemoresistance mechanisms are identified and organized into five broader functional axes: survival, drug processing, genome maintenance, plasticity and adaptation, leading us to propose an integrated mechanistic framework for CSM-protein-mediated chemoresistance. Most CSM-proteins operate across multiple functional axes in different cancer contexts, with survival-associated mechanisms, particularly apoptosis evasion, and epithelial-mesenchymal transition-associated plasticity emerging as the predominant modes of chemoresistance. Furthermore, transcriptional regulatory CSM-proteins exhibit broader mechanistic profiles than other molecular categories, although the strength and extent of evidence vary across proteins and cancer types. Taken together, the proposed CSM-protein pan-cancer chemoresistance framework offers a biologically and therapeutically relevant regulatory network for understanding the mechanisms underlying cancer chemoresistance based predominantly on preclinical evidence. Our findings may provide a preclinical conceptual foundation for the development of combinatorial therapeutic strategies targeting cancer stemness and chemoresistance through the CSM-circRNA-CSM-protein regulatory axis.

Cancer stemness

Inactivation of Aspergillus flavus spores by dielectric barrier discharge cold plasma: Kinetics, physiological properties and proteomic analysis.

A. flavus, as a pathogen, poses a grave threat to both human and livestock health, significantly influencing agricultural production as well. This study aimed to investigate the inactivation effect and mechanism of dielectric barrier discharge cold plasma (DBD-CP) on A. flavus spores. The results exhibited that DBD-CP effectively inactivated A. flavus spores by the Weibull + Tail model. Furthermore, the physiological and proteomic analysis revealed that DBD-CP destructed cell wall and membrane integrity, causing cellular protein leakage and increasing membrane penetration of ROS generated from DBD-CP. Although intracellular ROS was excessively accumulated, the protein levels and activities of SOD and CAT were decreased, indicating that intracellular redox homeostasis was disrupted by DBD-CP. Subsequently, DBD-CP treatment induced cellular protein oxidation and changed protein structures, resulting in unstable protein structures. Meanwhile, protein synthesis and degradation in A. flavus spores were disturbed by inhibiting ribosome biogenesis, initiation process and NEDD8-mediated UPS, which did not compensate for the loss of protein caused by oxidative damage and leakage, leading to A. flavus spore inactivation. Besides, DBD-CP could attenuate A. flavus virulence by downregulating hydrolytic enzymes and CFEM-related proteins. This study provides novel insight into the inactivation mechanism of DBD-CP against A. flavus spores, which establishes a basis for the application of DBD-CP in controlling pathogenic fungi contamination in grains and crops, promoting the development of DBD-CP in food and agricultural decontamination.

Spores, Fungal