Polysaccharide-Based Composite Hydrogel with Hierarchical Microstructure for Enhanced Vascularization and Skull Regeneration.

Critical-size skull defects caused by trauma, infection, and tumor resection raise great demands for efficient bone substitutes. Herein, a hybrid cross-linked hierarchical microporous hydrogel scaffold (PHCLS) was successfully assembled by a multistep procedure, which involved (i) the preparation of poly(lactic-co-glycolic)/nanohydroxyapatite (PLGA-HAP) porous microspheres, (ii) embedding the spheres in a solution of dopamine-modified hyaluronic acid and collagen I (Col I) and cross-linking via dopamine polyphenols binding to (i) Col I amino groups (via Michael addition) and (ii) PLGA-HAP (via calcium ion chelation). The introduction of PLGA-HAP not only improved the diversity of pore size and pore communication inside the matrix but also greatly enhanced the compressive strength (5.24-fold, 77.5 kPa) and degradation properties to construct a more stable mechanical structure. In particular, the PHCLS (200 mg, nHAP) promoted the proliferation, infiltration, and angiogenic differentiation of bone marrow mesenchymal stem cells in vitro, as well as significant ectopic angiogenesis and mineralization with a storage modulus enhancement of 2.5-fold after 30 days. Meanwhile, the appropriate matrix microenvironment initiated angiogenesis and early osteogenesis by accelerating endogenous stem cell recruitment in situ. Together, the PHCLS allowed substantial skull reconstruction in the rabbit cranial defect model, achieving 85.2% breaking load strength and 84.5% bone volume fractions in comparison to the natural cranium, 12 weeks after implantation. Overall, this study reveals that the hierarchical microporous hydrogel scaffold provides a promising strategy for skull defect treatment.

Electrospun Hyaluronan Nanofiber Membrane Immobilizing Aromatic Doxorubicin as Therapeutic and Regenerative Biomaterial.

Lesioned tissue requires synchronous control of disease and regeneration progression after surgery. It is necessary to develop therapeutic and regenerative scaffolds. Here, hyaluronic acid (HA) was esterified with benzyl groups to prepare hyaluronic acid derivative (HA-Bn) nanofibers via electrospinning. Electrospun membranes with average fiber diameters of 407.64 ± 124.8 nm (H400), 642.3 ± 228.76 nm (H600), and 841.09 ± 236.86 nm (H800) were obtained by adjusting the spinning parameters. These fibrous membranes had good biocompatibility, among which the H400 group could promote the proliferation and spread of L929 cells. Using the postoperative treatment of malignant skin melanoma as an example, the anticancer drug doxorubicin (DOX) was encapsulated in nanofibers via hybrid electrospinning. The UV spectroscopy of DOX-loaded nanofibers (HA-DOX) revealed that DOX was successfully encapsulated, and there was a π-π interaction between aromatic DOX and HA-Bn. The drug release profile confirmed the sustained release of about 90%, achieved within 7 days. In vitro cell experiments proved that the HA-DOX nanofiber had a considerable inhibitory effect on B16F10 cells. Therefore, the HA-Bn electrospun membrane could facilitate the potential regeneration of injured skin tissues and be incorporated with drugs to achieve therapeutic effects, offering a powerful approach to developing therapeutic and regenerative biomaterial.

Fe3O4@polydopamine nanoparticle-loaded human umbilical cord mesenchymal stem cells improve the cognitive function in Alzheimer's disease mice by promoting hippocampal neurogenesis.

One of the most promising treatments for neurodegenerative diseases is the stem cell therapy; however, there are still some limitations in the treatment of Alzheimer's disease. In this study, superparamagnetic nanoparticles composed of magnetic Fe3O4 and polydopamine shells were used to label human umbilical cord mesenchymal stem cells (hUC-MSCs) in order to increase the targeting of hUC-MSCs. Our data suggested that Fe3O4@PDA labeling increase the efficiency of hUC-MSCs entering the brain. Moreover, the water maze test showed that compared with hUC-MSCs only, Fe3O4@PDA-labeled hUC-MSCs improved the cognitive ability of APP/PS1 transgenic mice more significantly. Other experimental data showed that the expression of essential proteins in the hippocampus, such as Aß, synaptophysin, brain-derived neurotrophic factor, are affected by Fe3O4@PDA coated-hUC-MSCs. The regulation of Fe3O4@PDA coated-hUC-MSCs could improve the memory and cognitive ability of AD mice by excessive generation of neuroprotective factors, which might be considered a viable therapy to treat AD.

Copper-Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T-Cell Infiltration.

Insufficient T-cell infiltration seriously hinders the efficacy of tumor immunotherapy. Induction of immunogenic cell death (ICD) is a potentially feasible approach to increase T-cell infiltration. Since ionizing radiation can only induce low-level ICD, this study constructs Cu-based nanoscale coordination polymers (Cu-NCPs) with mixed-valence (Cu+ /Cu2+ ), which can simultaneously and independently induce the generation of Cu+ -triggered hydroxyl radicals and Cu2+ -triggered GSH elimination, to synergize with radiation therapy for potent ICD induction. Markedly, this synergetic therapy remarkably enhances dendritic cell maturation and promotes antitumor CD8+ T-cell infiltration, thereby potentiating the development of checkpoint blockade immunotherapies against primary and metastatic tumors.

Dynamical Water Ingress and Dissolution at the Amorphous-Crystalline Cellulose Interface.

The use of cellulose has considerable promise in a wide range of industrial applications but is hampered by degradation in mechanical properties due to ambient moisture uptake. Existing models of equilibrium moisture content can predict the impact of these effects, but at present, the dynamical, atomic-scale picture of water ingress into cellulose is lacking. The present work reports nonequilibrium molecular simulations of the interface between cellulose and water aimed at capturing the initial stages of two simultaneous dynamical processes, water ingress into cellulose and cellulose dissolution into water. These simulations demonstrate that the process depends on the temperature and chain length in the amorphous region, where high temperatures can induce more mass exchange and short chains can easily detach from amorphous cellulose. A cooperative mechanism that involves both chemical and physical aspects, namely, hydrogen bonding and chain intertwining, respectively, is proposed to interpret the incipient dual ingress/dissolution process. Outcomes of this work will provide a foundation for cellulose functionalization strategies to impede moisture uptake and preserve the mechanical properties of nanocellulose in applications.

Compound pesticide controlled release system based on the mixture of poly(butylene succinate) and PLA.

Controlled release system has been widely developed and utilised in agriculture to optimise efficacy and minimise environmental pollution. Here, the azoxystrobin and difenoconazole compound pesticide microsphere was constructed by the solvent evaporation method. Blending poly (butylene succinate) (PBS) and poly (lactic acid) (PLA) as shells, in order to increase its entrapment efficiency and match the goal of complex synergism. The resulting microsphere processes high entrapment efficiency with a mean diameter of 7.2 µm. Acute toxicity suggested microsphere on zebrafish was moderate toxicity. Comparative studies revealed that the microsphere had a longer period of sustained release than difenoconazole-azoxystrobin (5:8) 32.5% w/v suspension concentrate (SC). In addition, the concentration ratio of active ingredients closed to the optimum compound stoichiometry, which can achieve the objective of improving the efficacy of the pesticides. These results demonstrated that such a compound pesticide microsphere delivery system may be a considerable potential for further exploration.

Tunable AICPL of (S)-Binaphthyl-Based Three-Component Polymers via FRET Mechanism.

Five three-component chiral polymers incorporating (S)-1,1'-binaphthyl, tetraphenylethene (TPE) and fluorene moieties are designed and synthesized by Pd-catalyzed Sonogashira reaction. All these polymers show obvious aggregation induced emission enhancement response behavior in the fluorescence emission region of 460-480 nm. Interestingly, three of them show aggregation-induced circularly polarized luminescence (AICPL) signals in tetrahydrofuran-H2 O mixtures. Most importantly, these AICPL signals can be tuned by changing the molar ratios of TPE and fluorene components through fluorescence resonance energy transfer and give the highest glum = ±4.0 × 10-3 . This work provides a novel strategy for developing AICPL-enhanced materials.

An in situ generated achiral Cu(II)-containing polymer complex sensor for enantioselective recognition induced from L-/D-histidine enantiomers.

A novel achiral polymer P-1 is synthesized by the polymerization of (2,5-bis(octyloxy)-1,4-phenylene)diboronic acid (M-1) with pyridine-2,6-diylbis(methanylylidene)bis(4-iodoaniline) (M-2) via Pd-catalyzed Suzuki coupling reaction. The tridentate ligand in the main chain backbone can further coordinate with Cu(2+) to afford the corresponding achiral copper-containing polymer complex P-2, which selectively responds to L-/D-histidine with significant fluorescence enhancement over other amino acids. Interestingly, P-2 exhibits obvious CD response toward L- or D-histidine compared with its model compound MC, indicating that this kind Cu(II)-containing polymer complex sensor can be used as an effective chemosensor for enantioselective recognition of histidine enantiomers by means of CD spectroscopy.

Metal nanoparticle hybrid hydrogels: the state-of-the-art of combining hard and soft materials to promote wound healing.

Wounds represent a grave affliction that profoundly impacts human well-being. Establishing barriers, preventing infections, and providing a conducive microenvironment constitute the crux of wound therapy. Hydrogel, a polymer with an intricate three-dimensional lattice, serves as a potent tool in erecting physical barriers and nurturing an environment conducive to wound healing. This enables effective control over exudation, hemostasis, accelerated wound closure, and diminished scar formation. As a result, hydrogels have gained extensive traction in the realm of wound treatment. Metallic nanoparticle carriers, characterized by their multifaceted responses encompassing acoustics, optics, and electronics, have demonstrated efficacy in wound management. Nevertheless, these carriers encounter challenges associated with swift clearance and nonuniform effectiveness. The hybridization of metallic nanoparticle carriers with hydrogels overcomes the shortcomings inherent in metallic nanoparticle-based wound therapy. This amalgamation not only addresses the limitations but also augments the mechanical robustness of hydrogels. It confers upon them attributes such as environmental responsiveness and multifunctionality, thereby synergizing strengths and compensating for weaknesses. This integration culminates in the precise and intelligent management of wounds. This review encapsulates the structural classifications, design strategies, therapeutic applications, and underlying mechanisms of metal nanoparticle hybrid hydrogels in the context of acute and chronic wound treatment. The discourse delves into the generation of novel or enhanced attributes arising from hybridization and how the current paradigm of wound therapy leverages these attributes. Amidst this continually evolving frontier, the potential of metal nanoparticle hybrid hydrogels to revolutionize wound treatment is underscored.

Injectable Temperature-Sensitive Hydrogel Loaded with IL-36Ra for the Relief of Osteoarthritis.

Osteoarthritis (OA) is an inflammatory disease accompanied by synovial joint inflammation, and IL-36 plays an important role in this process. Local application of IL-36 receptor antagonist (IL-36Ra) can effectively control the inflammatory response, thereby protecting cartilage and slowing down the development of OA. However, its application is limited by the fact that it is rapidly metabolized locally. We designed and prepared a temperature-sensitive poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel (IL-36Ra@Gel) system carrying IL-36Ra and evaluated its basic physicochemical characteristics. The drug release curve of IL-36Ra@Gel indicated that this system could slowly release the drug over a longer period. Furthermore, degradation experiments showed that it could be largely degraded from the body within 1 month. The biocompatibility-related results showed that it had no significant effect on cell proliferation compared to the control group. In addition, the expression of MMP-13 and ADAMTS-5 was lower in IL-36Ra@Gel-treated chondrocytes than in the control group, and the opposite results appeared in aggrecan and collagen X. After 8 weeks of treatment with IL-36Ra@Gel by joint cavity injection, HE and Safranin O/Fast green staining showed that the degree of cartilage tissue destruction in the IL-36Ra@Gel-treated group was less than those in other groups. Meanwhile, the joints of mice in the IL-36Ra@Gel group had the most intact cartilage surface, the smallest thickness of cartilage erosion, and the lowest OARSI and Mankins score among all groups. Consequently, the combination of IL-36Ra and PLGA-PLEG-PLGA temperature-sensitive hydrogels can greatly improve the therapeutic effect and prolong the drug duration time, thus effectively delaying the progression of degenerative changes in OA, providing a new feasible nonsurgical treatment for OA.

Disrupted microbiota-barrier-immune interaction in phthalates-mediated barrier defect in the duodenum.

As one of the most used phthalates, Di (2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant. Extremely persistent plastic can enter the food chain of animals through the aquatic environment, affect metabolic pathways and cause damage to the digestive system. But the molecular mechanism of its toxic effects on the duodenum in birds has not been elucidated. To investigate the toxicity of phthalates in the duodenum, quails were gavaged with 250, 500, and 750 mg/kg doses of DEHP for 45 days, and water and oil control groups were retained. This study revealed that subchronic exposure to DEHP could lead to duodenal barrier defect in quail. The damage to duodenum was reflected in a reduction in V/C and tight junction proteins. Moreover, DEHP also led to a breakdown of antimicrobial defenses through the flora derangement, which acted as a biological barrier. The massive presence of Lipopolysaccharide (LPS) led to the activation of TLR4 receptors. In addition, DEHP activated oxidative stress, which synergized the inflammatory response induced by the TLR4-NFκB pathway, and further promoted duodenum damage. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction.

Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress.

Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.

A novel method based on membrane distillation for treating acid mine drainage: Recovery of water and utilization of iron.

Rapid and highly efficient treatment of acid mine drainage (AMD) is still challenging due to the low pH and high metal concentrations in it. This research focuses on a novel treatment method of AMD using direct contact membrane distillation (DCMD) and photocatalysis to recover water and utilize iron. In the DCMD process without pretreatment, the flux decreased by 93.38%. If pretreated by adding sodium oxalate, scale formation potential was effectively mitigated due to the removal of calcium and complexing of iron. For the treatment of the pretreated AMD (PAMD), 60% of water was recovered in the DCMD process with the flux decrease of 22%. The concentrate obtained from the DCMD process demonstrated high photocatalytic activity in the methylene blue (MB) degradation in an aqueous solution. In addition, the Fe (III)-oxalate complexes in the concentrate were reduced to insoluble Fe (II)-oxalate with visible light irradiation, which could be separated by sedimentation and used as a Fenton catalyst. Hence, this novel method exhibits great advantages on effectively inhibiting DCMD membrane fouling during AMD treatment, producing high-quality distillate with low conductivity, and realizing near zero-discharge of AMD.

Solubilized Cartilage ECM Facilitates the Recruitment and Chondrogenesis of Endogenous BMSCs in Collagen Scaffolds for Enhancing Microfracture Treatment.

Articular cartilage has very poor intrinsic healing ability and its repair remains a significant clinical challenge. To promote neocartilage regeneration, we fabricated two collagen (Col) scaffolds functionalized with a porcine decellularized extracellular matrix (dECM) in the forms of particle and solution named pE-Col and sE-Col, respectively. Their differences were systematically compared, including the biochemical compositions, scaffold properties, cell-material interactions, and in situ cartilage regeneration. While it is demonstrated that both forms of dECM could enhance the cell recruitment, proliferation, and chondrogenesis of bone marrow stem cells (BMSCs) in vitro, better performance was seen in the sE-Col group, which could quickly provide a more favorable chondrogenic microenvironment for endogenous BMSCs. The superiority of sE-Col was also proved by our in vivo study, which showed that the sE-Col scaffold achieved better structural hyaline-like neocartilage formation and subchondral bone repair compared to the pE-Col scaffold, according to the gross morphology, biological assessment, and micro-CT imaging analysis. Together, this study suggests that the sE-Col scaffold holds great potential in developing the one-step microfracture-based strategy for cartilage repair and also reminds us that despite dECM being a promising biomaterial in tissue engineering, the optimization of the proper processing methodology would be a crucial consideration in the future design of dECM-based scaffolds in articular cartilage regeneration.

Role of Platelet-Rich Plasma in Spinal Fusion Surgery: Systematic Review and Meta-Analysis.

BACKGROUND: Platelet-rich plasma (PRP) has been used very successfully in enhancing bone fusion in animal experiments. Also, the efficaciousness of PRP in other specialties of medicine such as dentistry, dermatology ophthalmology, and sports medicine is well documented. But the use of PRP to augment bone fusion after spinal surgery in humans is still controversial. We conducted a meta-analysis to determine the role of PRP in enhancing spinal fusion by fastening the rate of new bone formation and decreasing pain after spinal surgery in humans. METHODS: We searched PubMed, EMBASE, and the Cochrane Library studies that compared PRP versus control in enhancing spinal fusion after deformity correction. RESULTS: Five retrospective studies with 253 participants and nine prospective cohort studies with 460 participants were identified. The bone fusion rate was excellent for studies that used a high platelet concentration in PRP relative to control (odds ratio (OR) = 4.35, 95% confidence interval (CI) (2.13, 8.83), and P < 0.05) while bone fusion was poor to studies that used a low concentrate of platelet in PRP relative to control. The rate of new bone formation was high in the PRP group compared to the control group with the mean difference in Hounsfield unit (HU) 144.91 (95% CI (80.63, 209.18), P < 0.05). Time to bone fusion was short in the PRP group during the first six months of surgery relative to the control group with a mean difference of -2.03 (95% CI (-2.35, -1.7); P < 0.05). No difference was found in pain reduction by visual analog score (VAS) between the PRP group and control. CONCLUSION: PRP facilitates new bone formation and bone fusion with a minimum concentration of the growth factor 5 times that of the peripheral blood. PRP stimulatory effects are not continuous and are very effective within six months of implantation.

Microstructures, mechanical properties, and degradation behaviors of heat-treated Mg-Sr alloys as potential biodegradable implant materials.

In previous studies, Mg-Sr alloys exhibited great biocompatibility with regard to test animals, and enhanced peri-implant bone formation. The objective of the present study was to investigate the effects of heat treatments on the mechanical and corrosion properties of Mg-Sr alloys. Various heat-treated Mg-xSr (x = 0.5, 1, and 2wt%, nominal composition) alloys were prepared using homogenization and aging treatments. Mechanical tests were performed at room temperature on the as-cast, homogenized, and peak-aged alloys. As the Sr content increased, the volume fraction of Mg17Sr2 phases within the as-cast alloys increased; in addition, the mechanical strength of the alloys initially increased and subsequently decreased, while the ductility decreased. Following the homogenization treatment, the mechanical strength of the alloys decreased, and the ductility increased. Nano-sized Mg17Sr2 phases were re-precipitated during the aging treatment. The age-hardening response at 160°C was enhanced as the Sr content increased. Following the aging treatment, there was an increase in the mechanical strength of the alloys; however, there was a slight reduction in the ductility. Immersion tests were conducted at 37°C for 360h, using Hank's buffered salt solution (HBSS), to study the degradation behavior of the alloys. As the Sr content of the Mg-Sr alloys increased, the corrosion rate (CR) increased owing to the galvanic effect. The homogenization treatment consequently reduced the CR dramatically, and the aging treatment had a slight effect on the CR. The peak-aged Mg-1Sr (wt%) alloy exhibited the best combination of properties. The tensile yield strength (TYS), ultimate tensile strength (UTS), elongation, compressive yield strength (CYS), ultimate compressive strength (UCS), compressibility, and CR of the as-cast Mg-1Sr (wt%) alloy were 56.0MPa, 92.67MPa, 1.27%, 171.4MPa, 243.6MPa, 22.3%, and 1.76mm/year, respectively. The respective results obtained for the peak-aged Mg-1Sr (wt%) alloys were 69.7MPa, 135.6MPa, 3.22%, 183.1MPa, 273.6MPa, 27.6%, and 1.33mm/year. Following immersion in HBSS, the primary corrosion products of the peak-aged Mg-1Sr (wt%) alloy were Mg(OH)2, MgO, MgCO3, Mg3(PO4)2, MgHPO4, and Mg(H2PO4)2, which enhanced the corrosion resistance by forming a composite corrosion film.

[Molluscicidal effect of plastic film mulch covering method].

OBJECTIVE: To evaluate the molluscicidal effect of the plastic film mulch covering method. METHODS: In the barren land with a lot of Oncomelania hupensis snails, 3 experimental groups were set up, in which respectively using 3 different methods: a simple plastic film mulch covering method, film assisted with ammonium bicarbonate, and film assisted with amine molluscicide. In the canals, two experimental groups were set up, in which respectively using 2 different methods: simple plastic film mulch covering method and film assisted with ammonium bicarbonate. In above-mentioned areas, obstacles were cleared artificially. In each experiment group, 4 observation spots were set up, and 100 living snails were pot in each spot, and then, the plastic film mulch was evenly covered. The status of the snails was observed 3, 7, 15 and 30 days after the intervention. RESULTS: In the barren land, the snail death rates of the simple plastic film group were 20.77% and 96.92% 15 days and 30 days after the intervention, respectively. The snail death rate of the film assisted with amine molluscicide group was 80.46% 3 days after the intervention. In all the experiment groups, the snail death rates were from 96.92 to 100% 30 days after the intervention. CONCLUSION: The plastic film mulch covering method has a great molluscicide effect in the hill subtype and water network type of schistosomiasis epidemic areas.

A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands.

The targeted delivery of nanoparticles to solid tumors is one of the most important and challenging problems in cancer nanomedicine, but the detailed delivery mechanisms and design principles are still not well understood. Here we report quantitative tumor uptake studies for a class of elongated gold nanocrystals (called nanorods) that are covalently conjugated to tumor-targeting peptides. A major advantage in using gold as a "tracer" is that the accumulated gold in tumors and other organs can be quantitatively determined by elemental mass spectrometry (gold is not a natural element found in animals). Thus, colloidal gold nanorods are stabilized with a layer of polyethylene glycols (PEGs) and are conjugated to three different ligands: (i) a single-chain variable fragment (ScFv) peptide that recognizes the epidermal growth factor receptor (EGFR); (ii) an amino terminal fragment (ATF) peptide that recognizes the urokinase plasminogen activator receptor (uPAR); and (iii) a cyclic RGD peptide that recognizes the a(v)ß(3) integrin receptor. Quantitative pharmacokinetic and biodistribution data show that these targeting ligands only marginally improve the total gold accumulation in xenograft tumor models in comparison with nontargeted controls, but their use could greatly alter the intracellular and extracellular nanoparticle distributions. When the gold nanorods are administered via intravenous injection, we also find that active molecular targeting of the tumor microenvironments (e.g., fibroblasts, macrophages, and vasculatures) does not significantly influence the tumor nanoparticle uptake. These results suggest that for photothermal cancer therapy, the preferred route of gold nanorod administration is intratumoral injection instead of intravenous injection.

Lamprey parasitism of sharks and teleosts: high capacity urea excretion in an extant vertebrate relic.

We observed 10 sea lampreys (Petromyzon marinus) parasitizing basking sharks (Cetorhinus maximus), the world's second largest fish, in the Bay of Fundy. Due to the high concentrations of urea in the blood and tissues of ureosmotic elasmobranchs, we hypothesized that sea lampreys would have mechanisms to eliminate co-ingested urea while feeding on basking sharks. Post-removal urea excretion rates (J(Urea)) in two lampreys, removed from separate sharks by divers, were initially 450 ( approximately 9000 micromol N kg-1 h-1) and 75 times ( approximately 1500 micromol N kg-1 h-1) greater than basal (non-feeding) rates ( approximately 20 micromol N kg-1 h-1). In contrast, J(Urea) increased by 15-fold after parasitic lampreys were removed from non-ureosmotic rainbow trout (Oncorhynchus mykiss). Since activities of the ornithine urea cycle (OUC) enzymes, carbamoyl phosphate synthetase III (CPSase III) and ornithine carbamoyl transferase (OCT) were relatively low in liver and below detection in intestine and muscle, it is unlikely that the excreted urea arose from de novo urea synthesis. Measurements of arginase activity suggested that hydrolysis of dietary arginine made a minor contribution to J(Urea.). Post-feeding ammonia excretion rates (J(Amm)) were 15- to 25-fold greater than basal rates in lampreys removed from both basking sharks and rainbow trout, suggesting that parasitic lampreys have a high capacity to deaminate amino acids. We conclude that the sea lamprey's ability to penetrate the dermal denticle armor of sharks, to rapidly excrete large volumes of urea and a high capacity to deaminate amino acids, represent adaptations that have contributed to the evolutionary success of these phylogenetically ancient vertebrates.