Native Components Research Articles

Inference of genetic ancestry from a multi-gene cancer panel in Colombian women with cancer.

Cancer health disparities among racial and ethnic populations significantly burden health systems due to unequal access to early detection, treatment, and healthcare resources. These disparities lead to worse outcomes and increased costs from delayed diagnoses, advanced treatments, and prolonged care. Genetic differences can also influence cancer susceptibility and treatment response, thus analyzing genetic ancestry is essential for uncovering genetic factors that may contribute to these disparities. Utilizing data from clinical multigene cancer panels to infer genetic ancestry offers a valuable approach to understand population structure and the impact of individual ancestries in development of complex diseases. To evaluate the accuracy of global ancestry inference using genetic markers from the TruSight™ Hereditary Cancer Panel, which was used to investigate hereditary cancer syndromes in a cohort of 116 female cancer patients at the Colombian National Cancer Institute. Additionally, to compare these results with genetic ancestry estimations from traditional genome-wide markers. Our results demonstrate a strong correlation between global genetic ancestry inferred with markers captured from TruSightTM panel (4785 markers) and Whole Genome Sequencing (WGS, 8 million markers in admixed populations. The correlation values were 0.96 (p < 0.0001) for the Native American and European ancestry components, and 0.99 (p < 0.0001) for the African ancestry fraction. Genetic ancestry mean proportions in the Colombian cohort were 45.7%, 46.2%, and 8.11% for the European, the Native American, and the African components, respectively. This study demonstrates the accuracy of ancestry inference from clinical panel data offering a promising approach for understanding cancer health disparities in admixed populations.

Invagination of Giant Unilamellar Vesicles upon Membrane Mixing with Native Vesicles.

We demonstrate rapid membrane mixing between GUVs of pure lipid compositions and membrane vesicles (MVs) isolated from the plasma membrane of Vero cells, resulting in the transfer of native lipids and proteins to the GUVs. The steps involved in the membrane mixing are docking followed by membrane fusion. We show that positively charged lipids of the GUVs are essential for the docking, and the native membrane components of MVs drive the fusion. The interleaflet and lateral asymmetry and a change in the membrane tension upon the membrane mixing trigger membrane invagination. We detected outward and inward invagination sites at the rim of the GUVs within 10-40 min of the membrane mixing. The extent of the invaginations depends on the cholesterol and sphingomyelin (SM) contents in the GUVs. Cholesterol content above a critical concentration disfavors membrane invaginations, and the SM lipid is an essential molecular factor for membrane invagination.

Variants in the N-acetyltranferase 2 gene, acetylator phenotypes and their association with tuberculosis: Findings in Peruvian patients

BackgroundTuberculosis (TB) is a highly prevalent chronic infectious disease in developing countries, with Peru being one of the most affected countries in the world. The variants of the N-acetyltransferase 2 (NAT2) gene are related to xenobiotic metabolism and have potential usefulness in TB studies. AimTo determine whether NAT2 gene variants and acetylator phenotypes are associated with active TB in Peruvian patients. MethodsThis study included cases (patients with TB) and controls (population-based data). First, DNA isolation and the rs1799929, rs1799930, and rs1799931 variants of the NAT2 gene were identified using sequencing methods. Subsequently, the acetylator phenotypes, namely slow (SA), intermediate (IA), and rapid acetylation (RA), were also analyzed. ResultsThe comparison of the frequencies of the rs1799931 variant in the cases and controls revealed significant differences. Risk factors were found for both the A allele (p = 0.00; odds ratio [OR] = 3.04, 95 % confidence interval [CI]: 1.88–4.9) and AG genotype (p = 0.00; OR = 5.94, 95 % CI: 3.17–11.09). In addition, the non-rapid acetylator phenotype (SA + IA) was also found to be a risk factor (p = 0.016; OR = 3.16, 95 % CI: 1.29–7.72). ConclusionThe A allele, GA heterozygous genotype of the rs1799931 variant of the NAT2 gene, and SA + IA acetylator phenotype showed an association with increased risk for the development of TB. In addition to xenobiotic metabolism, other metabolic and immunological functions of NAT2 have also been postulated to confer susceptibility to TB in the Peruvian population owing to its characteristic high Native American component.

Биологически активные гидролизаты белков молока и их комплексы включения с циклодектринами

Enzymatic hydrolysis of dairy proteins increases their nutritional and biological value while reducing their allergenic potential. The subsequent complexation of peptides with cyclodextrins (CDs) reduces the bitterness of the hydrolyzed proteins. The research objective was to obtain hydrolysates of whey proteins and their cyclodextrin inclusion complexes with peptides, as well as to describe the peptide composition of the cleaved dairy proteins, biological activity, and sensory profile of the hydrolysates and inclusion complexes. The research featured enzymatic whey protein hydrolysates with an extensive hydrolysis degree and their inclusion complexes with β- and γ-CDs. Dairy proteins were hydrolyzed with alcalase, and the hydrolysates obtained were subjected to micro- and ultrafiltration (cut-off limit – 10 kDa). The peptide composition of the hydrolyzed proteins was determined by the methods of high-performance liquid chromatography and chromatography-mass spectrometry. The antimutagenic activity was evaluated using the Ames test whereas the antibacterial effect was studied with the impedimetric method. The antioxidant activity was detected with fluorimetry and spectrophotometry. The method of competitive enzyme immunoassay was applied to reveal the antigenic properties. The bitterness of the experimental sample s was determined by a sensory evaluation. The research delivered the optimal modes for whey protein cleavage with alcalase that made it possible to achieve efficient micro- and ultrafiltration. The resulting hypoallergenic peptide fractions and their inclusion complexes with β- and γ-CDs possessed antioxidant, antibacterial, and antimutagenic properties. The whey proteolysis and subsequent filtration with/without tindalization demonstrated a 265/589-fold decrease in the residual antigenicity. The fluorimetric method showed a 1.79/1.90-fold increase in the antioxidant activity of the hydrolysate in complexes with β- and γ-CDs. Binding of β-CDs to peptides enhanced their antimicrobial activity against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538. The hydrolysate samples with β-CDs showed less bitterness. Whey proteolysis with alcalase under optimized conditions and subsequent fractionation resulted in a product with high consumer qualities. Enzymatic hydrolysates of dairy proteins and their CD inclusion complexes were able to substitute native protein components. Their bioactive properties, good taste, and low allergenic potential mean good prospects for the functional food industry.

Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive myasthenia gravis.

There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

Retrieval-Pretrained Transformer: Long-range Language Modeling with Self-retrieval

Abstract Retrieval-augmented language models (LMs) have received much attention recently. However, typically the retriever is not trained jointly as a native component of the LM, but added post-hoc to an already-pretrained LM, which limits the ability of the LM and the retriever to adapt to one another. In this work, we propose the Retrieval-Pretrained Transformer (RPT), an architecture and training procedure for jointly training a retrieval-augmented LM from scratch and applying it to the task of modeling long texts. Given a recently generated text chunk in a long document, the LM computes query representations, which are then used to retrieve earlier chunks in the document, located potentially tens of thousands of tokens before. Information from retrieved chunks is fused into the LM representations to predict the next target chunk. We train the retriever component with a semantic objective, where the goal is to retrieve chunks that increase the probability of the next chunk, according to a reference LM. We evaluate RPT on four long-range language modeling tasks, spanning books, code, and mathematical writing, and demonstrate that RPT improves retrieval quality and subsequently perplexity across the board compared to strong baselines.

Mutual interaction of the entomopathogenic and endophytic fungus Metarhizium anisopliae with zearalenone as a native component of crude Fusarium extract

The present study revealed the consequences of the interaction of a widely used bioinsecticide and endophyte Metarhizium anisopliae with the hazardous mycotoxin zearalenone (ZEN) as a pure substance and with ZEN as a native component of a crude Fusarium extract. In the environment, microorganisms encounter a mixture of metabolites secreted by other organisms living in the same area, not single substances. The obtained results suggest that M. anisopliae, exposed to a variety of active substances produced by Fusarium graminearum, is able to eliminate ZEN. Within 14 days, M. anisopliae biotransformed 90.8% and 85.8% of ZEN as a pure substance and ZEN as a native component of the F. graminearum extract from Rice Medium (E-Fg-RM), respectively, through reduction predominantly to α-epimers of zearalenols and zearalanols, considered more estrogenic than ZEN, which can raise concerns. Compared to pure ZEN, E-Fg-RM significantly affected the production of Metarhizium secondary metabolites by increasing the destruxins amount by approximately 20–25% and reducing the swainsonine content by 96.2%. All these findings provide a possible picture of the interaction of M. anisopliae with ZEN in the wild, mainly as a result of the use of crude extract from Fusarium, which contained a mixture of different metabolites.

Scanning electron microscopy-based quantification of keratin and hyaluronic acid microstructure in electrospun scaffolds

BackgroundThe extracellular matrix (ECM) structural deficiencies in chronic wounds prevent the wounds from healing through natural physiological processes. Electrospun biocompatible polymers offer a platform to produce microstructure wound dressing materials that mimic the ECM containing various bioactives to address the deficiencies in the chronic wound healing process. Quantitative characterization of the electrospun fiber microstructure could provide valuable information on using fiber constructs to facilitate wound healing. This work employed a validated image analysis tool to quantitatively explain various parameters for the microstructure of six electrospun fiber constructs, D1{Polycaprolactone (PCL), Polyvinyl alcohol (PVA), Keratin}, D2{PCL, PVA, keratin, Co-enzyme Q10 (CoQ10)}, D3 (PCL, PVA, keratin, mupirocin), D4 (PCL, PVA, keratin, CoQ10, mupirocin, valsartan), D5 {PVA, Hyaluronic acid (HA)}, and D6 (PVA), using scanning electron microscopy imaging modality.ResultsThe fiber intersection density (FID) parameter was quantified in the formulations, e.g., 0.272% for D5 and 0.416% for D4. Orientation histograms for D1 and D6 are characteristic of isotropic materials, while orientations for D2 and D3 indicate anisotropy with 2 preferred orientations in each formulation. D4 and D5 present orientations characteristic of transversely isotropic materials. The tortuosity for D2 and D4 indicates almost straight fiber segments, in contrast with undulated fiber segments in all other formulations. Furthermore, the mean fiber diameter was quantified, e.g., 1.414 and 1.630 mm for D3 and D4, respectively.ConclusionCo-electrospun PVA/PCL microfibers offer great potential for controlled delivery of bioactives needed to accelerate the healing of chronic wounds. This image-based analysis technology quantitatively characterized different formulations of electrospun fiber scaffolds. This analysis sets the stage for future study that utilizes microstructural information in finite element biomechanical modeling, to investigate possible influence of structure-based mechanical factors on the ECM restorative potential of wound dressings. Adjustment of electrospinning conditions could produce fabricated constructs like the native ECM structural components with a functional role in wound healing.

Genomic sequencing of 10 spore-forming Bacilli strains isolated from zoo-dwelling mice.

We present the genomic sequences of 10 spore-forming bacteria from the Bacillaceae family isolated from fecal samples of mice residing in the Tisch Family Biblical Zoo, Jerusalem. These isolates suggest Bacillus bacteria are a native component of rodent gut flora, facilitating further research into gut colonization and microbiome diversity.

Development of Foam Composites from Flax Gum-Filled Epoxy Resin

In the present work, an innovative range of foams based on flax gum-filled epoxy resin was developed, reinforced or not by flax fibers. Foams and composites with different gum and epoxy resin contents were produced and their mechanical and thermal performances were characterized. To enhance the organic flax gum filler’s cross-linking, we exploited the oxidized components’ reactivity with the amine hardener (isophorone diamine). We compared the materials obtained with those derived from the native components. The flax gum and fibers were primarily characterized by chemical analysis, NMR, and FTIR to evaluate the mild oxidation of the native materials. The formation of chemical bonds between the oxidized polymer chains, epoxy resin, and hardener was evidenced by FTIR, and the materials were then studied by SEM and X-ray computed micro-tomography (CT) and submitted to mechanical and thermal tests. The relevance of the oxidation treatment was highlighted through a significant increase in density and mechanical performance (+36% and +81%, respectively, for the 100% flax gum material). The positive effect of the flax fibers on homogeneity evidenced through micro-CT analysis was also clearly addressed. This set of promising results paves the way for the future development of fully flax-based insulation composite materials.

Unraveling the outstanding catalytic efficiency of unprocessed bone-derived biochar: A deep dive into the mechanisms of native organic encapsulation and defective nitrogen doping in boosting persulfate activation for tetracycline degradation

Designing efficient non-metallic catalysts for persulfate (PS) activation has attracted broad attention due to their demonstrated immense potential in environmental remediation. In this study, unprocessed pig bone waste was successfully converted into biochars (PBCs) through a straightforward one-step pyrolysis process, which function as efficient PS catalysts for the removal of tetracycline (TC). The results revealed that the endogenous inner layer hydroxyapatite activator (IHA) and the rich native outer layer organic component wrapped with nitrogen-doped additives (OONA) found in raw bone-derived waste biomass collaborate to exert a dual effect of template and surface modification at 900 °C. Notably, under this synergistic action, 900PBC exhibited active defect nitrogen (pyridinic and graphitic nitrogen), sp2-hybridized groups (C = C, C = O, and C = N) and high defect levels (ID/IG = 1.0291), along with a cross-linked micro-mesoporous structure. This unique combination of properties endowed 900PBC with excellent catalytic activity, enabling it to effectively remove 50 mg/L of TC in the PS system within 30 min, primarily through a dual reaction pathway involving oxygen-active species (O2·-, 1O2) and electron transfer (fitting instantaneous-current values to PS concentrations, R2 = 0.95). Density-functional theory calculations confirmed that, within the nitrogen configurations located at defect sites, pyridinic nitrogen exerted a significant influence on the electron cloud density of adjacent carbon networks, subsequently promoting the formation of excited states of PS. Meanwhile, graphitic nitrogen constructed electron bridges with adjacent sp2-hybridized orbitals, facilitating the formation of the metastable complex 900PBC-PS*. Remarkably, 900PBC also exhibited excellent cyclic stability, maintaining a 93 % TC removal rate after four cycles,as well as high tolerance to a broad pH range (3–9), high concentrations of coexisting ions (10 mM), and diverse real-world water bodies. This study offers novel insights into synthesizing high-value biochar from waste bones with high catalytic activity.

Viscoelastic Supramolecular Hyaluronan-Peptide Cross-Linked Hydrogels.

Viscoelasticity plays a key role in hydrogel design. We designed a physically cross-linked hydrogel with tunable viscoelasticity, comprising supramolecular-assembled peptides coupled to hyaluronan (HA), a native extracellular matrix component. We then explored the structural and molecular mechanisms underlying the mechanical properties of a series of these HA-peptide hydrogels. By modifying the peptide sequence, we modulated both long- and short-time stress relaxation rates as a way to target viscoelasticity with limited impact on stiffness, leading to gels that relax up to 60% of stress in 10 min. Gels with the highest viscoelasticity exhibited large mesh sizes and β-sheet secondary structures. The stiffness of the gel correlated with hydrogen bonding between the peptide chains. These gels are cytocompatible: highly viscoelastic gels that mimic the native skin microenvironment promote dermal fibroblast cell spreading. Moreover, HA-peptide gels enabled cell encapsulation, as shown with primary human T cells. Overall, these physically-cross-linked hydrogels enable tunable viscoelasticity that can be used to modulate cell morphology.

Soil Chemical Quality in Integrated Production Systems with the Presence of Native and Exotic Tree Components in the Brazilian Eastern Amazon

Soil Chemical Quality in Integrated Production Systems with the Presence of Native and Exotic Tree Components in the Brazilian Eastern Amazon

Hyaluronan improves photoreceptor differentiation and maturation in human retinal organoids

Human stem cell-derived organoids enable both disease modeling and serve as a source of cells for transplantation. Human retinal organoids are particularly important as a source of human photoreceptors; however, the long differentiation period required and lack of vascularization in the organoid often results in a necrotic core and death of inner retinal cells before photoreceptors are fully mature. Manipulating the in vitro environment of differentiating retinal organoids through the incorporation of extracellular matrix components could influence retinal development. We investigated the addition of hyaluronan (HA), a component of the interphotoreceptor matrix, as an additive to promote long-term organoid survival and enhance retinal maturation. HA treatment had a significant reduction in the proportion of proliferating (Ki67+) cells and increase in the proportion of photoreceptors (CRX+), suggesting that HA accelerated photoreceptor commitment in vitro. HA significantly upregulated genes specific to photoreceptor maturation and outer segment development. Interestingly, prolonged HA-treatment significantly decreased the length of the brush border layer compared to those in control retinal organoids, where the photoreceptor outer segments reside; however, HA-treated organoids also had more mature outer segments with organized discs structures, as revealed by transmission electron microscopy. The brush border layer length was inversely proportional to the molar mass and viscosity of the hyaluronan added. This is the first study to investigate the role of exogenous HA, viscosity, and polymer molar mass on photoreceptor maturation, emphasizing the importance of material properties on organoid culture. Statement of SignificanceRetinal organoids are a powerful tool to study retinal development in vitro, though like many other organoid systems, can be highly variable. In this work, Shoichet and colleagues investigated the use of hyaluronan (HA), a native component of the interphotoreceptor matrix, to improve photoreceptor maturation in developing human retinal organoids. HA promoted human photoreceptor differentiation leading to mature outer segments with disc formation and more uniform and healthy retinal organoids. These findings highlight the importance of adding components native to the developing retina to generate more physiologically relevant photoreceptors for cell therapy and in vitro models to drive drug discovery and uncover novel disease mechanisms.

Power-efficient and high-performance potential of pentacene transistors enabled by metal-nitride gate insulators fabricated with nitrogen plasma

The demand for next-generation organic field-effect transistors (OFETs) with low operating voltage is becoming gradually attractive in many application areas, such as flexible/wearable medical sensors and stretchable electronics. While using high dielectric materials is a potent approach, it often results in a decline in field-effect mobility or on/off ratio. Unfortunately, achieving low-voltage operation has hindered practical applications, compromising device performance. Here, we discovered for the first time a novel class of low-driving voltage pentacene transistors adopting gate insulators composed of nitrogen-plasma-reacted AlNx, TiNx, and TaNx. This exciting discovery is simple, affordable, environmentally friendly, and secure. X-ray photoelectron spectrometer (XPS) analysis reveals that the as-formed metal nitrides are composited with certain native oxide components, exhibiting outstanding leakage current blocking capacity and a high dielectric constant. Further, the surface energy of metal nitrides was altered by applying a thin layer of poly-(4-vinylphenol) (PVP). This modification improved the growth of pentacene grains and the insulator/pentacene interface. The best devices by comprehensive evaluation, the TiNx samples, achieve a high average of field-effect mobility ∼1.41 cm2/Vs, a subthreshold swing of 0.19 V/dec, an on/off current ratio of ∼104, and a turn-on voltage close to 0 V, which shows promising potential candidates for the flexible electronic devices, optoelectronic devices, and neuromorphic application.

Reconstitution of a biofilm adhesin system from a sulfate-reducing bacterium in Pseudomonas fluorescens

Biofilms of sulfate-reducing bacterium (SRB) like Desulfovibrio vulgaris Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses. Although the mechanisms of biofilm formation by DvH are not yet well understood, recent studies indicate the large adhesin, DvhA, is a key determinant of biofilm formation. The dvhA gene neighborhood resembles the biofilm-regulating Lap system of Pseudomonas fluorescens but is curiously missing the c-di-GMP-binding regulator LapD. Instead, DvH encodes an evolutionarily unrelated c-di-GMP-binding protein (DVU1020) that we hypothesized is functionally analogous to LapD. To study this unusual Lap system and overcome experimental limitations with the slow-growing anaerobe DvH, we reconstituted its predicted SRB Lap system in a P. fluorescens strain lacking its native Lap regulatory components (ΔlapGΔlapD). Our data support the model that DvhA is a cell surface-associated LapA-like adhesin with a N-terminal "retention module" and that DvhA is released from the cell surface upon cleavage by the LapG-like protease DvhG. Further, we demonstrate DVU1020 (named here DvhD) represents a distinct class of c-di-GMP-binding, biofilm-regulating proteins that regulates DvhG activity in response to intracellular levels of this second messenger. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.

Interactions of Native Maize Starch Components with Pectin Using Extrusion

AbstractNative starch exhibits undesirable properties in the final product when used as an additive. Recently, the effects of the interaction between starch and hydrocolloids on the techno‐functional properties of starch have been studied. However, this interaction has not yet been applied to a real food system. Therefore, in this work, the techno‐functional properties of starch–pectin complexes formed by extrusion are investigated. Mixtures of isolated native Pozolero maize starch “HPZ1” and pectin of low degree of methyl‐esterification at four concentrations (0%, 2%, 5%, and 7%) are used. The starch–pectin blends are processed in a single screw extruder with constant variables: temperature, screw speed, and moisture. Morphology, X‐ray diffraction, thermal properties, and techno‐properties are studied. A protective effect of pectin on the starch granules is observed, as evidenced by a matrix involving starch granules. Extrusion results in a partial gelatinization of the starch granules and alters their thermal and pasting properties with the peak temperature increasing with increasing pectin concentration. Extrusion allows both carbohydrates to interact with each other. Finally, the results show that the starch–pectin complexes are ingredients with desirable techno‐functional properties that can be integrated into a food system and add value to Mexican criollo maize.

Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane-Antibiotic Interactions.

As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug-membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are chelated. This biomembrane biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.

Programmable and resilient metamaterials with anisotropic and non-linear mechanical responses composed exclusively of stiff constituents.

Recently, significant progress has been made in the field of flexible bulk metamaterials composed of soft and elastic materials, unlocking the potential for achieving programmable non-linear mechanical responses, such as shape morphing, energy absorption, and information processing. However, the majority of these metamaterials utilize expensive hyperelastic materials and require complex fabrication processes. Additionally, constructing eco-friendly stiff constituents for these metamaterials remains challenging due to their limited elastic limit strains (<0.1). Here, we propose a systematic design strategy by combining curved beams with chiral metastructures to generate a family of three-dimensional programmable resilient mechanical metamaterials without relying on flexible or hyperelastic constituents. These tiled metamaterials demonstrate robust, anisotropic and non-linear resilience under large elastic compression strains (>0.75), while exhibiting a programmable effective modulus reduction of nearly 6 orders of magnitude compared to the native stiff components. Furthermore, leveraging their stable resilience under high-frequency stimuli, we successfully developed a meter-scale soft robot capable of traversing complex narrow scenarios on demand without the need for flexible materials or sophisticated pipelines. We anticipate that these mechanical metamaterials could serve as a universal platform for programmable active dampers, modular flexible robots, and medical rehabilitation equipment at various scales.

Development and Characterization of Decellularized Lung Extracellular Matrix Hydrogels.

The use of extracellular matrix (ECM)-derived hydrogels in tissue engineering has become increasingly popular, as they can mimic cells' natural environment in vitro. However, maintaining the native biochemical content of the ECM, achieving mechanical stability, and comprehending the impact of the decellularization process on the mechanical properties of the ECM hydrogels are challenging. Here, a pipeline for decellularization of bovine lung tissue using two different protocols, downstream characterization of the effectiveness of decellularization, fabrication of reconstituted decellularized lung ECM hydrogels and assessment of their mechanical and cytocompatibility properties were described. Decellularization of the bovine lung was pursued using a physical (freeze-thaw cycles) or chemical (detergent-based) method. Hematoxylin and Eosin staining was performed to validate the decellularization and retention of major ECM components. For the evaluation of residual collagen and sulfated glycosaminoglycan (sGAG) content within the decellularized samples, Sirius red and Alcian blue staining techniques were employed, respectively. Mechanical properties of the decellularized lung ECM hydrogels were characterized by oscillatory rheology. The results suggest that decellularized bovine lung hydrogels can provide a reliable organotypicalternative to commercial ECM products by retaining most native ECM components. Furthermore, these findings reveal that the decellularization method of choice significantly affects gelation kinetics as well as the stiffness and viscoelastic properties of resulting hydrogels.