A facile method to fabricate versatile keratin cryogels for tissue engineering applications.

Human hair keratin (HHK) has been extensively explored as a biomaterial for soft tissue regeneration due to their excellent bioactivity and biocompatibility. The possibility to fabricate HHK into three-dimensional (3D) hydrogels with physical properties resembling soft tissues has been well demonstrated. However, conventional keratin hydrogels often exhibit a dense architecture that could hinder cell filtration. In the present study, HHK-based cryogels were fabricated using a freeze-thaw (FT) method, where oxidized dopamine (ODA) was employed to covalently crosslink thiol/amine rich-keratin molecules at sub-zero temperatures. The obtained HHK-ODA cryogels have micron-sized pores ranging between 100 and 200 µm and mechanical properties that can be tuned by varying the crosslinking density between ODA and HHK. Through optimization of the weight content of ODA and the number of FT cycles, the compressive strengths and stiffnesses of these cryogels achieved 15-fold increments from ∼1.5 kPa to ∼22 kPa and ∼300 Pa to ∼5000 Pa, respectively. The HHK-ODA cryogels competently supported human dermal fibroblast spreading and proliferation. Overall, this study exhibited a facile method to fabricate mechanically superior keratin-based cryogels with cell compatible microarchitecture, circumventing the need for complicated chemical modifications and the use of cytotoxic crosslinkers.

Benefit analysis of multi-approach biomass energy utilization toward carbon neutrality.

To reduce greenhouse gas (GHG) emissions, biomass has been increasingly developed as a renewable and clean alternative to fossil fuels because of its carbon-neutral characteristics. China has been investigating the rational development and use of bioenergy for developing its clean energy and achieving carbon neutrality. Substituting fossil fuels with multi-source and multi-approach utilized bioenergy and corresponding carbon reduction in China remain largely unexplored. Here, a comprehensive bioenergy accounting model with a multi-dimensional analysis was developed by combining spatial, life cycle, and multi-path analyses. Accordingly, the bioenergy production potential and GHG emission reduction for each distinct type of biomass feedstock through different conversion pathways were estimated. The sum of all available organic waste (21.55 EJ yr-1) and energy plants on marginal land (11.77 EJ yr-1) in China produced 23.30 EJ of bioenergy and reduced 2,535.32 Mt CO2-eq emissions, accounting for 19.48% and 25.61% of China's total energy production and carbon emissions in 2020, respectively. When focusing on the carbon emission mitigation potential of substituting bioenergy for conventional counterparts, bioelectricity was the most effective, and its potential was 4.45 and 8.58 times higher than that of gaseous and liquid fuel alternatives, respectively. In this study, life cycle emission reductions were maximized by a mix of bioenergy end uses based on biomass properties, with an optimal 78.56% bioenergy allocation from biodiesel, densified solid biofuel, biohydrogen, and biochar. The main regional bioenergy GHG mitigation focused on the Jiangsu, Sichuan, Guangxi, Henan, and Guangdong provinces, contributing to 31.32% of the total GHG mitigation potential. This study provides valuable guidance on exploiting untapped biomass resources in China to secure carbon neutrality by 2060.

Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers.

Genomic analysis has demonstrated that many fungi possess essential gene clusters for the production of previously unobserved secondary metabolites; however, these genes are normally reduced or silenced under most conditions. These cryptic biosynthetic gene clusters have become treasures of new bioactive secondary metabolites. The induction of these biosynthetic gene clusters under stress or special conditions can improve the titers of known compounds or the production of novel compounds. Among the inducing strategies, chemical-epigenetic regulation is considered a powerful approach, and it uses small-molecule epigenetic modifiers, which mainly act as the inhibitors of DNA methyltransferase, histone deacetylase, and histone acetyltransferase, to promote changes in the structure of DNA, histones, and proteasomes and to further activate cryptic biosynthetic gene clusters for the production of a wide variety of bioactive secondary metabolites. These epigenetic modifiers mainly include 5-azacytidine, suberoylanilide hydroxamic acid, suberoyl bishydroxamic acid, sodium butyrate, and nicotinamide. This review gives an overview on the method of chemical epigenetic modifiers to trigger silent or low-expressed biosynthetic pathways to yield bioactive natural products through external cues of fungi, mainly based on the research progress in the period from 2007 to 2022. The production of about 540 fungal secondary metabolites was found to be induced or enhanced by chemical epigenetic modifiers. Some of them exhibited significant biological activities such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activity.

UvSorA and UvSorB Involved in Sorbicillinoid Biosynthesis Contribute to Fungal Development, Stress Response and Phytotoxicity in Ustilaginoidea virens.

Ustilaginoidea virens (teleomorph: Villosiclava virens) is an important fungal pathogen that causes a devastating rice disease. It can produce mycotoxins including sorbicillinoids. The biosynthesis and biological functions of sorbicillinoids have not been reported in U. virens. In this study, we identified a sorbicillinoid biosynthetic gene cluster in which two polyketide synthase genes UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens. In ∆UvSorA and ∆UvSorB mutants, the mycelial growth, sporulation and hyphal hydrophobicity were increased dramatically, while the resistances to osmotic pressure, metal cations, and fungicides were reduced. Both phytotoxic activity of rice germinated seeds and cell wall integrity were also reduced. Furthermore, mycelia and cell walls of ∆UvSorA and ∆UvSorB mutants showed alterations of microscopic and submicroscopic structures. In addition, feeding experiment showed that sorbicillinoids could restore mycelial growth, sporulation, and cell wall integrity in ∆UvSorA and ∆UvSorB mutants. The results demonstrated that both UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens, and contributed to development (mycelial growth, sporulation, and cell wall integrity), stress responses, and phytotoxicity through sorbicillinoid mediation. It provides an insight into further investigation of biological functions and biosynthesis of sorbicillinoids.

Hydroxyapatite nanoparticles-cell interaction: New approaches to disclose the fate of membrane-bound and internalised nanoparticles.

Hydroxyapatite nanoparticles are popular tools in bone regeneration, but they have also been used for gene delivery and as anticancer drugs. Understanding their mechanism of action, particularly for the latter application, is crucial to predict their toxicity. To this end, we aimed to elucidate the importance of nanoparticle membrane interactions in the cytotoxicity of MG-63 cells using two different types of nanoparticles. In addition, conventional techniques for studying nanoparticle internalisation were evaluated and compared with newer and less exploited approaches. Hydroxyapatite and magnesium-doped hydroxyapatite nanoparticles were used as suspensions or compacted as specular discs. Comparison between cells seeded on the discs and those supplemented with the nanoparticles allowed direct interaction of the cell membrane with the material to be ruled out as the main mechanism of toxicity. In addition, standard techniques such as flow cytometry were inconclusive when used to assess nanoparticles toxicity. Interestingly, the use of intracellular calcium fluorescent probes revealed the presence of a high number of calcium-rich vesicles after nanoparticle supplementation in cell culture. These structures could not be detected by transmission electron microscopy due to their liquid content. However, by using cryo-soft X-ray imaging, which was used to visualise the cellular ultrastructure without further treatment other than vitrification and to quantify the linear absorption coefficient of each organelle, it was possible to identify them as multivesicular bodies, potentially acting as calcium stores. In the study, an advanced state of degradation of the hydroxyapatite and magnesium-doped hydroxyapatite nanoparticles within MG-63 cells was observed. Overall, we demonstrate that the combination of fluorescent calcium probes together with cryo-SXT is an excellent approach to investigate intracellular calcium, especially when found in its soluble form.

Enhancing Agrichemical Delivery and Plant Development with Biopolymer-Based Stimuli Responsive Core-Shell Nanostructures.

The inefficient delivery of agrichemicals in agrifood systems is among the leading cause of serious negative planetary and public health impacts. Such inefficiency is mainly attributed to the inability to deliver the agrichemicals at the right place (target), right time, and right dose. In this study, scalable, biodegradable, sustainable, biopolymer-based multistimuli responsive core-shell nanostructures were developed for smart agrichemical delivery. Three types of responsive core/shell nanostructures incorporated with model agrichemicals (i.e., CuSO4 and NPK fertilizer) were synthesized by coaxial electrospray, and the resulting nanostructures showed spherical morphology with an average diameter about 160 nm. Tunable agrichemical release kinetics were achieved by controlling the surface hydrophobicity of nanostructures. The pH and enzyme responsiveness was also demonstrated by the model analyte release kinetics (up to 7 days) in aqueous solution. Finally, the efficacy of the stimuli responsive nanostructures was evaluated in soil-based greenhouse studies using soybean and wheat in terms of photosynthesis efficacy and linear electron flow (LEF), two important metrics for seedling development and health. Findings confirmed plant specificity; for soybean, the nanostructures resulted in 34.3% higher value of relative chlorophyll content and 41.2% higher value of PS1 centers in photosystem I than the ionic control with equivalent agrichemical concentration. For wheat, the nanostructures resulted in 37.6% higher value of LEF than the ionic agrichemicals applied at 4 times higher concentration, indicating that the responsive core-shell nanostructure is an effective platform to achieve precision agrichemical delivery while minimizing inputs. Moreover, the Zn and Na content in the leaves of 4-week-old soybean seedlings were significantly increased with nanostructure amendment, indicating that the developed nanostructures can potentially be used to modulate the accumulation of other important micronutrients through a potential biofortification strategy.

Recent Advances in Sorbicillinoids from Fungi and Their Bioactivities (Covering 2016-2021).

Sorbicillinoids are a family of hexaketide metabolites with a characteristic sorbyl side chain residue. Sixty-nine sorbicillinoids from fungi, newly identified from 2016 to 2021, are summarized in this review, including their structures and bioactivities. They are classified into monomeric, dimeric, trimeric, and hybrid sorbicillinoids according to their basic structural features, with the main groups comprising both monomeric and dimeric sorbicillinoids. Some of the identified sorbicillinoids have special structures such as ustilobisorbicillinol A, and sorbicillasins A and B. The majority of sorbicillinoids have been reported from fungi genera such as Acremonium, Penicillium, Trichoderma, and Ustilaginoidea, with some sorbicillinoids exhibiting cytotoxic, antimicrobial, anti-inflammatory, phytotoxic, and α-glucosidase inhibitory activities. In recent years, marine-derived, extremophilic, plant endophytic, and phytopathogenic fungi have emerged as important resources for diverse sorbicillinoids with unique skeletons. The recently revealed biological activities of sorbicillinoids discovered before 2016 are also described in this review.

Catalytic production of low-carbon footprint sustainable natural gas.

Natural gas is one of the foremost basic energy sources on earth. Although biological process appears as promising valorization routes to transfer biomass to sustainable methane, the recalcitrance of lignocellulosic biomass is the major limitation for the production of mixing gas to meet the natural gas composition of pipeline transportation. Here we develop a catalytic-drive approach to directly transfer solid biomass to bio-natural gas which can be suitable for the current infrastructure. A catalyst with Ni2Al3 alloy phase enables nearly complete conversion of various agricultural and forestry residues, the total carbon yield of gas products reaches up to 93% after several hours at relative low-temperature (300 degrees Celsius). And the catalyst shows powerful processing capability for the production of natural gas during thirty cycles. A low-carbon footprint is estimated by a preliminary life cycle assessment, especially for the low hydrogen pressure and non-fossil hydrogen, and technical economic analysis predicts that this process is an economically competitive production process.

Anisotropic hair keratin-dopamine composite scaffolds exhibit strain-stiffening properties.

Human hair keratin (HHK) has been successfully explored as raw materials for three-dimensional scaffolds for soft tissue regeneration due to its excellent biocompatibility and bioactivity. However, none of the reported HHK based scaffolds is able to replicate the strain-stiffening capacity of living tissues when responding to large deformations. In the present study, strain-stiffening property was achieved in scaffolds fabricated from HHK via a synergistic effect of well-defined, aligned microstructure and chemical crosslinking. Directed ice-templating method was used to fabricate HHK-based scaffolds with highly aligned (anisotropic) microstructure while oxidized dopamine (ODA) was used to crosslink covalently to HHKs. The resultant HHK-ODA scaffolds exhibited strain-stiffening behavior characterized by the increased gradient of the stress-strain curve after the yield point. Both ultimate tensile strength and the elongation at break were enhanced significantly (~700 kPa, ~170%) in comparison to that of HHK scaffolds lacking of aligned microstructure or ODA crosslinking. In vitro cell culture studies indicated that HHK-ODA scaffolds successfully supported human dermal fibroblasts (HDFs) adhesion, spreading and proliferation. Moreover, anisotropic HHK-ODA scaffolds guided cell growth in alignment with the defined microstructure as shown by the highly organized cytoskeletal networks and nuclei distribution. The findings suggest that HHK-ODA scaffolds, with strain-stiffening properties, biocompatibility and bioactivity, have the potential to be applied as biomimetic matrices for soft tissue regeneration.

Production of Copolyester Monomers from Plant-Based Acrylate and Acetaldehyde.

PCTA is an important copolyester that has been widely used in our daily necessities. Currently, its monomers are industrially produced from petroleum-derived xylene. To reduce the reliance on fossil energy, we herein disclose an alternative route to access PCTA monomer (terephthalate/isophthalate=2.4/1) in 61 % overall yield using plant-based acrylate and acetaldehyde as the feedstocks. The process includes Morita-Baylis-Hillman (MBH) reaction of acetaldehyde with acrylate, subsequent one-step dehydration/Diels-Alder reaction with acrylate over H2 SO4 /SiO2 catalyst, and final Pd/C-catalyzed dehydrogenation. Besides, when varying the final step to hydrogenation, another important monomer UNOXOL™ diol (1,4-trans/1,4-cis/1,3-trans/1,3-cis=5.2/2/2.5/1) can be produced in 67 % overall yield.

Characterization of Anisotropic Human Hair Keratin Scaffolds Fabricated via Directed Ice Templating.

Human hair keratin (HHK) is successfully exploited as raw materials for 3D scaffolds for soft tissue regeneration owing to its excellent biocompatibility and bioactivity. However, most HHK scaffolds are not able to achieve the anisotropic mechanical properties of soft tissues such as tendons and ligaments due to lack of tunable, well-defined microstructures. In this study, directed ice templating method is used to fabricate anisotropic HHK scaffolds that are characterized by aligned pores (channels) in between keratin layers in the longitudinal plane. In contrast, pores in the transverse plane maintain a homogenous rounded morphology. Channel widths throughout the scaffolds range from ≈5 to ≈15 µm and are tunable by varying the freezing temperature. In comparison with HHK scaffolds with random, isotropic pore structures, the tensile strength of anisotropic HHK scaffolds is enhanced significantly by up to fourfolds (≈200 to ≈800 kPa) when the tensile load is applied in the direction parallel to the aligned pores. In vitro results demonstrate that the anisotropic HHK scaffolds are able to support human dermal fibroblast adhesion, spreading, and proliferation. The findings suggest that HHK scaffolds with well-defined, aligned microstructure hold promise as templates for soft tissues regeneration by mimicking their anisotropic properties.

Cryogelation of Human Hair Keratins.

Human hair keratins (HHK) are known for their biocompatibility and potential to regulate cell response, possibly due to the presence of the leucine-aspartic-valine cell adhesion and signaling motifs. Together with the abundance of cysteine residues in HHK, 3D HHK scaffolds are fabricated through cryogelation based on spontaneous disulfide crosslinks and noncovalent interactions. Herein, the molecular mechanism of HHK self-assembly during cryogelation is interrogated and the influence of cryogelation parameters on the properties of the resultant scaffolds is studied. With successive freeze-thaw cycles, the storage modulus (G') of HHK cryogels substantially improves from 116.4 Pa at freeze-thaw cycle 3 (FT3) to 1908.7 Pa at freeze-thaw cycle 10 (FT10). Meanwhile, it is found that complete thiol-capping of HHK samples significantly inhibits cryogel formation as compared to partially or uncapped HHK samples, suggesting the dominant role of disulfide stabilization in cryogelation. Finally, uniaxial compression tests on HHK sponges demonstrate that FT cycling, from 0 to 10, is able to improve the compression modulus of sponges by ≈12-folds. These findings show that macroscale properties of HHK cryogels can be conveniently modulated by physical parameters of cryogelation and that disulfide bonding is the main stabilizing force in HHK cryogels.

Composite Hydrogels in Three-Dimensional in vitro Models.

3-dimensional (3D) in vitro models were developed in order to mimic the complexity of real organ/tissue in a dish. They offer new possibilities to model biological processes in more physiologically relevant ways which can be applied to a myriad of applications including drug development, toxicity screening and regenerative medicine. Hydrogels are the most relevant tissue-like matrices to support the development of 3D in vitro models since they are in many ways akin to the native extracellular matrix (ECM). For the purpose of further improving matrix relevance or to impart specific functionalities, composite hydrogels have attracted increasing attention. These could incorporate drugs to control cell fates, additional ECM elements to improve mechanical properties, biomolecules to improve biological activities or any combinations of the above. In this Review, recent developments in using composite hydrogels laden with cells as biomimetic tissue- or organ-like constructs, and as matrices for multi-cell type organoid cultures are highlighted. The latest composite hydrogel systems that contain nanomaterials, biological factors, and combinations of biopolymers (e.g., proteins and polysaccharide), such as Interpenetrating Networks (IPNs) and Soft Network Composites (SNCs) are also presented. While promising, challenges remain. These will be discussed in light of future perspectives toward encompassing diverse composite hydrogel platforms for an improved organ environment in vitro.

Transformation of Nanomaterials and Its Implications in Gut Nanotoxicology.

Ingestion of engineered nanomaterials (ENMs) is inevitable due to their widespread utilization in the agrifood industry. Safety evaluation has become pivotal to identify the consequences on human health of exposure to these ingested ENMs. Much of the current understanding of nanotoxicology in the gastrointestinal tract (GIT) is derived from studies utilizing pristine ENMs. In reality, agrifood ENMs interact with their microenvironment, and undergo multiple physicochemical transformations, such as aggregation/agglomeration, dissolution, speciation change, and surface characteristics alteration, across their life cycle from synthesis to consumption. This work sieves out the implications of ENM transformations on their behavior, stability, and reactivity in food and product matrices and through the GIT, in relation to measured toxicological profiles. In particular, a strong emphasis is given to understand the mechanisms through which these transformations can affect ENM induced gut nanotoxicity.

The Synthesis of Quinazolinones from Olefins, CO, and Amines over a Heterogeneous Ru-clusters/Ceria Catalyst.

Quinazolinones, an important class of heterocyclic compounds, have been widely used in pharmaceuticals because of their biological activity. However, the efficient and economical synthesis of quinazolinones has remained a challenge. A novel synthetic approach has now been developed to produce quinazolinones from olefins, CO, and amines over heterogeneous Ru-clusters/ceria catalyst in the absence of acids, bases, and oxidants. Furthermore, H2 O is generated as the only by-product. A series of quinazolinones with aromatic or non-aromatic substituents can be obtained in yields of up to 99 %. The Ru-clusters/ceria can be reused at least four times. The analysis of the E-factor (environmental impact factor) for the synthesis of 2-ethyl quinazolinone suggests that this system is more environmentally friendly than other processes reported previously.

Synthesis of 1,4-Cyclohexanedimethanol, 1,4-Cyclohexanedicarboxylic Acid and 1,2-Cyclohexanedicarboxylates from Formaldehyde, Crotonaldehyde and Acrylate/Fumarate.

Valuable polyester monomers and plasticizers-1,4-cyclohexanedimethanol (CHDM), 1,4-cyclohexanedicarboxylic acid (CHDA), and 1,2-cyclohexanedicarboxylates-have been prepared by a new strategy. The synthetic processes involve a proline-catalyzed formal [3+1+2] cycloaddition of formaldehyde, crotonaldehyde, and acrylate (or fumarate). CHDM is produced after a subsequent hydrogenation step over a commercially available Cu/Zn/Al catalyst and a one-pot hydrogenation/oxidation/hydrolysis process yields CHDA, whereas 1,2-cyclohexanedicarboxylate is obtained by a Pd/C-catalyzed tandem decarbonylation/hydrogenation step.

A mineral layer as an effective binder to achieve strong bonding between a hydrogel and a solid titanium substrate.

Hydrogel coating has been attractive to improve titanium implants' compatibility with biological surroundings and their performance in clinic. Herein, a CaCO3 layer is fabricated at the interface of hydrogel-titanium to achieve strong interfacial bonding. This strategy does not require complicated surface modifications and has good prospects in the field of biomedical applications.

Promoting Cell Migration in Tissue Engineering Scaffolds with Graded Channels.

Ideal bone scaffolds having good biocompatibility, good biodegradability, and beneficial mechanical properties are the basis for bone tissue engineering. Specifically, cell migration within 3D scaffolds is crucial for bone regeneration of critical size defects. In this research, hydroxyapatite scaffolds with three different types of architectures (tortuous, parallel, and graded channels) are fabricated using the freeze-casting (ice-templating) method. While most studies promote cell migration by chemical factors, it can be greatly enhanced by introducing only graded channels as compared with tortuous or parallel channels. The results provide insights and guidance in designing novel scaffolds to enhance cell migration behavior for bone tissue regeneration.

Bis{2-[(2-pyrid-yl)imino-meth-yl]phenolato}copper(II).

In the title compound, [Cu(C(12)H(9)N(2)O)(2)], the Cu(II) atom lies on a crystallographic inversion center and has a nearly square-planar geometry. The Cu(II) center coordinates to the phenolic O and azomethine N atoms of the two symmetry-related 2-[(2-pyrid-yl)imino-meth-yl]phenolate ligands. The pyridyl N atoms do not coordinate to the Cu(II) atom but participate in intra-molecular C-H⋯N hydrogen bonding. π-π stacking between the benzene rings and between the pyridyl rings [centroid-centroid distances 3.8142 (5) and 3.8142 (5) Å, respectively] links the mol-ecules into a chain propagating parallel to [100].