A Universal Biomacromolecule-Enabled Assembly Strategy for Constructing Multifunctional Aerogels with 90% Inorganic Mass Loading from Inert Nano-Building Blocks.

Inert inorganic nano-building blocks, such as carbon nanotubes (CNTs) and boron nitride (BN) nanosheets, possess excellent physicochemical properties. However, it remains challenging to build aerogels with these inert nanomaterials unless they are chemically modified or compounded with petrochemical polymers, which affects their intrinsic properties and is usually not environmentally friendly. Here, a universal biomacromolecule-enabled assembly strategy is proposed to construct aerogels with 90 wt% ultrahigh inorganic loading. The super-high inorganic content is beneficial for exploiting the inherent properties of inert nanomaterials in multifunctional applications. Taking chitosan-CNTs aerogel as a proof-of-concept demonstration, it delivers sensitive pressure response as a pressure sensor, an ultrahigh sunlight absorption (94.5%) raising temperature under light (from 25 to 71 °C within 1 min) for clean-up of crude oil spills, and superior electromagnetic interference shielding performance of up to 68.9 dB. This strategy paves the way for the multifunctional application of inert nanomaterials by constructing aerogels with ultrahigh inorganic loading.

Programmable Electrical Signals Induce Anisotropic Assembly of Multilayer Chitosan Hydrogels.

Multilayer hydrogels are widely used in biomedical-related fields due to their complex and variable spatial structures. Various strategies have been developed for preparing multilayer hydrogels, among which electrically induced self-assembly provides a simple and effective method for multilayer hydrogel fabrication. By application of an oscillatory electrical signal sequence, multilayer hydrogels with distinct boundaries can be formed according to the provided programmable signals. In this work, we establish an electrical field in microfluidics combined with polarized light microscopy for in situ visualization of anisotropic construction of multilayer chitosan hydrogel. The noninvasive, real-time birefringence images allow us to monitor the orientation within the hydrogel in response to electrical signals. An increased birefringence was observed from the solution-gel side to the electrode surface side, and a brief electrical signal interruption did not affect the anisotropic assembly process. This understanding of the oscillatory electrical signal-induced hydrogel anisotropy assembly allows us to fabricate chitosan hydrogels with a complex and spatially varying structure.

Janus Fibrous Mats Based Suspended Type Evaporator for Salt Resistant Solar Desalination and Salt Recovery.

Solar desalination has been recognized as an emerging strategy for solving the pressing global freshwater crisis. However, salt crystallization at the photothermal interface frequently causes evaporator failure. In addition, arbitrary discharge of concentrated brine produced during desalination results in potential ecological impacts as well as wastage of valuable minerals. In the present work, a suspended-type evaporator (STEs) constructed using Janus fibrous mats is reported. The fibrous structure wicks brine to the evaporation layer and the salt gets confined in the evaporation layer until crystallization for zero liquid discharge due to the suspended design. Enhanced evaporation is observed because STEs have an additional low-resistance vapor escape path directly from the evaporation layer to the atmosphere compared to traditional floating Janus evaporators. Moreover, owing to the drastically different wettability on both sides, the evaporator allows salt crystallization only on the hydrophilic bottom layer, thus eliminating salt accumulation at the hydrophobic photothermal interface. With this unique structural design, the proposed evaporator not only maintains a high evaporation rate of 1.94 kg m-2 h-1 , but also demonstrates zero liquid discharged salt resistance and ideal recovery of the mineral in brine.

Long non-coding RNA GAS5 regulates Th17/Treg imbalance in childhood pneumonia by targeting miR-217/STAT5.

The imbalance of helper T (Th) 17 and regulatory T (Treg) cells plays an important role in the pathogenesis of pneumonia. This study aims to investigate the role and mechanism of long non-coding RNA growth arrest-specific 5 (GAS5) in the differentiation of Th17 cells and Tregs in childhood pneumonia. Expression of GAS5, miR-217, signal transducer and activator of transcription-5 (STAT5), receptor-related orphan receptor γt (RORγt), and transcription factor Forkhead box P3 (Foxp3) were examined by qRT-PCR and western blot. The percentage of Th17 cells and Tregs in CD4+ T cells were measured by flow cytometry. The interaction between miR-217 and GAS5 or STAT5 was analyzed by luciferase reporter assay. Downregulated GAS5 expression and Treg cell percentage, and upregulated Th17 cell percentage were observed in pneumonia patients when compared with the healthy controls. Furthermore, GAS5 overexpression corrected the imbalanced Th17/Treg in peripheral blood CD4+ T cells derived from pneumonia patients, and this effect was reversed by miR-217 mimic and STAT5 silencing. Mechanistically, GAS5 acted as a sponge of miR-217 to reduce binding of miR-217 to its target STAT5, leading to upregulation of STAT5 expression. Taken together, GAS5 corrects the Treg/Th17 imbalance by targeting the miR-217/STAT5 axis in childhood pneumonia.

Electrical Writing to Three-Dimensional Pattern Dynamic Polysaccharide Hydrogel for Programmable Shape Deformation.

The ability to pattern and actuate hydrogels is essential for biomimetics, soft robotics, and biosensors. Here an electrical writing technique with the capability to create both surface and across thickness patterns in dynamic chitosan-H+ /agarose hydrogel by electronically generated pH gradient is introduced. The diffusible pH cues deprotonate and re-assemble chitosan chains by hydrogen bonds, changing the electrical writing domains from original loose structure to a dense layer and resulting in different mechanical stress and swell ability that causes the hydrogel to deform. The deformable trend can be modulated by writing depth and selective writing area on the surface, and significantly enhanced by temperature increment. Finally, a dual electrical writing process to create three-dimensional patterns and demonstrate programmable shape transition by differing patterns is performed.

Preparation and in vitro antioxidant activities of 6-amino-6-deoxychitosan and its sulfonated derivatives.

The 6-amino-6-deoxychitosan (NC) and their 2, 6-di-N-sulfonated derivatives were prepared via N-phthaloylation, tosylation, azidation, hydrazinolysis, reduction of azide groups and N-sulfonation, and their structures were systematically characterized by FT-IR, 2D HSQC NMR, XRD, gel permeation chromatography (GPC), and elemental analysis. The 6-amino-6-deoxychitosan showed effect in three selected antioxidant essays, including reducing power, superoxide anion radical scavenging ability, and hydroxyl radical scavenging effect. But the factors affecting each activity were different. The reducing power and the superoxide anion radical scavenging ability of NC were strong and closely related to the amino groups in the molecular chains. Both introducing N-sulfonated groups into NC and the concentration reduction of NC and its sulfonated derivatives decreased these activities. For the superoxide anion radical, the molecular charge property was also a significant influence factor. For the hydroxyl radical, NC only showed weak scavenging activity in a special inverse concentration-dependent manner. However, the incorporation of N-sulfonated groups significantly improved the scavenging activity, and the more N-sulfonated groups, the higher the concentrations, the stronger the activity was. The results could be due to the different conformations of NC and its sulfonated derivatives in aqueous solution.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)] benzoylurea induces cell-cycle arrest and apoptosis in human cancer cells.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)]benzoylurea (SUD) is a novel synthesized benzoylurea derivative. We selected several human cancer cell lines to investigate whether SUD can inhibit the growth of cancer cells. We selected the liver cell line L-02 to investigate the effect of SUD on the normal cells. Flow cytometric analysis was used to detect the effect of SUD on cell cycle, Hoechst 33258 staining was used to evaluate the apoptosis induced by SUD, real-time fluorescence quantitative PCR was used to investigate the expression of the cell cycle-relevant and apoptosis-relevant genes, a reactive oxygen species (ROS) assay was used to observe the production of ROS, and western blotting was used to determine the level of cell cycle-relevant and apoptosis-relevant proteins. According to the results of the MTT assay, the growth of human cancer cell lines was significantly inhibited by SUD treatment in a time-dependent and concentration-dependent manner; however, the growth of human normal cells was not significantly inhibited by SUD treatment. The results of flow cytometric analyses showed that SUD induced cell-cycle arrest at the G2-phase in MCF-7 cells and at the G1-phase in BGC-823 cells. The results of Hoechst 33258 staining showed that SUD induced apoptosis in MCF-7 and BGC-823 cells. The results of the ROS assay showed that the production of ROS was increased by SUD in MCF-7 and BGC-823 cells. Our research suggests that the growth-inhibitory effect of SUD on MCF-7 cells was related to G2-phase arrest, which was associated with the upregulated expression of p53 and Chk1 proteins, and downregulation of the cyclin B1 gene, cdc25a, and cyclin-dependent kinase 1 (CDK1) proteins; the growth-inhibitory effect of SUD on BGC-823 cells was related to G1-phase arrest, which was associated with upregulation of the p53 gene and Chk1 protein and downregulation of cdc25a protein and the CDK4 gene. SUD also induced apoptosis in MCF-7 and BGC-823 cell lines through the mitochondrial pathway in a p53-dependent manner.

A dynamic and self-crosslinked polysaccharide hydrogel with autonomous self-healing ability.

Natural polymeric hydrogels with self-healing capability that can recover the functionalities and structures of gels after damage are extremely attractive due to their emerging applications in the biomedical field. Here we report a self-healable polymeric hydrogel by self-crosslinking two natural polymers acrylamide-modified chitin (AMC) containing amino groups and oxidized alginate containing dialdehyde groups. The generation of the self-crosslinked hydrogel relies on the dynamic covalent linkage through Schiff base between the polysaccharide chains. The self-healing capability of the crosslinked hydrogel depends on the molar ratio of AMC and oxidized alginate and the surrounding pH. Under certain circumstances, the damaged hydrogel shows a complete recovery and can be stretched to a favorable extent, which is seldom observed for polysaccharide self-healing hydrogel. Notably, we find that the self-healing ability can be "stored" by freeze-drying and "activated" by rehydration. In addition, we demonstrate that the hydrogel can be used as a soft template to guide the repair of inorganic materials like hydroxyapatite. We anticipate that this self-healable hydrogel consisting of biocompatible and biodegradable polysaccharides can be applied to various biomedical fields.

Investigating the in vitro stereoselective metabolism of m-nisoldipine enantiomers: characterization of metabolites and cytochrome P450 isoforms involved.

m-Nisoldipine, as a novel 1,4-dihydropyridine calcium ion antagonist, was presented as a couple of enantiomers [(-), (+)-m-nisoldipine]. In this report, the in vitro metabolism of m-nisoldipine enantiomers was investigated in rat liver microsomes (RLM) by the combination of two liquid chromatography mass spectrometric techniques for the first time. The metabolites were separated and assayed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and further identified by comparison of their mass and chromatographic behaviors with reference substances. A total of 18 metabolites of (-)-m-nisoldipine and 16 metabolites of (+)-m-nisoldipine were detected, respectively, which demonstrated that (+)-m-nisoldipine is more metabolically stable than (-)-m-nisoldipine. In addition, the identified metabolic pathways of m-nisoldipine enantiomers were involved in dehydrogenation, oxidation and ester hydrolysis. Afterwards, based on high-performance liquid chromatography coupled to triple quadrupole linear ion trap mass spectrometry, various selective cytochrome P450 (CYP) enzyme inhibitors were employed to evaluate CYP isoforms. The results indicated that the inhibitors of CYP1A1/2, CYP2B1/2, 2D and 2C11 had no obvious inhibitory effects, yet the inhibitor of CYP 3A had a significant inhibitory effect on metabolism of m-nisoldipine enantiomers. This showed that CYP 3A might primarily metabolize m-nisoldipine in RLM.

Coding for hydrogel organization through signal guided self-assembly.

Complex structured soft matter may have important applications in the field of tissue engineering and biomedicine. However, the discovery of facile methods to exquisitely manipulate the structure of soft matter remains a challenge. In this report, a multilayer hydrogel is fabricated from the stimuli-responsive aminopolysaccharide chitosan by using spatially localized and temporally controlled sequences of electrical signals. By programming the imposed cathodic input signals, chitosan hydrogels with varying layer number and thickness can be fabricated. The inputs of electrical signals induce the formation of hydrogel layers while short interruptions create interfaces between each layer. The thickness of each layer is controlled by the charge transfer (Q = ∫idt) during the individual deposition step and the number of multilayers is controlled by the number of interruptions. Scanning electron micrographs (SEMs) reveal organized fibrous structures within each layer that are demarcated by compact orthogonal interlayer structures. This work demonstrates for the first time that an imposed sequence of electrical inputs can trigger the self-assembly of multilayered hydrogels and thus suggests the broader potential for creating an electrical "code" to generate complex structures in soft matter.

Dopamine-Modified Chitosan Patterning Hydrogel with Dynamic Information Storage Ability.

The storage of dynamic information in hydrogels has aroused considerable interest regarding the multiple responsiveness of soft matter. Herein, we propose an electrical writing methodology to prepare dopamine (DA)-modified chitosan hydrogels with a dynamic information storage ability. A pH-responsive chitosan hydrogel medium was patterned by cathodic writing to in situ generate OH- in the writing area, at which dopamine underwent an auto-oxidation reaction in the locally alkaline environment to generate a dark color. The patterned information on the hydrogel can be encoded simply by electrical signals. The speed of information retrieval is positively correlated with the charge transfer during the electrical writing process, and the hiding of information is negatively correlated with the environmental stimulus (i.e., dopamine concentration, pH value, etc.). To showcase the versatility of this medium for information storage and the precision of the pattern, a quick response (QR) code is electronically written on dopamine-modified chitosan hydrogel and can be recognized programmably by a standard mobile phone. The results show that electrical regulation is a novel means to program the information storage process of hydrogels, which inspires future research on structural and functional information storage using stimulus-responsive hydrogels.

Activating Adsorption Sites of Waste Crayfish Shells via Chemical Decalcification for Efficient Capturing of Nanoplastics.

The property of being stubborn and degradation resistant makes nanoplastic (NP) pollution a long-standing remaining challenge. Here, we apply a designed top-down strategy to leverage the natural hierarchical structure of waste crayfish shells with exposed functional groups for efficient NP capture. The crayfish shell-based organic skeleton with improved flexibility, strength (14.37 to 60.13 MPa), and toughness (24.61 to 278.98 MJ m-3) was prepared by purposefully removing the inorganic components of crayfish shells through a simple two-step acid-alkali treatment. Due to the activated functional groups (e.g., -NH2, -CONH-, and -OH) and ordered architectures with macropores and nanofibers, this porous crayfish shell exhibited effective removal capability of NPs (72.92 mg g-1) by physical interception and hydrogen bond/electrostatic interactions. Moreover, the sustainability and stability of this porous crayfish shell were demonstrated by the maintained high-capture performance after five cycles. Finally, we provided a postprocessing approach that could convert both porous crayfish shell and NPs into a tough flat sheet. Thus, our feasible top-down engineering strategy combined with promising posttreatment is a powerful contender for a recycling approach with broad application scenarios and clear economic advantages for simultaneously addressing both waste biomass and NP pollutants.

Electrically induced anisotropic assembly of chitosan with different molecular weights.

Anisotropic hydrogel is emerging as an important soft matter in the field of bionics and bioactuators, owing to its outstanding mechanical toughness and strength. Understanding the dynamic construction process of anisotropic hydrogel is beneficial for matching subsequent application. In this work, we establish an electrical field in microfluidics for the in-situ real time visualization of anisotropic assembly of chitosan, an amino polysaccharide. Polarized light microscopy is adopted to observe the dynamic growth of chitosan with different molecular weights. The results demonstrate that electrical signal has a profound influence on anisotropic assembly process of chitosan. It is interesting to notice that high oriented structure can be found in chitosan hydrogel with large molecular weight, which exhibits a dense and compact structure. This work provides a new perspective for predicting and controlling the formation of different molecular weights anisotropic chitosan hydrogels, which permit the rational design of chitosan hydrogels with excellent mechanical properties and specific functions.

A novel DNA detection using spherical identification probe and strand displacement reaction-initiated silver nanocluster switch.

Herein, we developed a novel fluorescent assay using spherical identification probes and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch. In this strategy, the target was captured by the spherical probes to induce the activity of exonuclease III (Exo III), catalyzing the cyclic cleavage of substrates to produce a mass of trigger strands. After magnetic bead separation, the intermediates in the supernatant activated downstream toehold-mediated strand displacement reaction to change the structure of silver nanocluster templates, leading to fluorescence intensity reduction. Furthermore, it is demonstrated that the application of spherical identification probes could reduce the signal leakage and the limit of detection. In addition, AgNCs with perfect optical property were ingeniously combined to realize signal output, which reduced the cost and time of synthesis. Under the optimal conditions, the sensing method displayed a good linear range from 250 pM to 25 nM with a detectable minimum concentration of 250 pM. And the practical application potential in complex biological matrices was also evaluated. Considering these advantages, this constructed strategy opens a new path for nucleic acid detection with better performance. A simple, label- and hairpin-free fluorescent system based on spherical identification probe and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch was successfully constructed to detect target DNA.

A fluorescent sensor based on strand displacement amplification and primer exchange reaction coupling for label-free detection of miRNA.

MicroRNAs (miRNAs) are closely associated with human disease occurrence, including cancers, diabetes, inflammation, heart diseases, and viral infections, and their rapid and accurate detection is vital for the diagnosis and treatment of these diseases. Based on one-step reaction of strand displacement amplification (SDA) and primer exchange reaction (PER), a label-free and highly sensitive miRNA-21 detection strategy was developed. In this strategy, the target miRNA-21 binds directly to the hairpin template, triggering the SDA reaction and generating a large number of single strand DNAs as primers for PER amplification. With the help of polymerase, plenty of G-quadruplex fragments of different lengths were accumulated, and the organic dye thioflavin T selectively binds to these G-quadruplex fragments to produce a strong fluorescent signal. There is a wide detection range in this method, miRNA-21 can be detected in the range of 10 fM - 1 nM, the detection limit is low (1.25 fM). This method has good specificity and can effectively distinguish single-base mismatches of miRNA. In addition, the versatility of the method was validated by changing the target recognition site of SDA template.

Silk fibroin-chitosan aerogel reinforced by nanofibers for enhanced osteogenic differentiation in MC3T3-E1 cells.

Proper bone scaffolds should be biocompatible, mechanically robust and porous for cell migration. Here, pure silk fibroin (SF)- chitosan (CS) aerogel scaffolds reinforced with different amount of SF nanofibers (SF-CS/NF1%, SF-CS/NF2% and SF-CS/NF3%) are prepared for bone regeneration. Surface morphology and composition were analyzed to ensure successful integration of each component. Incorporating 3 % nanofibers endowed the aerogels with a resistance to 3.5 times the compressive stress of the pure SF-CS aerogels. The benefits of nanofibers were also confirmed by the high porosity of 72.3 ± 1.3 %, the regulated pore size and the high-water uptake ratio of 1770.4 ± 156.8 %. Enhanced cell viability of the aerogel scaffolds was verified with Cell Counting Kit-8 (CCK-8) assays, and confocal microscopy and scanning electron microscopy (SEM) images were taken to assess the cell migration and distribution. The cell differentiation on the aerogel scaffolds was evaluated with enzyme-linked immunosorbent assay (ELISA). Significantly higher level of Collagen type I (Col-I), osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) expression was observed on SF-CS/NF3% aerogels. This biocompatible nanofiber-reinforced aerogel scaffold facilitates osteogenic differentiation by rougher surface, enhanced mechanical strength and well-regulated pores. Thus, as-prepared scaffolds may be further applied in bone regeneration field.

Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration.

Injective thermosensitive hydrogels are considered promising scaffolds to trigger dental pulp regeneration in devitalized human teeth. In this study, we developed a hydroxypropyl chitin (HPCH)/chitin whisker (CW) thermosensitive hydrogel with enhanced mechanical properties and biological activities. Exosomes can serve as biomimetic tools for tissue engineering, but the rapid clearance of unconjugated exosomes in vivo limits their therapeutic effects. To address this challenge, exosomes were isolated from human pulp stem cells (hDPSCs) and directly embedded into the HPCH/CW pre-gel to form an exosome-loaded hydrogel (HPCH/CW/Exo). The exosome-loaded thermosensitive hydrogel can be easily injected into an irregular endodontic space and gelated in situ. In vitro cell experiments proved that the delivery of exosomes significantly improved the ability of hydrogels to promote odontogenesis and angiogenesis. Meanwhile, in vivo animal experiments revealed the formation of new dental pulp-like tissues in an implanted tooth root model. Therefore, the proposed hydrogel provides a great potential alternative to traditional root canal therapy in dental clinics.

Long-term antibacterial activity by synergistic release of biosafe lysozyme and chitosan from LBL-structured nanofibers.

Biosafe antibacterial agents are urgently demanded in treating infection especially chronic infection. However, efficient and controlled release of those agents remains great challenging. Two nature-derived agents, lysozyme (LY) and chitosan (CS), are selected to establish a facile method for long-term bacterial inhibition. We incorporated LY into the nanofibrous mats, then deposited CS and polydopamine (PDA) on the surface by layer-by-layer (LBL) self-assembly. In this vein, LY is gradually released with the degradation of nanofibers, and CS is rapidly disassociated from the nanofibrous mats to synergistically result in a potent inhibition against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) over a period of 14 days. Besides long-term antibacterial capacity, LBL-structured mats could readily achieve a strong tensile stress of 6.7 MPa with an increase percentage of up to 103%. The enhanced proliferation of L929 cells arrives at 94% with help of CS and PDA on the surface of nanofibers. In this vein, our nanofiber has a variety of advantages including biocompatibility, strong long-term antibacterial effect, and skin adaptability, revealing the significant potential to be used as highly safe biomaterial for wound dressings.

Antifatigue Hydration-Induced Polysaccharide Hydrogel Actuators Inspired by Crab Joint Wrinkles.

Joint wrinkles in animals facilitate frequent bending and contribute to the duration of the joint. Inspired by the morphology and function of joint wrinkles, we developed a bionic hydration-induced polymeric actuator with constructed wrinkles at the selected area. Specifically, we adopt electrical writing to create defined single and double cross-linking regions on chitosan (CS) hydrogel. The covalent cross-linking network was constructed by electrical writing-induced covalent cross-linking between CS chains and epichlorohydrin. Subsequent treatment of sodium dodecyl sulfate allows electrostatic cross-linking at the unwritten area with the simultaneous formation of surface wrinkles. The resulting single and double cross-linking hydrogel demonstrates spontaneous deformation behaviors by the influx and efflux of H2O to the electrostatic cross-linking domain under different ion concentrations. Importantly, the wrinkle structure endows the hydrogel with extraordinary antifatigue bending performance. By regulating the surface morphology and spatial cross-linking, we can design novel biomimetic polysaccharide hydrogel actuators with fascinating functions.

Carboxymethyl chitosan assembled piezoelectric biosensor for rapid and label-free quantification of immunoglobulin Y.

Immunoglobulin Y (IgY) proves advantageous to IgG in prophylaxis and diagnosis. Quantification of IgY is therefore becoming a topic of interest. Here, we demonstrate a piezoelectric biosensor with carboxymethyl chitosan (CMCS) as the immobilization matrix. Gelation and hydrophilic nature of CMCS are favored to form a crosslinked matrix for antibody immobilization, and a comparison was made between carboxymethyl cellulose (CMC) and CMCS to investigate the benefits of such substitution. Calibration from 500 ng/mL to 200 µg/mL was established in buffer with the detection limit (LOD) down to 270 ng/mL, confirming its feasibility. As-prepared biosensor effectively prevents non-specific binding of bovine serum albumin (BSA) and lysozyme. Each real-time assay took 15 min including sensor regeneration, which can be further reduced to 4 min for signal readout only, ready for both repeated measurements after regeneration and disposable devices. Thus, as-prepared biosensor offers a rapid, label-free and cost-effective approach for IgY quantification.