Sustainable, Insoluble, and Photonic Cellulose Nanocrystal Patches for Calcium Ion Sensing in Sweat.

Self-assembly of cellulose nanocrystals (CNCs) is invaluable for the development of sustainable optics and photonics. However, the functional failure of CNC-derived materials in humid or liquid environments inevitably impairs their development in biomedicine, membrane separation, environmental monitoring, and wearable devices. Here, a facile and robust method to fabricate insoluble hydrogels in a self-assembled CNC-polyvinyl alcohol (PVA) system is reported. Due to the reconstruction of inter- or intra-molecular hydrogen bond interactions, thermal dehydration makes an optimized CNC/PVA photonic film form a stable hydrogel network in an aqueous solution rather than dissolve. Notably, the resulting hydrogel exhibits superb mechanical performance (stress up to 3.3 Mpa and tough up to 0.73 MJ m-3 ) and reversible conversion between dry and wet states, enabling it convenient for specific functionalization. Sodium alginate (SA) can be adsorbed into the CNC photonic structure by swelling dry CNC/PVA film in a SA solution. The prepared hydrogel showcases the comprehensive properties of freezing resistance (-20°C), strong adhesion, satisfactory biocompatibility, and highly sensitive and selective Ca2+ sensing. The material could act as a portable wearable patch on the skin for the continuous analysis of calcium trends during different physical exercises, facilitating their development in precision nutrition and health monitoring.

A Sensitive Concentration- and Polarity-Dependent Pyrene-Derived Vibrationally Resolved Fluorescence Probe for The Polymer Interdiffusion Study.

The vibrationally resolved pyrene fluorescence probe method is once popular but now languished, because the vibrationally resolved patterns of pyrene with limited sensitivity and concentration independence have not been updated for over 50 years. During investigation on the polymer interdiffusion of a latex film, it is found that a pyrene acylhydrazone whose vibrationally resolved fluorescence pattern contradictory to those reported in pyrene and most pyrene derivatives. The pyrene acylhydrazone has sensitive concentration- and polarity-dependent fluorescence spectra (the sensitivity on polarity is at most 26 times higher than the old vibrationally resolved patterns), and the sensitivity well remains when it is copolymerized in a polymer. The vibrationally resolved spectrum of this pyrene acylhydrazone is a powerful fluorescence probe, which would be as useful as the pyrene excimer probe nowadays popular.

Highly Tough, Stretchable, and Solvent-Resistant Cellulose Nanocrystal Photonic Films for Mechanochromism and Actuator Properties.

Cellulose nanocrystals (CNCs)-derived photonic materials have confirmed great potential in producing renewable optical and engineering areas. However, it remains challenging to simultaneously possess toughness, strength, and multiple responses for developing high-performance sensors, intelligent coatings, flexible textiles, and multifunctional devices. Herein, the authors report a facile and robust strategy that poly(ethylene glycol) dimethacrylate (PEGDMA) can be converged into the chiral nematic structure of CNCs by ultraviolet-triggered free radical polymerization in an N,N-dimethylformamide solvent system. The resulting CNC-poly(PEGDMA) composite exhibits impressive strength (42 MPa), stretchability (104%), toughness (31 MJ m-3 ), and solvent resistance. Notably, it preserves vivid optical iridescence, displaying stretchable variation from red, yellow, to green responding to the applied mechanical stimuli. More interestingly, upon exposure to spraying moisture, it executes sensitive actuation (4.6° s-1 ) and multiple complex 3D deformation behaviors, accompanied by synergistic iridescent appearances. Due to its structural anisotropy of CNC with typical left-handedness, the actuation shows the capability to generate a high probability (63%) of right-handed helical shapes, mimicking a coiled tendril. The authors envision that this versatile system with sustainability, robustness, mechanochromism, and specific actuating ability will open a sustainable avenue in mechanical sensors, stretchable optics, intelligent actuators, and soft robots.

Copolymer-Functionalized Cellulose Nanocrystals as a pH- and NIR-Triggered Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

As a class of biocompatible and biodegradable naturally derived nanomaterials, cellulose nanocrystals (CNCs) with diverse surface functionalization have aroused considerable attention for a range of biomedical applications in drug or gene delivery, as a fluorescent nanoprobe, in cancer targeting, and in photothermal cancer therapy, among others. Herein, we construct the copolymer-functionalized CNCs as a pH- and near-infrared (NIR)-triggered drug carrier for simultaneous photothermal therapy and chemotherapy of cancer cells. Poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PCL-b-PDMAEMA) was conjugated onto the surface of CNCs through ring-opening polymerization, followed by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The resultant CNC-based drug carrier can encapsulate doxorubicin (DOX) as a therapeutic agent and indocyanine green (ICG) as an NIR dye in the PCL core and the PDMAEMA shell, respectively, via hydrophobic and electrostatic interactions. In addition to the intrinsic pH response, the release profile of DOX can also be controlled by the duration of laser irradiation due to collapse of the crystal structure of the PCL domain with the increase of temperature induced by photothermal conversion. The drug carrier can exhibit enhanced cytotoxicity toward HepG2, human hepatocyte carcinoma, cells upon laser irradiation, which can be attributed to the synergistic effect arising from NIR-triggered burst release of DOX and photothermal heating. The rod-like morphology of the CNC-based drug carrier may help accelerate the endocytosis in cell membranes compared with its common spherical counterpart. Based on the abovementioned advantages, copolymer-functionalized CNCs can serve as a promising candidate for effective cancer treatment.

Morphological transitions of micelles induced by the block arrangements of copolymer blocks: dissipative particle dynamics simulation.

Polymer micelles with distinct morphologies and unique microphase separation microstructures can exhibit different properties and functions, holding great promise for a range of biomedical applications. In the current work, the topological effects of grafted triblock copolymers on the morphologies and microphase separation microstructures of micelles, including block arrangements and grafting arrangements of hydrophobic side chains, are systematically studied. Using common copolymer components of typical drug carriers, micelles with interesting geometries are achieved, such as raspberry, multicompartment, ellipsoidal and dumbbell shapes, in which the relationship between micelle morphology and copolymer topology is verified. With further exploration of the grafting position and amount of hydrophobic side chains, the microstructure influencing mechanism of copolymer micelles in self-assembly is discussed. The block arrangements of hydrophobic side chains determine the configurations of copolymers (zigzag/bridge) inside micelles, which in turn affect the morphological transitions (from spherical to ringed short-rods and then to cylinders) and the size of the hydrophobic ring, which further gradually change into hydrophobic cage. This study provides insight into the microstructure of hydrophobic side chain grafted copolymer micelles and further helps to understand the mechanism of controlling the morphology of micelles, which might be useful to guide the molecular design and experimental preparation of micelles with controllable morphology for drug encapsulation and delivery.

[Expression of Twist1, SIRT1, FGF2 and TGF-ß3 genes and its regulatory effect on the proliferation of placenta, umbilical cord and dental pulp mesenchymal stem cells].

OBJECTIVE: To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-ß3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs). METHODS: The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-ß3. RESULTS: The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-ß3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-ß3 was observed in PA-MSCs, UC-MSCs and DP-MSCs. CONCLUSION: Up-regulated expression of the Twist1, SIRT1 and TGF-ß3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-ß3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-ß3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.

Directed Self-Assembly of Patchy Microgels into Anisotropic Nanostructures.

Multi-geometry nanostructures with high-order, complex, and controllable geometries have attracted extensive attention in the development of functional nanomaterials. A simple and versatile strategy is proposed to construct various anisotropic nanostructures through the directed self-assembly (DSA) of patchy microgels. A general criterion for interaction parameters is developed by the variance analysis method to achieve the formation of 1D nanorods by the single directional DSA process, and 2D or 3D polymorphs including V/T/h/cross shapes, multiple arms, multi-directional bending, single/multiple rings, nanocages, etc., by the multi-directional DSA process of binary microgel blends. At the optimum interaction parameters, the nanorods exhibit the quickest formation process and the most thermodynamically stable geometry, while the various 2D or 3D assemblies exhibit controlled jointing behaviors for versatile assembly geometries. The number of recognition sites on the patchy microgel surface guides the aggregation modes of microgels during the DSA process. These assemblies can bear large curvature variance with the increase of shear rates due to the high flexibility and the ability of adjusting orientation spontaneously. The DSA behavior of patchy microgels differs from the traditional self-assembly process of block copolymers, which may open a new route for guiding the formation of controllable nanoparticle architectures.

Application of PAC and flocculants for improving settling of solid particles in oilfield wastewater with high salinity and Ca2.

The suspended solids in wastewater from Rekabak oilfield, Kazakhstan, were characterized and treated with flocculants to enhance settling. The wastewater contained a high concentration of total dissolved solids and calcium ion. Scanning electron microscopy and energy dispersive X-ray analyses showed that suspended solids were mainly composed of corrosion products (iron oxides) and silicon dioxide particles. Also, much salt deposition from wastewater caused a large increase in the suspended solids value. The settling of solid particles in wastewater was investigated by turbidity decrease within 60 min. The particle settling was enhanced by adding polyaluminum chloride (PAC) as coagulant and hydrolyzed polyacryamide (HPAM) or cationic polyacrylamide (CPAM) as flocculant. At optimal dose, the particle settling ability with PAC and CPAM was better than that with PAC and HPAM. Particle size analysis showed that HPAM or CPAM with high molecular weight played an important role for enlarging the particle size. The experiments with simulated wastewater showed that particle settling by using HPAM deteriorated significantly compared to that by CPAM at high calcium ion. This study provides further understanding about the effect of high salinity and Ca2+ on solids formation, flocculant performance and particle settling. Meanwhile, the results are also helpful to develop novel flocculants used for high salinity wastewater.

[Analysis of digital gene expression profiles of the cultivated Polygala tenuifolia in different phenological phases].

The content changes of chemical components in different phenological phase of the cultivated Polygala tenuifolia is one of the important factors for determination of the best harvest time in the production practice. In this study, the digital gene expression (DGE) profiles of the cultivated P. tenuifolia were analyzed in different phenological phase (flowering fruit bearing stage, wilting stage, dormancy stage). The differentially expressed genes were found in the biosynthesis of chemical composition in P. tenuifolia, and the representational ones were validated by RT-q PCR. Then, the key enzymes(CYP450s and UGTs) involved in the downstream of the triterpenoid saponins biosynthesis pathway in P. tenuifolia were predicted through the correlation analysis of gene expression. The number of down-regulated genes was more than that of up-regulated in P. tenuifolia from flowering fruit bearing stage to dormancy stage. Six differentially expressed genes (HMGS, PMK, FPPS, SQS, SE, ß-AS) and five (PAL, C4 H, 4CL, CAD, peroxidase) were annotated to the triterpenoid saponins and phenylpropanoid biosynthesis pathway in P. tenuifolia, respectively. Compared to wilting and dormancy stages, the saponins, xanthones, and lignins were largely synthesized at the flowering fruit bearing stage of P. tenuifolia. Furthermore, UGT83A1, CYP716B1, CYP98A3, CYP86B1, and CYP94A1 may be the part of key enzymes in the downstream of the triterpenoid saponins biosynthesis pathway in P. tenuifolia. This study provides evidence to support the correctness of traditional harvest time of P. tenuifolia at the level of transcription, and lays the scientific foundation for gene cloning and functional verification of CYP450 s and UGTs in the downstream of the triterpenoid saponins biosynthesis pathway in P. tenuifolia in the future.

Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual-Histidine-Based Cell Imprinted Hydrogels.

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.

Mesoscopic Simulations of Diselenide-Containing Crosslinked Doxorubicin-Loaded Micelles and Their Tumor Microenvironment Responsive Release Behaviors.

There is currently limited research on the structure-property relationship of reduction stimuli-responsive polymeric crosslinked micelles using mesoscopic simulations. Herein, dissipative particle dynamics (DPD) simulations were used to simulate the self-assembly process of the blank non-crosslinked micelle, the structure and doxorubicin (DOX) distribution of diselenide crosslinked micelle with different crosslinker contents (CCs) based on the nearest-neighbor bonding principle. The results revealed that the formation of a three-layer spherical micelle and the loaded DOX mainly distributed in the polycaprolactone (PCL) core and hydroxyethyl methacrylate (HEMA) mesosphere. The larger the dosage of DOX, the more DOX encapsulated, but the encapsulation of DOX in the hydrophobic domain would reach saturation when the dosage increased to 6.0 %. In micelles with lower CCs or crosslinking levels (CLs), DOX entered the middle layer and the inner core faster. Then, based on the nearest media-bead bond breaking principle and subsequently DPD simulation, the effects of different CCs on the micelle structure and DOX release properties were investigated. Low CC could cause fast drug release. With the increase of CCs, the micelle showed a slower DOX release trend. The multilayer crosslinked network system also affected the DOX release rate. Hence, this work can provide some mesoscale guidance for the structural design and structure-property relationship of stimuli-responsive reversible crosslinked micelles for drug delivery.

Effects of high hydrostatic pressure on enzymes, phenolic compounds, anthocyanins, polymeric color and color of strawberry pulps.

BACKGROUND: Changes in activity of polyphenol oxidase (PPO), peroxidase (POD) and ß-glucosidase, individual phenolic compounds other than anthocyanins, total phenols, monomeric anthocyanins, polymeric color and instrumental color of strawberry pulps were assessed after high hydrostatic pressure (HHP) (400-600 MPa 5-25 min(-1)) at room temperature. RESULTS: ß-Glucosidase was activated by 4.7-16.6% at 400 MPa 5-25 min(-1) and inactivated by 8.0-41.4% at 500 or 600 MPa. PPO and POD were inactivated at all pressures, the largest reduction in activity being 41.4%, 51.5% and 74.6%, respectively. The individual phenolic compounds and total phenols decreased at 400 MPa, but total phenols increased at 500 or 600 MPa. However, the monomeric anthocyanins, polymeric color and redness (a*) exhibited no change. HHP induced a decrease in lightness (L*) and an increase in yellowness (b*) at 400 MPa, but no significant alteration in L* value and b* value at 500 or 600 MPa was observed; this was attributed to higher residual activity of PPO, POD and ß-glucosidase at 400 MPa. Total color difference (ΔE) was ≥5 at 400 MPa and ≤3 at 500 or 600 MPa. CONCLUSION: HHP effectively retained anthocyanins, phenolic compounds and color of strawberry pulps, and partly inactivated enzymes.

Mesoporous Silica Nanoprodrug Encapsulated with Near-Infrared Absorption Dye for Photothermal Therapy Combined with Chemotherapy.

Based on the tumor microenvironment with weak acidic characteristics, a nano-drug delivery system that achieves controlled release of drugs through the pH response has been a popular strategy to improve the effectiveness of tumor therapy and reduce toxic side effects, and combining photothermal therapy (PTT) on this basis can help improve the antitumor effect. In this study, mesoporous silica nanoparticles (MSNs) were surface-modified with polymer poly(PEGMA-co-HEMA) via surface-initiated atom transfer radical polymerization, and a multifunctional nanoplatform MSN@poly(PEGMA-co-HEMA-g-doxorubicin (DOX)/indocyanine green (ICG) was designed for effective photothermal/chemotherapy combination therapy. The anticancer drug DOX was anchored to the polymer on the surface of MSN by reversible covalent bond cis-aconitic anhydride with a drug loading of 10%. Meanwhile, the small-molecule dye was loaded into the pores of MSN, and PTT mediated by near-infrared (NIR) radiation could further kill cancer cells. Under low-pH stimulation, the cis-aconitic anhydride bond breaks and DOX is released, with a 65% increase in cumulative drug release over 50 h compared to that at pH 7.4 (normal physiological environment). The high temperature induced by photothermal conversion accelerated the reversible covalent bond breakage, and the cumulative drug release at pH 5.0 for 3 h at elevated temperature up to 50 °C increased by 24.3% compared with that under normal physiological conditions (T = 37 °C), demonstrating that increasing the temperature can reduce the time required to reach blood drug concentration. In vitro cytotoxicity results revealed that the prodrug delivery system showed stronger cytotoxicity under NIR light irradiation compared with free DOX, with more than 90% of tumor cells killed after 48 h. Therefore, MSN@poly(PEGMA-co-HEMA-g-DOX)/ICG enhanced the synergistic effect of chemotherapy through photothermal action and accelerated reversible chemical bond cleavage, which has great potential in the combined therapy of cancer.

Self-assembly of cyclic grafted copolymers with rigid rings and their potential as drug nanocarriers.

Enhancing the performance of polymer micelles by purposeful regulation of their structures is a challenging topic that receives widespread attention. In this study, we systematically conduct a comparative study between cyclic grafted copolymers with rigid and flexible rings in the self-assembly behavior via dissipative particle dynamics (DPD) simulation. With a focus on the possible stacking ways of rigid rings, we propose the energy-driven packing mechanism of cyclic grafted copolymers with rigid rings. For cyclic grafted copolymers with large ring size (14 and 21-membered rings), rigid rings present a novel channel-layer-combination layout, which is determined by the balance between the potential energy of micelles (Emicelle) and the interaction energy between water and micelles (Eint). Based on this mechanism, we further regulate a series of complex self-assembling structures, including curved rod-like, T-shape, annular and helical micelles. Compared with flexible copolymers, cyclic grafted copolymers with rigid rings provide a larger and loose hydrophobic core and higher structural stability with micelles due to the unique packing way of rigid rings. Therefore, their micelles have a great potential as drug nanocarriers. They possess a better drug loading capacity and disassemble more quickly than flexible counterparts under acidic tumor microenvironment. Furthermore, the endocytosis kinetics of rigid micelles is faster than the flexible counterparts for the adsorption and wrapping process. This study may provide a reasonable idea of structural design for polymer micelles to enhance their performance in biomedical applications.

[Advances in enrichment of phosphorylated peptides and glycopeptides by smart polymer-based materials].

Protein post-translational modification (PTM) is at the forefront of focus of proteomics research. It not only regulates protein folding, state, activity, localization, and protein interactions, but also helps scientists understand the biological processes of organisms more comprehensively, providing stronger support and basis for the prediction, diagnosis, and treatment of diseases. In living organisms, there are more than 300 types of PTMs of proteins and their modification processes are dynamic. At the same time, protein modifications do not exist in isolation. The occurrence of the same physiological or pathological process requires the joint action of various modified proteins, which affect and coordinate with each other. Owing to the low abundance of PTM products (e. g., phosphorylated peptides or glycopeptides) and the presence of strong background interference, it is difficult to analyze them directly through mass spectrometry. Therefore, the development efficient materials and techniques for the selective enrichment of PTM peptides is urgently needed. Conventional separation methods have partially solved the challenges involved in the enrichment of glycopeptides and phosphorylated peptides; however, there are some inevitable issues, such as the excessive binding force of metal ions (e. g., Fe3+and Ti4+) toward multiple phosphorylated peptides, resulting in difficulty in elution and identification through mass spectrometry. In addition, owing to the insufficient binding affinity of materials toward glycopeptides, most glycopeptides that have been identified at present are of the sialic acid type, and a large number of neutral glycans, for instance, O-link glycopeptides and high mannose-type glycans are difficult to enrich and identify.The emergence of smart polymers provides a new avenue for the development of PTM-enriched materials. Several studies have reported that smart polymers can reversibly change their structure and function through external physical, chemical, or biological stimulation, to achieve highly controllable adsorption and desorption of phosphorylated peptides and glycopeptides. Based on this strategy, a series of novel enrichment materials and methods have been developed, which have greatly attracted the interest of researchers. On the one hand, the response changes of smart polymers include the increase or decrease of hydrophobicity, the change of shape and morphology, the redistribution of surface charge, the exposure or hiding of affinity ligands, etc. Changes in these properties can be achieved by simply changing external conditions such as temperature, pH, solvent polarity, and biomolecules. These properties, in turn, enable the fine-tuning of the affinity between the target and the smart polymers. Furthermore, the affinity can provide an additional driving force, which can significantly improve biological separation.On the other hand, smart polymers provide a series of convenient and expandable platforms for integrating various functional modules, such as specific recognition components, which will facilitate the development of novel enrichment materials for protein methylation, acetylation, and ubiquitination. Smart polymer materials show great potential in the field of separation, which is promising for the analysis and research of protein PTMs. This review summarizes the research progress of smart polymer materials for the separation and enrichment of phosphorylated peptides and glycopeptides according to nearly 50 representative articles from the Web of Science in the past two decades.