Characterization of a multi-domain exo-ß-1,3-galactanase from Paenibacillus xylanexedens.

ß-1,3-Galactanases selectively degrade ß-1,3-galactan, thus it is an attractive enzyme technique to map high-galactan structure and prepare galactooligosaccharides. In this work, a gene encoding exo-ß-1,3-galactanase (PxGal43) was screened form Paenibacillus xylanexedens, consisting of a GH43 domain, a CBM32 domain and α-L-arabinofuranosidase B (AbfB) domain. Using ß-1,3-galactan (AG-II-P) as substrate, the recombined enzyme expressed in Escherichia coli BL21 (DE3) exhibited an optimal activity at pH 7.0 and 30 °C. The enzyme was thermostable, retaining >70 % activity after incubating at 50 °C for 2 h. In addition, it showed high tolerance to various metal ions, denaturants and detergents. Substrate specificity indicated that PxGal43 hydrolysis only ß-1,3-linked galactosyl oligosaccharides and polysaccharides, releasing galactose as an exo-acting manner. The function of the CBM32 and AbfB domain was revealed by their sequential deletion and suggested that their connection to the catalytic domain was crucial for the oligomerization, catalytic activity, substrate binding and thermal stability of PxGal43. The substrate docking and site-directed mutagenesis proposed that Glu191, Gln244, Asp138 and Glu81 served as the catalytic acid, catalytic base, pKa modulator, and substrate identifier in PxGal43, respectively. These results provide a better understanding and optimization of multi-domain bacterial GH43 ß-1,3-galactanase for the degradation of arabinogalactan.

Nickel-Catalyzed Deaminative Alkyl-Alkyl Cross-Coupling of Katritzky Salts with Cyclopropanols: Merging C-N and C-C Bond Activation.

Herein, we report a general and practical nickel-catalyzed deaminative alkylation of Katritzky salts with cyclopropyl alcohols via merging C-N and C-C bond activation. This protocol enables the formation of an alkyl-alkyl bond along with the generation of a versatile ketone functional group in a single operation, thus providing a convenient approach for accessing ß-alkyl ketones. This reaction is distinguished by its high functional group tolerance, broad substrate scope, and efficient late-stage derivatization of complex bioactive molecules.

Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway.

In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C( KIF2C ) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2C gene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2C gene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2C gene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2C was highly expressed in HCC cells. KIF2C silencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2C silencing enhanced the sensitivity of HCC cells to cisplatin. KIF2C silencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2C silencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2C shows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

Environment-Interactive Programmable Deformation of Electronically Innervated Synergistic Fluorescence-Color/Shape Changeable Hydrogel Actuators.

Utilization of life-like hydrogels to replicate synergistic shape/color changeable behaviors of living organisms has been long envisaged to produce robust functional integrated soft actuators/robots. However, it remains challenging to construct such hydrogel systems with integrated functionality of remote, localized and environment-interactive control over synergistic discoloration/actuation. Herein, inspired by the evolution-optimized bioelectricity stimulus and multilayer structure of natural reptile skins, electronically innervated fluorescence-color switchable hydrogel actuating systems with bio-inspired multilayer structure comprising of responsive fluorescent hydrogel sheet and conductive Graphene/PDMS film with electrothermal effect is presented. Such rational structure enables remote control over synergistic fluorescence-color and shape changes of the systems via the cascading "electrical trigger-Joule heat generation-hydrogel shrinkage" mechanism. Consequently, local/sequential control of discoloration/actuation are achieved due to the highly controllable electrical stimulus in terms of amplitude and circuit design. Furthermore, by joint use with acoustic sensors, soft chameleon robots with unprecedented environment-interactive adaptation are demonstrated, which can intelligently sense environment signals to adjust their color/shape-changeable behaviors. This work opens previously unidentified avenues for functional integrated soft actuators/robots and will inspire life-like intelligent systems for versatile uses.

Light-Writing and Projecting Multicolor Fluorescent Hydrogels for On-Demand Information Display.

Intelligent rewritable display systems have been long expected to reduce the heavy consumption of single-use or transient devices in the age of Internet-of-Things. However, it remains challenging to construct such systems with integrated functionality of remote control, rapid activation, multicolor and multimode display. Herein, by learning from the unique multilayer arrangement of chromatophores in chameleon skins, a promising kind of rewritable hydrogel multicolor systems is presented that can combine the merits of near-infrared (NIR) light-writing and projecting modes for on-demand information display. Specifically, the systems have typical multilayer layout consisting of poly(dimethylsiloxane) (PDMS)-sealed carbon nanotubes (CNTs) film as photothermal control unit and embedded fluorescent hydrogels as multicolor display unit, in which thermoresponsive hydrogel is constrained within non-responsive hydrogel. Such rational structure design results in the establishment of one promising display mechanism via the cascading "light trigger-heat generation-fluorescence output" process. On this basis, rapid and reversible hand-written display of arbitrary information is achieved within 5 s. Also, sustainable light-projecting display of predesigned multicolor patterns is demonstrated due to the multilayer design that ensures easy patterning of photothermal control or hydrogel display layer. This study brings functional-integrated merits for novel rewritable display systems and open new possibility to construct high-end products for information display/transmission.

Organohydrogel Actuators with Adjustable Stimulus Responsiveness for On-Demand Morphing.

Hydrogel actuators showing shape morphing in response to external stimuli are of significant interest for their applications in soft robots, artificial muscles, etc. However, there is still a lack of hydrogel actuators with adjustable stimulus responsiveness for on-demand driving. In this study, an organohydrogel actuator was prepared by a two-step interpenetrating method, resulting in the coexistence of poly(N-isopropylacrylamide-co-4-(2-sulfoethyl)-1-(4-vinylbenzyl) pyridinium betaine) (p(NIPAM-SVBP)) hydrophilic networks and poly(lauryl methacrylate) (pLMA) hydrophobic networks with gradient distribution. In the initial state, the organohydrogel actuator can be driven globally under thermal stimulation. Owing to the unique alkali-chromic performance of SVBP, the organohydrogel actuator can be endowed with photothermal properties and actuate locally under the stimulus of NIR light. More importantly, the organohydrogel will return to the original colorless state after being treated with acid solution. Our work provides a new insight into designing and fabricating novel actuators with adjustable stimulus responsiveness for on-demand morphing.

Bio-Inspired Electro-Thermal-Hygro Responsive Rewritable Systems with Temporal/Spatial Control for Environment-Interactive Information Display.

Utilization of rewritable luminescent materials for secure information storage and delivery has long been envisaged to reduce the cost and environmental wastes. However, it remains challenging to realize a temporally/spatially controlled display of the written information, which is crucial for secure information encryption. Here, inspired by bioelectricity-triggered skin pattern switching in cephalopods, an ideal rewritable system consisting of conductive graphene film and carbon dots (CDs) gel with blue-to-red fluorescence-color changes via water-triggered CDs aggregation and re-dispersion is presented. Its rewritability is guaranteed by using water ink to write on the CDs-gel and employing Joule heat of graphene film to evaporate water. Due to the highly controlled electrical stimulus, temporally/spatially controlled display is achieved, enabling on-demand delivery and duration time regulation of the written information. Furthermore, new-concept environment-interactive rewritable system is obtained by integrating sensitive acoustic/optical sensors and multichannel electronic time-delay devices. This work opens unprecedented avenues of rewritable systems and expands potential uses for information encryption/delivery.

Bio-inspired Structure-editing Fluorescent Hydrogel Actuators for Environment-interactive Information Encryption.

Many living organisms have the superb structure-editing capacity for better adaptation in dynamic environments over the course of their life cycle. However, it's still challenging to replicate such natural structure-editing capacity into artificial hydrogel actuating systems for enhancing environment-interactive functions. Herein, we learn from the metamorphosis development of glowing octopus to construct proof-of-concept fluorescent hydrogel actuators with life-like structure-editing capacity by developing a universal stepwise inside-out growth strategy. These actuators could perform origami-like 3D shape deformation and also enable the postnatal growth of new structures to adapt additional actuating states for different visual information delivery by using different environment keys (e.g., temperature, pH). This study opens previously unidentified-avenues of bio-inspired hydrogel actuators/robotics and extends the potential uses for environment-interactive information encryption.

A Multiparametric MRI-Based Radiomics Nomogram for Preoperative Prediction of Survival Stratification in Glioblastoma Patients With Standard Treatment.

OBJECTIVE: To construct and validate a radiomics nomogram for preoperative prediction of survival stratification in glioblastoma (GBM) patients with standard treatment according to radiomics features extracted from multiparameter magnetic resonance imaging (MRI), which could facilitate clinical decision-making. METHODS: A total of 125 eligible GBM patients (53 in the short and 72 in the long survival group, separated by an overall survival of 12 months) were randomly divided into a training cohort (n = 87) and a validation cohort (n = 38). Radiomics features were extracted from the MRI of each patient. The T-test and the least absolute shrinkage and selection operator algorithm (LASSO) were used for feature selection. Next, three feature classifier models were established based on the selected features and evaluated by the area under curve (AUC). A radiomics score (Radscore) was then constructed by these features for each patient. Combined with clinical features, a radiomics nomogram was constructed with independent risk factors selected by the logistic regression model. The performance of the nomogram was assessed by AUC, calibration, discrimination, and clinical usefulness. RESULTS: There were 5,216 radiomics features extracted from each patient, and 5,060 of them were stable features judged by the intraclass correlation coefficients (ICCs). 21 features were included in the construction of the radiomics score. Of three feature classifier models, support vector machines (SVM) had the best classification effect. The radiomics nomogram was constructed in the training cohort and exhibited promising calibration and discrimination with AUCs of 0.877 and 0.919 in the training and validation cohorts, respectively. The favorable decision curve analysis (DCA) indicated the clinical usefulness of the radiomics nomogram. CONCLUSIONS: The presented radiomics nomogram, as a non-invasive tool, achieved satisfactory preoperative prediction of the individualized survival stratification of GBM patients.

Supramolecular Assembly of Shape Memory and Actuating Hydrogels for Programmable Shape Transformation.

The deformable diversity of organisms in nature has inspired the development of bionic hydrogel actuators. However, the anisotropic structures of hydrogel actuators cannot be altered after the fabrication process, which restricts hydrogel actuators to provide complex and diverse shape deformations. Herein, we propose a dual programming method to generate numerous anisotropic structures from initial isotropic gelatin-containing hydrogels; the isotropic hydrogel blocks could be first assembled into anisotropic structures based on the coil-triple helix transition of gelatin, and then, the assembled hydrogels could further be fixed into various temporary anisotropies, so that they can produce complex and diverse deformations under the stimulation of pH. In addition, the shape programming and deformation behaviors are reversible. This dual programming method provides more potential for the application of hydrogel actuators in soft robots and bionics.

Cephalopod-Inspired Design of Photomechanically Modulated Display Systems for On-Demand Fluorescent Patterning.

Cephalopods can display variable body color/patterns upon environmental stimulation via bioelectricity-controlled muscle contraction/expansion of skin chromatophores. However, it remains challenging to produce artificial display analogs that exhibit reversible and rapid switching between multiple expected luminescent patterns, although such systems are very appealing for many practical uses (e.g., data encryption). Inspired by the bioelectromechanical display tactic of cephalopods, in this work, a conceptually new photomechanically modulated fluorescent system that enables on-demand display of fluorescent patterns via a cascading stimulation-mechanical movement-optical output conduction mechanism is presented. Specifically, this biomimetic system comprises a customizable hollow display panel and a bottom-tethered photothermally responsive fluorescent actuator. Under NIR light, the photomechanically bending movements of the fluorescent actuator will immediately cover the hollow window of the display panel and synchronously manifest as the display of fluorescent patterns. Owing to its desirable time- and light-power-dependent actuating behaviors, diverse fluorescent patterns/information can be dynamically and reversibly displayed by facilely controlling this single remote NIR signal. This bioinspired strategy is universal and promising for fabricating on-demand fluorescent display platforms that combine a wide choice of fluorophores, remote control with high spatial/temporal precision, and especially single-input multiple-output features.

Aggregation-Induced Emissive Carbon Dots Gels for Octopus-Inspired Shape/Color Synergistically Adjustable Actuators.

Some living organisms such as the octopus have fantastic abilities to simultaneously swim away and alter body color/morphology for disguise and self-protection, especially when there is a threat perception. However, it is still quite challenging to construct artificial soft actuators with octopus-like synergistic shape/color change and directional locomotion behaviors, but such systems could enhance the functions of soft robotics dramatically. Herein, we proposed to utilize unique hydrophobic carbon dots (CDs) with rotatable surficial groups to construct the aggregation-induced emission (AIE) active glycol CDs polymer gel, which could be further employed to be interfacially bonded to an elastomer to produce anisotropic bilayer soft actuator. When putting the actuator on a water surface, glycol spontaneously diffused out from the gel layer to allow water intake, resulting in a color change from a blue dispersion fluorescence to red AIE and a shape deformation, as well as a large surface tension gradient that can promote its autonomous locomotion. Based on these findings, artificial soft swimming robots with octopus-like synergistic shape/color change and directional swimming motion were demonstrated. This study provides an elegant strategy to develop advanced multi-functional bio-inspired intelligent soft robotics.

Promotion of Color-Changing Luminescent Hydrogels from Thermo to Electrical Responsiveness toward Biomimetic Skin Applications.

The active color-changing ability of many living species has inspired scientists to replicate the optical property into soft wet and tissue-like hydrogel materials. However, the color-changing processes of most reported examples are controlled by the traditional stimuli (e.g., pH, temperature, and ions), which may suffer from the residual chemical product accumulation, and have difficulty in achieving local control and integration into the commercial robots, especially when applied as biomimetic skins. Herein, inspired by the nervous (bioelectricity) control of skin color change in cephalopods, we present an electrically powered multicolor fluorescent hydrogel system with asymmetric configuration that couples thermoresponsive fluorescent hydrogel with stacked graphene assembly (SGA)-based conductive paper through luminous paint as the middle layer. Owing to the highly controllable electrical stimulus in terms of amplitude and duration, the Joule heat supplied by SGA film can be regulated locally and in real time, leading to precise and local emission color control at low voltage. It also avoids the addition of any chemicals. Furthermore, the electrically powered color-changing hydrogel system can be conveniently integrated into the commercial robots as biomimetic skins that help them achieve desirable camouflage, display, or alarming functions.

Preoperative Prediction of Meningioma Consistency via Machine Learning-Based Radiomics.

OBJECTIVES: The aim of this study was to establish and validate a radiomics nomogram for predicting meningiomas consistency, which could facilitate individualized operation schemes-making. METHODS: A total of 172 patients was enrolled in the study (train cohort: 120 cases, test cohort: 52 cases). Tumor consistency was classified as soft or firm according to Zada's consistency grading system. Radiomics features were extracted from multiparametric MRI. Variance selection and LASSO regression were used for feature selection. Then, radiomics models were constructed by five classifiers, and the area under curve (AUC) was used to evaluate the performance of each classifiers. A radiomics nomogram was developed using the best classifier. The performance of this nomogram was assessed by AUC, calibration and discrimination. RESULTS: A total of 3840 radiomics features were extracted from each patient, of which 3719 radiomics features were stable features. 28 features were selected to construct the radiomics nomogram. Logistic regression classifier had the highest prediction efficacy. Radiomics nomogram was constructed using logistic regression in the train cohort. The nomogram showed a good sensitivity and specificity with AUCs of 0.861 and 0.960 in train and test cohorts, respectively. Moreover, the calibration graph of the nomogram showed a favorable calibration in both train and test cohorts. CONCLUSIONS: The presented radiomics nomogram, as a non-invasive prediction tool, could predict meningiomas consistency preoperatively with favorable accuracy, and facilitated the determination of individualized operation schemes.

Multicolor Fluorescent Polymeric Hydrogels.

Multicolor fluorescent polymeric hydrogels (MFPHs) are three-dimensionally crosslinked hydrophilic polymer networks with tunable emission color. Different from the classic fluorescent materials that are used primarily in dry solid states or solutions, MFPHs exist as highly water-swollen quasi-solids. They thus present many promising properties of both solids and solution, including tissue-like mechanical properties, an intrinsic soft and wet nature, fabulous biocompatibility, along with a responsive volume, shape, and fluorescence color change. These advantageous properties hold great potential in many applications such as sensing, bioimaging, information encoding, encryption, biomimetic actuators, and soft robotics. This Review gives an in-depth overview of recent progress in the field of MFPHs, with a particular focus on the diverse construction methods and important demonstrated applications. Current challenges and future perspectives on MFPHs are also discussed.

Naphthalimide-Based Aggregation-Induced Emissive Polymeric Hydrogels for Fluorescent Pattern Switch and Biomimetic Actuators.

Substituted naphthalimide (NI) moieties are highly versatile and newly recognized aggregation-induced emission (AIE) building blocks for many potentially useful smart molecules, polymers, and nanoparticles. However, the introduction of NI fluorophore into cross-linked polymeric networks to prepare AIE-active hydrogels still remains underdeveloped. Herein, a novel naphthalimide-based aggregation-induced emissive polymeric hydrogel is reported, followed by its proof-of-concept applications as fluorescence pattern switch and biomimetic actuator. The hydrogel, bearing semi-interpenetrating polymer networks, is synthesized starting from N-isopropylacrylamide, hydroxyethyl methacrylate, and a newly designed NI monomer (4-phenoxy-N-allyl-1,8-naphthalimide, PhAN). Rational molecular design for AIE-active PhAN monomer lies in modification of the NI core with rigid and bulky phenoxy group to break its planarity to produce desirable propeller-shaped molecular conformation. The as-prepared hydrogel is proved to be a aggregation-induced blue-light-emitting hydrogel. It also shows volume phase transition behavior and is endowed with thermally responsive synergistic emission and transmittance change, thus enabling simultaneous regulation of two optical properties merely by one single stimulus. These useful advantages further encourage fabrication of several proto-type fluorescence pattern switching and biomimetic actuating devices. This study may not only enlarge the list of fluorescent hydrogels but also serve as a novel smart optical platform for potential anticounterfeiting, sensing, displaying, or actuating applications.

Supramolecular Fabrication of Complex 3D Hollow Polymeric Hydrogels with Shape and Function Diversity.

Inspired by the high importance of hollow structures in nature such as blood vessels and bamboos in matter transportation, properties enhancement, or even survival of living creatures, the creation of hollow materials remains of considerable interest. However, constructing hollow unique living-like soft and wet polymeric hydrogels with desirable structures and functionalities is still a big challenge. Here, we reported a robust and effective strategy to fabricate complex three-dimensional (3D) hollow polymeric hydrogel with designed shape and function diversity on the basis of supramolecular interactions. By placing a Ca2+ included gelatin core into the solution of alginate, hydrogel shell could be formed along with the shape of the gelatin core via coordination between alginate chains and Ca2+ diffused from gelatin. The hollow hydrogel could finally be obtained by dissolving the gelatin core. Various complex 3D hollow structures could be achieved by designing/constructing assembled gelatin core as a building block with adjustable supramolecular metal coordination position and strength. Moreover, hollow hydrogels with function diversity could be developed by introducing functional polymers or nanoparticles into the hydrogel wall. This work has made important progress in developing hollow polymeric hydrogel with desirable structures, shapes, and various functional applications including soft actuators and chemical reaction containers.

Bioinspired Synergistic Fluorescence-Color-Switchable Polymeric Hydrogel Actuators.

Many living organisms have amazing control over their color, shape, and morphology for camouflage, communication, and even reproduction in response to interplay between environmental stimuli. Such interesting phenomena inspire scientists to develop smart soft actuators/robotics via integrating color-changing functionality based on polymer films or elastomers. However, there has been no significant progress in synergistic color-changing and shape-morphing capabilities of life-like material systems such as hydrogels. Herein, we reported a new class of bioinspired synergistic fluorescence-color-switchable polymeric hydrogel actuators based on supramolecular dynamic metal-ligand coordination. Artificial hydrogel apricot flowers and chameleons have been fabricated for the first time, in which simultaneous color-changing and shape-morphing behaviors are controlled by the subtle interplay between acidity/alkalinity, metal ions, and temperature. This work has made color-changeable soft machines accessible and is expected to hold wide potential applications in biomimetic soft robotics, biological sensors, and camouflage.

miR-486 inhibited osteosarcoma cells invasion and epithelial-mesenchymal transition by targeting PIM1.

OBJECTIVE: Osteosarcoma is the most common malignant tumor of bone with high recurrent rate. miR-486 was downregulated and acted as a tumor suppressor in plenty of tumors. The purpose of this study was to explore how miR-486 worked in osteosarcoma on cell invasion and EMT. RESULTS: miR-486 was low expressed in osteosarcoma while PIM1 was overexpressed, and it had negative correlation between miR-486 and PIM1. miR-486 upregulation or PIM1 downregulation could inhibit osteosarcoma cell invasion and EMT. Meanwhile, miR-486 mediated PIM1 expression through binding to PIM1 mRNA 3'-UTR. PIM1 could reveal partial function of miR-486 on osteosarcoma invasion. In addition, miR-486 low expression or PIM1 overexpression predicted poor prognosis of osteosarcoma patients. CONCLUSION: miR-486 regulated osteosarcoma cell invasion and EMT through targeting to PIM1. miR-486 low expression or PIM1 overexpression predicted poor prognosis of osteosarcoma patients. The newly identified miR-486/PIM1 axis provides novel insight into the pathogenesis of osteosarcoma.

Protein-Based 3D Microstructures with Controllable Morphology and pH-Responsive Properties.

The microtechnology of controlling stimuli-responsive biomaterials at micrometer scale is crucial for biomedical applications. Here, we report bovine serum albumin (BSA)-based three-dimensional (3D) microstructures with tunable surface morphology and pH-responsive properties via two-photon polymerization microfabrication technology. The laser processing parameters, including laser power, scanning speed, and layer distance, are optimized for the fabrication of well-defined 3D BSA microstructures. The tunable morphology of BSA microstructures and a wide range of pH response corresponding to the swelling ratio of 1.08-2.71 have been achieved. The swelling behavior of the microstructures can be strongly influenced by the concentration of BSA precursor, which has been illustrated by a reasonable mechanism. A panda face-shaped BSA microrelief with reversible pH-responsive properties is fabricated and exhibits unique "facial expression" variations in pH cycle. We further design a mesh sieve-shaped microstructure as a functional device for promising microparticle separation. The pore sizes of microstructures can be tuned by changing the pH values. Therefore, such protein-based microstructures with controllable morphology and pH-responsive properties have potential applications especially in biomedicine and biosensors.