Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

Bioinspired adhesive hydrogel based on serotonin-modified gelatin and oxidized hyaluronic acid for rapid hemostasis and wound healing.

A hybrid hydrogel system (GSOHA) consisting of serotonin-grafted gelatin and oxidized hyaluronic acid (OHA) was developed in this study to efficiently control bleeding and prevent bacterial infections during surgery and trauma. The study results showed that the incorporation of serotonin successfully produced hydrogels with rapid hemostatic, antibacterial, and antioxidant properties. The GSOHA hydrogel exhibited considerably stronger tissue adhesion (15.55 ± 0.36 kPa) to porcine skin than the commercial fibrin glue (1.09 ± 0.04 kPa). In addition, the hydrogel could rapidly absorb blood cells and stimulate cell conjugation with serotonin addition. In vitro experiments using endothelial cells and erythrocytes demonstrated the excellent biocompatibility and hemocompatibility of the hydrogel. Most importantly, the GSOHA hydrogel accelerated the wound healing process in a full-thickness skin defect mice model, and the histological staining results demonstrated that GSOHA significantly promoted collagen deposition and vascularization. In conclusion, this study demonstrated the significant potential of the GSOHA hydrogel as an adhesive dressing for rapid hemostasis and wound healing.

Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo.

Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through 3D and spatiotemporal changes in vivo. The matrix stiffness is a crucial factor during bone tissue development. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, a dynamic and controllable stiffening 3D biomimetic model is created to regulate the osteogenic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. The findings show that these dynamic hydrogels allowed cells to spread and expand prior to the secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, present significantly elevated osteogenic ECM secretion, gene expression, and nuclear localization of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). In vivo evaluation of animal experiments further indicates that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promotes bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo.

Hydrophobically modified hydrogel with enhanced tissue adhesion and antibacterial capacity for wound healing.

The increasing emergence of drug-resistant bacteria and bacteria-infected wounds highlights the urgent need for new kinds of antibacterial wound dressing. Herein, we reported a novel bio-adhesive and antibacterial hydrogel consisting of hydrophobically modified gelatin, oxidized konjac glucomannan, and dopamine. This kind of functional hydrogel was endowed with developed stability in a liquid environment and strong tissue adhesion, even much higher than the commercial fibrin glue to wounds. The excellent bacteria-killing efficiency of hydrophobically modified hydrogel against S. aureus and E. coli was verified, as well as the low hemolysis ratio against erythrocytes in vitro. The hydrogel also exhibited good cytocompatibility in terms of supporting cell proliferation. Most importantly, these abovementioned properties could be customized by altering the substitution degree of hydrophobic groups during manufacturing, demonstrating its great potential in biomedical fields such as tissue adhesive and wound dressing.

Protocatechualdehyde-ferric iron tricomplex embedded gelatin hydrogel with adhesive, antioxidant and photothermal antibacterial capacities for infected wound healing promotion.

Because of the indiscriminate use of antibiotics and the increasing threat of drug-resist bacteria, there is an urgent need to develop novel antibacterial strategies to combat infected wounds. In this work, stable tricomplex molecules (PA@Fe) assembled by protocatechualdehyde (PA) and ferric iron (Fe) were successfully synthesized and then embedded in the gelatin matrix to obtain a series of Gel-PA@Fe hydrogels. The embedded PA@Fe served as a crosslinker to improve the mechanical, adhesive and antioxidant properties of hydrogels through coordination bonds (catechol-Fe) and dynamic Schiff base bonds, meanwhile acting as a photothermal agent to convert near-infrared (NIR) light into heat to kill bacteria effectively. Importantly, in vivo evaluation through an infected full-thickness skin wound mice model revealed that Gel-PA@Fe hydrogel developed collagen deposition, and accelerated reconstruction of wound closure, indicating great potential of Gel-PA@Fe hydrogel in promoting the healing process of infected full-thickness wounds.

Hydrogel coating based on dopamine-modified hyaluronic acid and gelatin with spatiotemporal drug release capacity for quick endothelialization and long-term anticoagulation.

Due to the vital roles of vascular intima in preventing thrombus generation and maintaining vascular patency, methods to promote quick endothelialization on vascular grafts have drawn much attention. In this study, we novelly applied a double-layered hydrogel coating with spatiotemporal drug release capacity on a polycaprolactone (PCL) fibrous scaffold. The composite coating consisted of an inner dopamine-modified hyaluronic acid (HA) hydrogel and an outer gelatin hydrogel, which were generated via different crosslinking methods. Especially, heparin and chondroitin sulfate were introduced to the HA and gelatin hydrogels during the processing, thus endowing the vascular scaffold spatiotemporal drug release behavior. The composite coating developed surface hydrophilicity and mechanical properties of the PCL scaffold meanwhile stimulating the proliferation and angiogenesis behaviors of endothelial cells. Long-term anticoagulation property of the modified scaffold was also demonstrated in vitro. This investigation provides a universal strategy for quick endothelialization and long-term anticoagulation promotion of vascular grafts, which may be potentially used in treating cardiovascular diseases.

Surface modification with hydrophilic and heparin-loaded coating for endothelialization and anticoagulation promotion of vascular scaffold.

Surface modifications are common approaches to promote endothelialization and resist thrombus, therefore obtaining long-term patency of vascular grafts. Herein, we developed a functional coating based on hyaluronic acid (HA), dopamine (DA), and heparin. In the present study, dopamine was firstly grafted to the HA molecules. The DA-grafted HA material was then applied to the surface of fibrous PCL scaffold via oxidation polymerization. Heparin was directly loaded during the coating, instead of grafting. The composite coating enhanced the surface hydrophilicity of PCL scaffold, as well as the mechanical properties. Notably, the coated scaffold could promote EC proliferation and angiogenesis behavior via the upregulation of CD31 gene expression regardless of heparin addition. It also showed more effective inhibition of platelet adhesion and blood clotting in vitro. These results lead us to the conclusion that this functional coating is great potential in treating cardiovascular diseases in terms of promoting endothelialization, reducing thrombus, and maintaining the long-term patency of vascular grafts.

MRF-IUNet: A Multiresolution Fusion Brain Tumor Segmentation Network Based on Improved Inception U-Net.

The automatic segmentation method of MRI brain tumors uses computer technology to segment and label tumor areas and normal tissues, which plays an important role in assisting doctors in the clinical diagnosis and treatment of brain tumors. This paper proposed a multiresolution fusion MRI brain tumor segmentation algorithm based on improved inception U-Net named MRF-IUNet (multiresolution fusion inception U-Net). By replacing the original convolution modules in U-Net with the inception modules, the width and depth of the network are increased. The inception module connects convolution kernels of different sizes in parallel to obtain receptive fields of different sizes, which can extract features of different scales. In order to reduce the loss of detailed information during the downsampling process, atrous convolutions are introduced in the inception module to expand the receptive field. The multiresolution feature fusion modules are connected between the encoder and decoder of the proposed network to fuse the semantic features learned by the deeper layers and the spatial detail features learned by the early layers, which improves the recognition and segmentation of local detail features by the network and effectively improves the segmentation accuracy. The experimental results on the BraTS (the Multimodal Brain Tumor Segmentation Challenge) dataset show that the Dice similarity coefficient (DSC) obtained by the method in this paper is 0.94 for the enhanced tumor area, 0.83 for the whole tumor area, and 0.93 for the tumor core area. The segmentation accuracy has been improved.

Functional Hydrogels with Chondroitin Sulfate Release Properties Regulate the Angiogenesis Behaviors of Endothelial Cells.

Functional hydrogels with properties that mimic the structure of extracellular matrix (ECM) and regulate cell behaviors have drawn much attention in biomedical applications. Herein, gelatin-based hydrogels were designed and loaded with chondroitin sulfate (CS) to endow biological regulation on the angiogenesis behaviors of endothelial cells (ECs). Manufactured hydrogels containing various amounts of CS were characterized via methods including mechanical tests, cytocompatibility, hemolysis, and angiogenesis assays. The results showed that the prepared hydrogels exhibited excellent mechanical stability, cytocompatibility, and hemocompatibility. Additionally, the angiogenesis behaviors of ECs were obviously promoted. However, excessive loading of CS would weaken the effect due to a higher proportion of occupation on the cell membrane. In conclusion, this investigation highlights the great potential of these hydrogels in treating ischemic diseases and accelerating tissue regeneration in terms of regulating the angiogenesis process via CS release.

In situ forming hydrogel recombination with tissue adhesion and antibacterial property for tissue adhesive.

In situ forming hydrogels with strong adhesive strength and antibacterial activity are of great interest to serve as tissue adhesive in fields like wound dressing and mass hemorrhage. In this study, hybrid hydrogel (GOHA) based on gelatin and oxidized hyaluronic acid was developed and endowed with excellent mechanical strength and tissue adhesion. According to our results, GOHA hydrogel exhibits a fast gelation time of around 60 s, robust compression strength of 223.43 ± 24.28 kPa, and strong adhesion of 14.33 ± 0.78 kPa to porcine skin, which is much higher than that of commercial fibrin glue (around 1.00 kPa). Meanwhile, through the loading of levofloxacin, obvious antibacterial activity can be obtained for wider applications. Notably, it would not compromise the hemocompatibility and cytocompatibility in vitro. In summary, this kind of hybrid hydrogel shows great potential as tissue adhesive in biomedical fields.

Petal development and elaboration.

Petals can be simple or elaborate, depending on whether they have complex basic structures and/or highly specialized epidermal modifications. It has been proposed that the independent origin and diversification of elaborate petals have promoted plant-animal interactions and, therefore, the evolutionary radiation of corresponding plant groups. Recent advances in floral development and evolution have greatly improved our understanding of the processes, patterns, and mechanisms underlying petal elaboration. In this review, we compare the developmental processes of simple and elaborate petals, concluding that elaborate petals can be achieved through four main paths of modifications (i.e. marginal elaboration, ventral elaboration, dorsal elaboration, and surface elaboration). Although different types of elaborate petals were formed through different types of modifications, they are all results of changes in the expression patterns of genes involved in organ polarity establishment and/or the proliferation, expansion, and differentiation of cells. The deployment of existing genetic materials to perform a new function was also shown to be a key to making elaborate petals during evolution.

Multi-Crosslinked Hydrogels with Instant Self-Healing and Tissue Adhesive Properties for Biomedical Applications.

Due to the defects like long gelling time, inferior mechanical properties and weak adhesion, in situ forming hydrogels are still restricted in biomedical applications like viscera rupture and targeted therapy. To address these problems, a new kind of multi-crosslinked hydrogel (G-OKG-DA) consisting of gelatin, oxidized konjac glucomannan (OKG), and dopamine (DA) is proposed in this study. The resulting hybrid hydrogel is endowed with a short gelling time (≈3 min) and injectable capacity. According to the mechanical and adhesive tests, G-OKG-DA hydrogel shows a robust tensile strength of 23.94 kPa, as well as a higher adhesive strength (≈150 kPa) than commercial fibrin glue. In addition, an instant self-healing behavior of G-OKG-DA hydrogel can be found, which is attributed to multi-cross-linking reactions including Schiff-based dynamic covalent bonds between OKG and gelatin, oxidative polymerization of DA, and catechol-mediated chemistry like Michael addition and DA-quinone coupling. Importantly, the multi-crosslinked hydrogel will not compromise its hemocompatibility and cytocompatibility in vitro, suggesting potential applications in biomedical fields as tissue adhesive and implants.

Endothelial Cell Migration Regulated by Surface Topography of Poly(ε-caprolactone) Nanofibers.

The study of cell migration on biomaterials is of great significance in tissue engineering and regenerative medicine. In recent years, there has been increasing evidence that the physical properties of the extracellular matrix (ECM), such as surface topography, affect various cellular behaviors such as proliferation, adhesion, and migration. However, the biological mechanism of surface topography influencing cellular behavior is still unclear. In this study, we prepared polycaprolactone (PCL) fibrous materials with different surface microstructures by solvent casting, electrospinning, and self-induced crystallization. The corresponding topographical structure obtained is a two-dimensional (2D) flat surface, 2.5-dimensional (2.5D) fibers, and three-dimensional (3D) fibers with a multilevel microstructure. We then investigated the effects of the complex topographical structure on endothelial cell migration. Our study demonstrates that cells can sense the changes of micro- and nanomorphology on the surface of materials, adapt to the physical environment through biochemical reactions, and regulate actin polymerization and directional migration through Rac1 and Cdc42. The cells on the nanofibers are elongated spindles, and the positive feedback of cell adhesion and actin polymerization along the fiber direction makes the plasma membrane continue to protrude, promoting cell polarization and directional migration. This study might provide new insights into the biomaterial design, especially those used for artificial vascular grafts.

Reduced graphene oxide supported ZIF-67 derived CoP enables high-performance potassium ion storage.

Potassium-ion batteries (PIBs) are currently recognized as an emerging battery technology because of the rich resources and low cost of potassium. Nevertheless, investigations on exploiting suitable anode materials to meet stable potassium-ions storage remain to be a problem owing to the big radius size of potassium-ions. Herein, we designed N-doped carbon restricted CoP polyhedra embedded into reduced graphene oxide (rGO) sheet (CoP/NC@rGO) through coupling the function of ZIF-67 and rGO. For this composite, nano-scale CoP particles can be encapsulated by ZIF-67 derived carbon matrix, which significantly alleviates the volume change and promotes K+/e- transfer. Additionally, the combination of CoP/NC polyhedra and rGO nanosheets can build a fascinating 3D architecture to further improve the electronic conductivity of materials, as well as effectively preventing the aggregation of CoP/NC polyhedra. As a result, such composites can exhibit remarkable long-cycle performance, maintaining remarkable capacities of 177 mAh g-1 after 2800 cycles at 1 A g-1. This work provides a hopeful strategy that the combination of MOF-derived porous structures with rGO can effectively promote K+/e- transfer and improve the stability of electrode materials.

A High-Precision Automatic Pointer Meter Reading System in Low-Light Environment.

At present, pointer meters are still widely used because of their mechanical stability and electromagnetic immunity, and it is the main trend to use a computer vision-based automatic reading system to replace inefficient manual inspection. Many correction and recognition algorithms have been proposed for the problems of skew, distortion, and uneven illumination in the field-collected meter images. However, the current algorithms generally suffer from poor robustness, enormous training cost, inadequate compensation correction, and poor reading accuracy. This paper first designs a meter image skew-correction algorithm based on binary mask and improved Mask-RCNN for different types of pointer meters, which achieves high accuracy ellipse fitting and reduces the training cost by transfer learning. Furthermore, the low-light enhancement fusion algorithm based on improved Retinex and Fast Adaptive Bilateral Filtering (RBF) is proposed. Finally, the improved ResNet101 is proposed to extract needle features and perform directional regression to achieve fast and high-accuracy readings. The experimental results show that the proposed system in this paper has higher efficiency and better robustness in the image correction process in a complex environment and higher accuracy in the meter reading process.

Preparation of gelatin-based hydrogels with tunable mechanical properties and modulation on cell-matrix interactions.

Natural polymer material-based hydrogels normally show inferior mechanical stability and strength to bear large deformation and cyclic loading, therefore their applications in food, biomedical and tissue engineering fields are greatly limited. In this study, gelatin-based hydrogels with remarkable stability, as well as tunable mechanical properties, were prepared via a facile method known as the Hofmeister effect. The higher concentration of potassium sulfatesolution resulted in more dehydration and molecular chain folding, thus the treated hydrogels showed significantly improved tensile and compressive modulus, and decreased equilibrium swelling ratio, as revealed by scanning electron microscopy (SEM), Fourier transform infraredspectroscopy (FTIR), and mechanical tests, etc. Additionally, the reinforced hydrogels were recoverable and biocompatible to modulate the proliferation behavior of human umbilical vein endothelial cells. In conclusion, this paper provides a facile reference for tuning mechanical properties of gelatin-based hydrogels and cell-hydrogel interactions, which show potential capacity in tissue engineering and biomedical fields.

Gelatin/Oxidized Konjac Glucomannan Composite Hydrogels with High Resistance to Large Deformation for Tissue Engineering Applications.

In this study, gelatin hydrogels with remarkable compressive properties and recoverability were prepared via Shiff's base chemical cross-linking between gelatin and oxidized konjac glucomannan (OKG). The process of OKG was first optimized by adjusting parameters, that is, oxidation temperature and time during processing. Various percentages of obtained OKG (1, 2, 3, 4, and 5 wt % to gelatin) were introduced to make composite hydrogels (G-OKGs). These G-OKGs were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, swelling ratio, and mechanical tests. In comparison with pure gelatin hydrogels, the G-OKGs exhibit significantly increased stress and modulus, and favorable recoverability after cyclic large deformation (up to 85% of the original height). Additionally, G-OKGs with uniform porous structures are biocompatible to support the proliferation of human umbilical vein endothelial cells. In conclusion, this study provides a reference for developing mechanically stable and recoverable hydrogels, and these kinds of hydrogels show potential capacity in tissue engineering and biomedical applications that may be undergoing extra forces and large deformation.

Investigation on the tunable effect of oxidized konjac glucomannan with different molecular weight on gelatin-based composite hydrogels.

Herein, oxidized konjac glucomannan (OKG) with different molecular weight (Mw) were prepared as polysaccharide crosslinker to reinforce gelatin-based hydrogels. Then, properties of composite hydrogels with various OKGs were investigated via a series of methods, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), rheology, mechanical and biocompatibility tests. The results confirmed an increased degree of crosslinking and entanglement between gelatin and OKG with higher Mw. Besides, composite hydrogels not only showed increased mechanical strength, but self-healing ability at the same time, which were closely affected by the Mw of OKG. Furthermore, both composite hydrogels could support well proliferation of cells, which showed excellent capacity in tissue engineering and biomedical applications. In brief, this work provides a facile method to promote the overall properties of gelatin-based hydrogels, meanwhile revealed the relationship and mechanism underlying the effects of OKG with different Mw on composite hydrogels.

Stretchable Strain Sensor for Human Motion Monitoring Based on an Intertwined-Coil Configuration.

Wearable electronics, such as sensors, actuators, and supercapacitors, have attracted broad interest owing to their promising applications. Nevertheless, practical problems involving their sensitivity and stretchability remain as challenges. In this work, efforts were devoted to fabricating a highly stretchable and sensitive strain sensor based on dip-coating of graphene onto an electrospun thermoplastic polyurethane (TPU) nanofibrous membrane, followed by spinning of the TPU/graphene nanomembrane into an intertwined-coil configuration. Owing to the intertwined-coil configuration and the synergy of the two structures (nanoscale fiber gap and microscale twisting of the fiber gap), the conductive strain sensor showed a stretchability of 1100%. The self-inter-locking of the sensor prevents the coils from uncoiling. Thanks to the intertwined-coil configuration, most of the fibers were wrapped into the coils in the configuration, thus avoiding the falling off of graphene. This special configuration also endowed our strain sensor with an ability of recovery under a strain of 400%, which is higher than the stretching limit of knees and elbows in human motion. The strain sensor detected not only subtle movements (such as perceiving a pulse and identifying spoken words), but also large movements (such as recognizing the motion of fingers, wrists, knees, etc.), showing promising application potential to perform as flexible strain sensors.

Parallel evolution of apetalous lineages within the buttercup family (Ranunculaceae): outward expansion of AGAMOUS1, rather than disruption of APETALA3-3.

Complete loss of petals, or becoming apetalous, has occurred independently in many flowering plant lineages. However, the mechanisms underlying the parallel evolution of naturally occurring apetalous lineages remain largely unclear. Here, by sampling representatives of all nine apetalous genera/tribes of the family Ranunculaceae and conducting detailed morphological, expression, molecular evolutionary and functional studies, we investigate the mechanisms underlying parallel petal losses. We found that while non-expression/downregulation of the petal identity gene APETALA3-3 (AP3-3) is tightly associated with complete petal losses, disruptions of the AP3-3 orthologs were unlikely to be the real causes for the parallel evolution of apetalous lineages. We also found that, compared with their close petalous relatives, naturally occurring apetalous taxa usually bear slightly larger numbers of stamens, whereas the number of sepals remains largely unchanged, suggestive of petal-to-stamen rather than petal-to-sepal transformations. In addition, in the recently originated apetalous genus Enemion, the petal-to-stamen transformations have likely been caused by the mutations that led to the elevation and outward expansion of the expression of the C-function gene, AGAMOUS1 (AG1). Our results not only provide a general picture of parallel petal losses within the Ranunculaceae but also help understand the mechanisms underlying the independent originations of other apetalous lineages.