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Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation., Graphical abstract Image 1, Highlights • A novel aligned interpenetrating nanofiber hydrogel is first constructed for peripheral nerve regeneration. • The aligned hydrogel presents synergistic topographical and biochemical cues for peripheral nerve regeneration. • Nerve conduits filled with the aligned hydrogel can repair the long-distance sciatic nerve defects in 12 weeks. • The function recovery facilitated by the aligned hydrogel is comparable with that of autografts. • The aligned hydrogel upregulates regeneration-related genes and activates the PI3K/Akt and MAPK signaling pathways.

Due to high storage and calculation efficiency, hash-based methods have been widely used in image retrieval systems. Unsupervised deep hashing methods can learn the binary representations of images effectively without any annotations. The strategy of constraining hash code in the previous unsupervised methods may not fully utilize the structural information in semantic similarity. To address this problem, we propose a new strategy based on contrastive learning to capture high-level semantic similarity among features and preserve it in generated hash codes. In addition, we employ a novel framework to handle hash codes with different lengths simultaneously which is more time-saving in generating hash codes than existing methods. Extensive experiments on MIRFlickr, NUS-WIDE, and COCO benchmark datasets show that our method makes great improvement on the performance of unsupervised image retrieval.

To explore the regulation of keratinocyte growth factor (KGF) in the process of repairing rat skin wounds by taspine hydrochloride (TA/HCl), 45 male Sprague-Dawley (SD) rats were purchased and divided into an experimental group, a dimethyl sulfoxide (DMSO) control group, and a basic fibroblast growth factor (bFGF) control group, each with 15 only. A back trauma model was innovatively adopted to prevent rats from biting and contaminating. The wound healing time and healing rate of the rat, and the Hydroxyproline (Hyp) and KGF expressions were observed. Morphological changes of wound tissue and the number of capillaries were observed after hematoxylin-eosin (HE) staining. The results showed that wound healing rate of experimental group and bFGF group was significantly higher than that of DMSO group (P

Fibrous biotextiles are very popular structural forms that are widely used in medical products and devices ranging from sutures, bandages, wound dressing, and patches to all kinds of artificial grafts such as ligaments, tendons, blood vessels, heart valves, and tissue engineered scaffolds. Blow-spinning is a recently developed technique that enables the large-scale and efficient production of ultrathin fibers with diameters ranging from micrometer to nanometer. In this study, the blow-spinning process and parameters were optimized to steadily fabricate collagen nanofibers by ejecting a collagen solution with constant airflow with precisely controlled diameter and alignment. Different from the electrospun collagen nanofibrous membrane, the blow-spun one was fluffy and spongy with high porosity. It was observed that the blow-spun collagen membrane could better maintain the fiber structure after chemical crosslinking in comparison with the electrospun membrane crosslinked in the same condition, which probably attributed to the good porosity and permeability of crosslinking agent within the membranes. The

With the development of artificial intelligence, speech recognition and prediction have become one of the important research domains with wild applications, such as intelligent control, education, individual identification, and emotion analysis. Chinese poetry reading contains rich features of continuous pronunciations, such as mood, emotion, rhythm schemes, lyric reading, and artistic expression. Therefore, the prediction of the pronunciation characteristics of a Chinese poetry reading is the significance for the presentation of high-level machine intelligence and has the potential to create a high-level intelligent system for teaching children to read Tang poetry. Mel frequency cepstral coefficient (MFCC) is currently used to present important speech features. Due to the complexity and high degree of nonlinearity in poetry reading, however, there is a tough challenge facing accurate pronunciation feature prediction, that is, how to model complex spatial correlations and time dynamics, such as rhyme schemes. As for many current methods, they ignore the spatial and temporal characteristics in MFCC presentation. In addition, these methods are subjected to certain limitations on prediction for long-term performance. In order to solve these problems, we propose a novel spatial-temporal graph model (STGM-MHA) based on multihead attention for the purpose of pronunciation feature prediction of Chinese poetry. The STGM-MHA is designed using an encoder-decoder structure. The encoder compresses the data into a hidden space representation, while the decoder reconstructs the hidden space representation as output. In the model, a novel gated recurrent unit (GRU) module (AGRU) based on multihead attention is proposed to extract the spatial and temporal features of MFCC data effectively. The evaluation comparison of our proposed model versus state-of-the-art methods in six datasets reveals the clear advantage of the proposed model.

Background Breast cancer represents the second most deadly malignancy in women, and long noncoding RNAs (lncRNAs) have crucial functions in its development. Objective To investigate effects of the promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) on epithelial-mesenchymal transition (EMT) in breast cancer cells and their proliferation. Methods lncRNAs potentially regulating the transcriptional activity of the E-cadherin (E-cad, an epithelial cell marker) gene promoter were screened using a dual-luciferase reporter assay. PANDAR was overexpressed in Michigan cancer foundation 7 (MCF-7) breast cancer cells. E-cad and N-cadherin (N-cad, a mesenchymal cell marker) levels were detected by immunoblotting. Cell viability was assessed using a cell counting kit-8. Results PANDAR and TCONS00068220/LOC105375819 conservatively regulated the promoter activity of E-cad. PANDAR overexpression in MCF-7 inhibited E-cad expression, but upregulated N-cad. The enhanced expression of PANDAR promoted cell proliferation. Conclusion PANDAR is a key transcriptional repressor of E-cad and has regulatory effects on the promotion of cell proliferation. PANDAR is an oncogene in breast cancer, potentially facilitating the EMT process and promoting cell proliferation.

Bone fractures and defects pose serious health-related issues on patients. For clinical therapeutics, synthetic scaffolds have been actively explored to promote critical-sized bone regeneration, and electrical stimulations are recognized as an effective auxiliary to facilitate the process. Here, we develop a three-dimensional (3D) biomimetic scaffold integrated with thin-film silicon (Si)–based microstructures. This Si-based hybrid scaffold not only provides a 3D hierarchical structure for guiding cell growth but also regulates cell behaviors via photo-induced electrical signals. Remotely controlled by infrared illumination, these Si structures electrically modulate membrane potentials and intracellular calcium dynamics of stem cells and potentiate cell proliferation and differentiation. In a rodent model, the Si-integrated scaffold demonstrates improved osteogenesis under optical stimulations. Such a wirelessly powered optoelectronic scaffold eliminates tethered electrical implants and fully degrades in a biological environment. The Si-based 3D scaffold combines topographical and optoelectronic stimuli for effective biological modulations, offering broad potential for biomedicine.

Background The establishment of different cell types during organogenesis in mouse early embryos has been well studied. However, cell type differentiation and its molecular mechanisms in early embryo development in Mongolian sheep are not well understood. Results In this study, we present the first comprehensive single-cell transcriptomic characterization of Ujumqin sheep and Hulunbuir short-tailed sheep at E16. Thirteen major cell types were identified in Ujumqin sheep at E16, and 8 major cell types were identified in Hulunbuir short-tailed sheep at E16. Functional enrichment analysis showed that several pathways were significantly enriched in the notochord cluster, namely, the TGF-beta signaling pathway, Hippo signaling pathway, platelet activation pathway, riboflavin metabolism pathway, Wnt signaling pathway, regulation of actin cytoskeleton, and insulin signaling pathway. In contrast, glutathione metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle, thyroid hormone synthesis, pyruvate metabolism, cysteine and methionine metabolism, thermogenesis, and the VEGF signaling pathway were significantly enriched in the spinal cord cluster. Steroid biosynthesis, riboflavin metabolism, cell cycle, Hippo signaling, Hedgehog signaling, FOXO signaling, JAK-STAT signaling, and Wnt signaling were significantly enriched in the paraxial mesoderm cluster. The notochord cluster, spinal cord cluster and paraxial mesoderm cluster were all strongly related to tail development. Pseudotime analysis demonstrated that mesenchyme can contribute to the notochord in Ujumqin sheep. Further molecular assays showed that the Hippo signaling pathway was enriched in Ujumqin sheep. Conclusion This comprehensive single-cell map reveals the contributions of a previously unrecognized signaling pathway and contributes to our understanding of the mechanism of tail development in short-tailed sheep.

An artificial periosteum composed of hierarchically assembled Mg-doped MC microfibrils with a biomimetically rotated lamellar structure and osteogenic/angiogenic activities was successfully fabricated via a “multiscale cascade regulation” strategy.

At this stage, bone defects caused by trauma, infection, tumor, or congenital diseases are generally filled with autologous bone or allogeneic bone transplantation, but this treatment method has limited sources, potential disease transmission and other problems. Ideal bone-graft materials remain continuously explored, and bone defect reconstruction remains a significant challenge. Mineralized collagen prepared by bionic mineralization combining organic polymer collagen with inorganic mineral calcium phosphate can effectively imitate the composition and hierarchical structure of natural bone and has good application value in bone repair materials. Magnesium, strontium, zinc and other inorganic components not only can activate relevant signaling pathways to induce differentiation of osteogenic precursor cells but also stimulate other core biological processes of bone tissue growth and play an important role in natural bone growth, and bone repair and reconstruction. This study reviewed the advances in hydroxyapatite/collagen composite scaffolds and osseointegration with natural bone inorganic components, such as magnesium, strontium and zinc.

Bone tissue engineering (BTE) has been proven to be an effective method for the treatment of bone defects caused by different musculoskeletal disorders. Photocrosslinkable hydrogels (PCHs) with good biocompatibility and biodegradability can significantly promote the migration, proliferation and differentiation of cells and have been widely used in BTE. Moreover, photolithography 3D bioprinting technology can notably help PCHs-based scaffolds possess a biomimetic structure of natural bone, meeting the structural requirements of bone regeneration. Nanomaterials, cells, drugs and cytokines added into bioinks can enable different functionalization strategies for scaffolds to achieve the desired properties required for BTE. In this review, we demonstrate a brief introduction of the advantages of PCHs and photolithography-based 3D bioprinting technology and summarize their applications in BTE. Finally, the challenges and potential future approaches for bone defects are outlined.

In this work, an effective method is proposed to enable spatial modulation of the stiffness of elastic substrate through selectively controlling the formation of cross-linked interpenetrating network (IPN). The IPN structure is locally growing on the monomer-injected elastomer through selective ultraviolet light exposure, and the Young’s modulus of selected regions can be significantly enhanced by an order of magnitude. Further experiments and finite element analysis results demonstrate that the selective region exhibits 100% strain isolation characteristic. Finally, a metal oxide thin film transistor (MOTFT) array is integrated on the substrates exhibiting negligible performance variation under 100 % tensile strain and 500 tensile cycling. Our strategy opens up a promising way for fabrication of stretchable substrate.

Facial nerves are fragile and easily injured, for example, by traffic accidents or operations. Facial nerve injury drastically reduces the quality of life in affected patients, and its treatment presents clinical challenges. A promising therapeutic strategy includes nerve conduits with appropriate fillers capable of guiding nerve regeneration. In this study, a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) assembled via electrospinning and molecular self-assembly was first used to mimic the architecture of the native fibrin cable, which is similar to the nerve extracellular matrix (ECM). AFG as a substrate in chitosan tubes (CST) was used to bridge a 7 mm-long gap in a rabbit buccal branch facial nerve defect model. The results showed that AFG and CST showed good compatibility to support the adhesion, activity, and proliferation of Schwann cells (SCs). Further morphological, histological, and functional analyses demonstrated that the regenerative outcome of AFG-prefilled CST was close to that of autologous nerve grafts and superior to that of CST alone or CSTs prefilled with random fibrin nanofiber hydrogel (RFG), which indicated that AFG-prefilled CST markedly improved axonal regeneration with enhanced remyelination and functional recovery, thus showing great potential for clinical application for facial nerve regeneration treatments.

The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration. Recently, using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention. Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials. In this study, we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ (RGI) and KLTWQELYQLKYKGI (KLT) to construct an artificial neurovascular microenvironment. The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma (PC12) cells and tube-like structures formation of human umbilical vein endothelial cells (HUVECs) in vitro, and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model. Using indirect co-culture models, we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs. When the two cells types were directly co-cultured on the dual-functionalized peptide hydrogel, the efficiency of cell-cell communication was enhanced, which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology, and HUVECs tube-like structure formation. In summary, the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Organic smart fluorophores (OSFs) are highly desirable over the past decades because of their potential applications in advanced photonic devices. However, it is still difficult and challenging to obtain such materials with tunable photophysical properties and high emission efficiency based on robust construction strategies. Therefore, we proposed a simple and efficient strategy for constructing OSFs by balancing the competition between intermolecular interactions and external stimuli via molecular structure design. In this work, four pyrene derivatives (T1-Py, T4-Py, T12-Py, and S12-Py) with tunable stimuli-responsive properties were designed and synthesized. The tunable intermolecular interactions in solution states were successfully demonstrated by the molecular structure and solution concentration-dependent luminescence properties. The effect of alkyl chain length on molecular packing in solid states was investigated by polarized optical microscopy and powder and single-crystal X-ray diffraction; the results show that with the increase in molecular chain length, the molecular packing of the compounds gradually changed from π-π stacked compact mode to X-crossing stacked loose mode, which leads to different stimuli-responsive phenomena of these compounds. The strategy provided herein facilitates the construction of multistimuli-responsive (thermochromism, mechanochromism, and vapochromism) OSFs with adjustable emission color. Harnessing the heat-responsive luminescence properties and great solubility of T12-Py, the optical information anticounterfeiting based on temperature was demonstrated by printing different concentrations of T12-Py solution on filter papers. Much more, this research may provide broad implications for the design of organic smart materials based on intermolecular interactions.

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV‐mediated TGF‐β1 intercellular transfer is involved in the drug‐resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis‐associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF‐β1 is enriched in sEVs from the resistant cells. The sEV‐mediated TGF‐β1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV‐mediated drug‐resistant transmission by delivering TGF‐β1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV‐mediated TGF‐β1 intercellular transfer contributes to adriamycin resistance in BCa., Here, we show that small extracellular vesicles (sEVs) from adriamycin‐resistant breast cancer cells could confer resistance to adriamycin‐sensitive breast cancer cells. sEVs increased cell proliferation by inhibiting apoptosis and promoted cell mobility by enhancing EMT. sEV‐derived TGF‐β1 activated the TGF‐β1/Smad2 signaling pathway in recipient cells.

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Myelin sheath reconstruction plays an important role in peripheral nerve regeneration. But the hindered reconstruction of myelin sheath, due to the inadequate repair phenotypes of macrophages and Schwann cells after peripheral nerve injury, often causes poor functional nerve recovery. Here, biomechanically-adapted immunohydrogels are prepared as the FK506-loaded platforms and nerve tissue engineering scaffolds to reconstruct myelin sheath for peripheral nerve regeneration. By immunofluorescent staining, an increase in the proportion of F4/80

Atherosclerosis (AS) is a common systemic disease with increasing morbidity and mortality worldwide. Traditional Chinese medicine (TCM) with characteristics of multiple pathways and targets, presents advantages in the diagnosis and treatment of atherosclerosis.With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for AS treatment have been gradually revealed. Therefore, it is necessary to examine the existing studies on TCM therapies aimed at regulating AS over the past two decades.Using "atherosclerosis" and "Traditional Chinese medicine" as keywords, all relevant TCM literature published in the last 10 years was collected from electronic databases (such as Elsevier, Springer, PubMed, CNKI, and Web of Science), books and papers until March 2022, and the critical information was statistically analyzed.In this review, we highlighted extracts of 8 single herbs, a total of 41 single active ingredients, 20 TCM formulae, and 25 patented drugs, which were described with chemical structure, source, model, efficacy and potential mechanism.We summarized the cytopathological basis for the development of atherosclerosis involving vascular endothelial cells, macrophages and vascular smooth muscle cells, and categorically elaborated the medicinal TCM used for AS, all of which provide the current evidence on the better management of atherosclerosis by TCM.