Search

The lack of training data in new domain is a typical problem for named entity recognition (NER). Currently, researchers have introduced “entity trigger” to improve the cost-effectiveness of the model. However, it still required the annotator to attach additional trigger label, which increases the workload of the annotator. Moreover, this trigger applies only to English text and lacks research into other languages. Based on this problem, we have proposed a more cost-effective trigger tagging method and matching network. The approach not only automatic tagging entity triggers based on the characteristics of Chinese text, but also adds mogrifier LSTM to the matching network to reduce context-free representation of input tokens. Experiments on two public datasets show that our automatic trigger is effective. And it achieves better performances with automatic trigger than other state-of-the-art methods (The F1-scores increased by 1∼4).

In this paper, a neural network algorithm is used to conduct in-depth research and analysis on the sales dynamics prediction of virtual community knowledge sharing in cross-border e-commerce. Both the expected returns and the social network structure are analyzed, and both have positive effects on knowledge sharing in the actual development process, but the degree of them also possesses certain variability. A model of the factors influencing the quality of knowledge shared by users is constructed to explore the relationship between the dimensions in social capital and how they affect the community users’ perceptions of knowledge quality. Exploring the strong influencing factors of product repurchase rate has key implications for promoting product sales and sales forecasting. The scale of this paper has undergone several minor revisions, and the content validity is very good. Criterion validity is generally reflected by Person correlation coefficient, and construct validity includes exploratory factor analysis and confirmatory factor analysis. First, the values were clustered, and the optimal variables were selected using stepwise regression and fitted with Poisson regression models to explore the relationship between the repurchase rate of different products and the factors that strongly influence the repurchase rate in the case. To predict the sales of goods, the advantages of the BP neural network, LSTM neural network, and Verhulst gray model are combined: BP neural network can predict sales by combining the current data corresponding to independent variables, LSTM neural network can explore the influence of historical data on sales, and Verhulst model can predict sales based on the growth trend of variables. A BP-LSTM-Verhulst nested neural network based on the AP algorithm is constructed to predict sales volume, and the accuracy of this method is proved by example. Finally, it is found that the proposed sales prediction method has higher accuracy than exponential regression and shallow neural networks. The deep learning prediction method combining unstructured data such as images proposed in the paper not only provides a more accurate sales prediction method for short life cycle products in e-commerce but also provides an effective deep learning method for management practices. The KMO value obtained after the test is less than 0.5, which is not suitable for factor analysis. Using SPSS22.0 to expand the KMO value and Bartlett’s sphericity test, the KMO value is significantly greater than the minimum requirement of 0.5, the KMO value of self-efficacy is 0.826, and the KMO value of expected return is 0.870.

Facial expression recognition is a current research hotspot and can be applied to computer vision fields such as human-computer interaction and affective computing. The lack of diversity and category recognition information in the neural network input may affect the performance of the network, resulting in insufficient extraction of facial expression features. In order to address the above problems, a lightweight deep convolution neural network with convolution block attention module is proposed in this paper. The implementation of the lightweight DNN relies on the use of deep separable convolution and residual blocks. The combination of the convolution block attention module and the improved classification function can optimize the lightweight model. We use accuracy and confusion matrix to evaluate different models, ultimately achieving 71.5% and 99.5% accuracy on the Fer2013 and CK+ datasets respectively. The experimental results show that our model has good feature representation capabilities.

Background: Posterior internal fixation is the main method used for the treatment of thoracolumbar fractures. Fractures often occur in the upper 1/3 of the vertebral body. However, they can also occur in the middle or lower 1/3 of the vertebral body. At present, there is no report discussing the potential effects of sagittal location on instrument biomechanics or surgical strategy. The objects of this study was to investigate the effect of the sagittal location of the fracture region of the vertebral body on the biomechanics of the internal fixation system and surgical strategy. Methods: A finite element model of the T11-L3 thoracolumbar segment was established based on a healthy person’s CT scan. Different sagittal fracture location finite element models were created by resection of the upper 1/3, middle 1/3, and lower 1/3 of the L1 vertebral body. Three surgical strategies were utilized in this study, namely proximal 1 level and distal 1 level (P1-D1), proximal 2 level and distal 1 level(P2-D1), and proximal 1 level and distal 2 levels (P1-D2). Nine fixation finite element models were created by combining fracture location and fixation strategies. Range of motion, von Mises stress, and stress distribution were analyzed to evaluate the effects on the instrument biomechanics and the selection of surgical strategy. Results: In all three different fixation strategies, the maximum von Mises stress location on the screw did not change with the sagittal location of the fracture site; nevertheless, the maximum von Mises stress differed. The maximum rod stress was located at the fracture site, with its value and location changed slightly. In the same fixation strategy, a limited effect of sagittal location on the range of motion was observed. P2D1 resulted in a shorter range of motion and lower nail stress for all sagittal locations of the fracture compared with the other strategies; however, rod stress was similar between strategies. Conclusions: The sagittal location of a fracture may affect the stress and distribution, but does not influence the selection of surgical strategy.

Background: PD-1 blockade has shown impressive clinical outcomes in colorectal cancers patients with high microsatellite instability (MSI-H). However, the majority of patients with colorectal cancer who present low microsatellite instability (MSI-L) or stable microsatellites (MSS) show little response to PD-1 blockade therapy. Here, we have demonstrated that Shikonin (SK) could induce cell death of CT26 cells via classically programmed and immunogenic pathways. Methods and Results: SK promoted the membrane exposure of calreticulin and upregulated the expression of heat shock protein 70 (Hsp70). The upregulation of Hsp70 was dependent on ROS induced by SK and silencing of PKM2 in CT26 cells reverts ROS upregulation. Besides, SK synergizes with PD-1 blockade in CT26 xenograft mice model, with the increase of intramural DC cells and CD8+T cells. The expression of Hsp70 in tumor tissue was also increased in combinational SK plus αPD-1 therapy group. Conclusions: Our study elucidated the potential role of ‘Shikonin-PKM2-ROS-Hsp70-ICD’ axis in the promotion of efficacy of PD-1 blockade in CRC treatments, providing a potential strategy and targets for improving the efficacy of PD-1 blockade in colorectal cancer.

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

This study analyzed the impact of factors affecting overall survival in patients with pT2N0M0 esophageal squamous carcinoma (ESCC) and developed a nomogram to predict overall survival (OS). We reviewed the clinical data of 413 patients with pathological T2N0M0 ESCC after radical esophagectomy in two hospitals. Data from one institution was used as the training cohort. A nomogram was established using Cox proportional hazard regression for identifying the prognostic factors affecting for OS in ESCC patients. The area under the curve (AUC), calibration curves and decision curve analysis (DCA) were used to evaluate prognostic efficacy, which was validated in an independent validation cohort. In the training cohort (N = 304), the median OS was 69.33 months, and the 3-, 5- and 10-year OS rates were 76.80%, 67.00% and 56.90%, respectively. The median OS of the validation cohort (N = 109) was 73.50 months, and the 3-, 5- and 10-year OS rates were 77.00%, 67.80% and 55.60%, respectively. According to Cox univariate and multivariate analyses, sex, age, tumor length and the number of resected lymph nodes were identified as predictors of OS. We developed nomograms and performed internal and external validation. The time-dependent receiver operating characteristic (ROC) curve and area under the curve (AUC) value, calibration curve and decision curve analysis (DCA) showed good prediction ability of the nomogram. The developed nomogram can effectively predict OS after esophagectomy in patients with pT2N0M0 ESCC.

The inhospitable niche at the injury site after spinal cord injury (SCI) brings several challenges to neural stem cell (NSC) therapy, such as limited NSC retention and neuronal differentiation. Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells. Herein, an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc (AFGN) was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair. The AFGN hydrogel provides multimodal cues, including oriented nanofibrous topography, soft stiffness, and specific cell binding ligand, for directing NSC functions and nerve regeneration. The conjugated N-Cadherin-Fc recapitulated the homophilic cell–cell interaction for NSCs’ adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation. In addition, the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention, immunomodulation, neuronal differentiation, and in vivo integration with inherent neurons, thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery. Altogether, this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche. Graphical abstract

New legislation adopting a tough criminal stance on the crimes of corruption and bribery responds to the need for strengthening Chinese anti-corruption work. The ninth amendment to the Chinese Criminal Law Code, which adds life imprisonment without parole or commutation, has received broad support from all sectors of society. The aim of the amendment, as stated by the legislature, is to safeguard judicial fairness and prevent criminals convicted of the most serious corruption offences from having their prison sentences shortened through commutation. This stated legislative aim is not acceptable. Whether from the perspective of deterrence or alternative measures to the death penalty, the approach of adding life imprisonment without parole or commutation in order to punish the corrupt is not ideal. This article argues that, given the particular nature of crimes of corruption and given the disadvantages of life imprisonment without parole or commutation, restraint in the use of the death penalty does not mean that life imprisonment has to be used as an alternative measure. Moreover, the death penalty with a two-year reprieve is sufficient for realising retribution and prevention as aims of punishment.

Ginseng is a perennial herb with a long growth cycle and is known to easily accumulate pesticides during its growth process, seriously threatening people's health. Therefore, to ensure safe consumption, it is necessary to detect and monitor pesticide residues in ginseng. In this study, a novel analysis method was established for simultaneous determination of 31 pesticides in ginseng by high-performance liquid chromatography-mass spectrometry. Ginseng samples were extracted using acetonitrile, cleaned up by primary secondary amine (PSA) solid-phase extraction column eluted with acetonitrile-toluene, and then detected in multiple reaction mode (MRM). The calibration curves of target compounds were linear in the range of 0.005–1.0 mg/L, with correlation coefficients greater than 0.9921. The limits of detection of all the pesticides in ginseng were between 4.4×10−5 and 1.6 × 10−2 mg/kg. For fresh ginseng, the average recoveries ranged from 72.1 to 111.6%, and the relative standard deviations were 1.3–12.2%. For dry ginseng, the average recoveries were 74.3–108.3%, and the relative standard deviations were 0.9–14.9%. The residual concentrations of some pesticides in real samples were greater than the maximum residue limit (MRL) for European Union (EU). The method established here is rapid and simple with high sensitivity and good reproducibility, which is sensitive in the residue analysis of many pesticides in ginseng.

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.

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.

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.

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.

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.

A new nerve guidance conduits (NGCs) named MC@Col containing Type I collagen (Col) and mineralized collagen (MC) was developed, enhancing mechanical and degradation behavior. The physicochemical properties, the mechanical properties and in vitro degradation behavior were all evaluated. The adhesion and proliferation of Schwann cells (SCs) were observed. In the in vivo experiment, MC@Col NGC and other conduits including Col, chitosan (CST) and polycaprolactone (PCL) conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect. Histological analyses, morphological analyses, electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks. The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC. In vitro cytocompatibility evaluation revealed that the SCs had good viability, attachment and proliferation in the MC@Col. In in vivo results, the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects, but superior to those by Col, CST and PCL conduits. The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration, thus showing great promising potential as a new type of conduit in clinical applications.

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.

The hydration of C

We demonstrate the construction of the optical system in the atomic clock-beyond atomic fountain based on 87Rb atom. The optical system includes a high-stability laser system and an optical lattice. The high-stability laser system with the new scheme of frequency locking and shift is introduced in detail, which is an important laser source for laser cooling. The optimized frequency and intensity stability are achieved to 4 × 10–14τ−1/2 (τ is the averaging time) and 4 × 10–5τ−1/2, respectively, which are highly stable. On the basis of the conventional atomic fountain clock, the optical lattice is specially investigated along the direction of gravity and its characteristics are studied systematically. For the optimized and novel exploration, we predict the achievable stability of 3.6×10−14τ−1/2 and it has the potential to be improved to 3.6×10−15τ−1/2. The realizability of the construction due to the stabilized laser and optical lattice makes the beyond fountain promising candidate for the next-generation high performance microwave atomic clock.

Devices with sensing-memory-computing capability for the detection, recognition and memorization of real time sensory information could simplify data conversion, transmission, storage, and operations between different blocks in conventional chips, which are invaluable and sought-after to offer critical benefits of accomplishing diverse functions, simple design, and efficient computing simultaneously in the internet of things (IOT) era. Here, we develop a self-powered vertical tribo-transistor (VTT) based on MXenes for multi-sensing-memory-computing function and multi-task emotion recognition, which integrates triboelectric nanogenerator (TENG) and transistor in a single device with the simple configuration of vertical organic field effect transistor (VOFET). The tribo-potential is found to be able to tune ionic migration in insulating layer and Schottky barrier height at the MXene/semiconductor interface, and thus modulate the conductive channel between MXene and drain electrode. Meanwhile, the sensing sensitivity can be significantly improved by 711 times over the single TENG device, and the VTT exhibits excellent multi-sensing-memory-computing function. Importantly, based on this function, the multi-sensing integration and multi-model emotion recognition are constructed, which improves the emotion recognition accuracy up to 94.05% with reliability. This simple structure and self-powered VTT device exhibits high sensitivity, high efficiency and high accuracy, which provides application prospects in future human-mechanical interaction, IOT and high-level intelligence.

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.

Background: Periodontitis is associated with periodontal tissue damage and teeth loss. Nonalcoholic fatty liver disease (NAFLD) has an intimate relationship with periodontitis. Nevertheless, interacted mechanisms between them have not been clear. This study was intended for the exploration of shared gene signatures and latent therapeutic targets in periodontitis and NAFLD.Methods: Microarray datasets of periodontitis and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was utilized for the acquisition of modules bound up with NAFLD and periodontitis. We used ClueGO to carry out biological analysis on shared genes to search their latent effects in NAFLD and periodontitis. Another cohort composed of differential gene analysis verified the results. The common microRNAs (miRNAs) in NAFLD and periodontitis were acquired in the light of the Human microRNA Disease Database (HMDD). According to miRTarbase, miRDB, and Targetscan databases, latent target genes of miRNAs were forecasted. Finally, the miRNAs–mRNAs network was designed.Results: Significant modules with periodontitis and NAFLD were obtained via WGCNA. GO enrichment analysis with GlueGo indicated that damaged migration of dendritic cells (DCs) might be a common pathophysiologic feature of NAFLD and periodontitis. In addition, we revealed common genes in NAFLD and periodontitis, including IGK, IGLJ3, IGHM, MME, SELL, ENPP2, VCAN, LCP1, IGHD, FCGR2C, ALOX5AP, IGJ, MMP9, FABP4, IL32, HBB, FMO1, ALPK2, PLA2G7, MNDA, HLA-DRA, and SLC16A7. The results of differential analysis in another cohort were highly accordant with the findings of WGCNA. We established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis. Finally, the analysis of miRNA pointed out that hsa-mir-125b-5p, hsa-mir-17-5p, and hsa-mir-21-5p might provide potential therapeutic targets.Conclusion: Our study initially established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis, found that damaged migration of DCs might be a common pathophysiological feature of NAFLD and periodontitis, and provided potential therapeutic targets.

JMJD6 is a member of the JmjC domain-containing family and has been identified as a promising therapeutic target for treating estrogen-induced and triple-negative breast cancer. To develop novel anti-breast cancer agents, we synthesized a class of N-(1-(6-(substituted phenyl)-pyridazine-3-yl)-piperidine-3-yl)-amine derivatives as potential JMJD6 inhibitors. Among them, the anti-cancer compound A29 was an excellent JMJD6 binder (KsubD/sub = 0.75 ± 0.08 μM). It could upregulate the mRNA and protein levels of p53 and its downstream effectors p21 and PUMA by inhibiting JMJD6. Besides, A29 displayed potent anti-proliferative activities against tested breast cancer cells by the induction of cell apoptosis and cell cycle arrest. Significantly, A29 also promoted a remarkable reduction in tumor growth, with a TGI value of 66.6% (50 mg/kg, i.p.). Taken together, our findings suggest that A29 is a potent JMJD6 inhibitor bearing a new scaffold acting as a promising drug candidate for the treatment of breast cancer.