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Current knowledge graph-based recommendation methods heavily rely on high-quality knowledge graphs, often falling short in effectively addressing issues such as the cold start problem and heterogeneous noise in user interactions. This leads to biases in user interest and popularity. To overcome these challenges, this paper introduces a novel recommendation approach termed Knowledge-enhanced Perceptive Graph Attention with Graph Contrastive Learning (KPA-GCL), which leverages relational graph convolutional neural networks. The proposed method optimizes the triplet embedding representation of entity-item interactions based on relationships between adjacent entities in a heterogeneous graph. Subsequently, a graph convolutional neural network is employed for enhanced aggregation. Similarity scores from a contrastive view serve as the selection criterion for high-quality embedded representations, facilitating the extraction of refined knowledge subgraphs. Multiple adaptive contrast-loss optimization functions are introduced by combining Bayesian Personalized Ranking (BPR) and hard negative sampling techniques. Comparative experiments are conducted with ten popular existing methods using real public datasets. Results indicate that the KPA-GCL method outperforms compared methods in all datasets based on Recall, NDCG, Precision, and Hit-ratio measures. Furthermore, in terms of mitigating cold start and noise, the KPA-GCL method surpasses other ten methods. This validates the reasonability and effectiveness of KPA-GCL in real-world datasets.

Perforation of the tympanic membrane (TM) is a common condition that often requires a scaffold as a support for surgery. However, because of the external environment of the auditory canal, the scaffold could become bacterially infected and prevent the TM from healing. As a result, the perfect scaffold should have both antibacterial and biomimetic qualities. In this study, the biodegradable biomaterial poly(1,4-butylene carbonate) (PBC) films containing levofloxacin (LEV) was successfully prepared for the first time. The results showed that the hydrophilicity of the LEV/PBC film was improved after the addition of LEV, and the tensile strength was also complied with the requirements of the standard. The created antibacterial film demonstrated excellent antibacterial properties. In vitro hemolysis experiments revealed no risk of hemolysis for the new material, and the cytotoxicity study further confirmed its non-cytotoxic nature. Overall, LEV was a good component of PBC/LEV film, which is expected to be used for TM repair in the future.

In recent years, significant advancements in nanotechnology have yielded remarkable improvements in biomedical applications. Nanocarriers, harnessed from the principles of nanotechnology, have garnered widespread utilization in medicine delivery and diagnostics. However, the progression of nanocarriers has been hindered by two key challenges: low drug loading capacity and the potential for carrier-induced toxicity. To surmount these obstacles, the rapid development and expansion of carrier-free drug delivery systems (CFDDSs) composed of pure drugs and prodrugs have emerged as a promising solution. Extensive endeavors have been undertaken to explore novel excipients, therapeutic agents, self-assembly processes, and therapeutic mechanisms, aimed at expanding the horizons of CFDDSs and enhancing their therapeutic efficacy. This comprehensive review provides an overview of CFDDSs, elucidating their self-assembly mechanisms. Additionally, we examine their diverse biomedical applications while shedding light on the challenges ahead for the future development and clinical implementation of CFDDSs. This review serves to enhance our understanding of the intricate mechanisms governing drug nanoassembly formation and fosters the advancement of CFDDSs in the expansive realm of biomedical research.

Community detection in complex networks often suffers from insufficient data and limited utilization of prior knowledge. In this paper we propose “Semi-supervised Generative Adversarial Network” (GANSE), a novel algorithm that integrates Generative Adversarial Networks (GANs) and semi-supervised learning to address these challenges. This method addresses the issues above through a multi-step process. Initially, the network is rewired using vertex similarity metrics, thereby enhancing its structural integrity. Subsequently, a novel generative adversarial network model is designed, and our model facilitates the reconstruction of the network, thereby yielding partitions. Which form the basis for identifying core communities. Additionally, the local clustering coefficient is incorporated as a reward signal and injected into the node selection process. Moreover, isolated nodes are reallocated, ultimately culminating in the derivation of the final community structure. Experimental results on four large real-life datasets demonstrate the clear superiority of the proposed algorithm in terms of F1 and Jaccard metrics when compared to existing algorithms. Notably, our GANSE method outperforms the traditional algorithms in networks with “missing data”. Thus showing its robustness and effectiveness in real-world incomplete datasets. Our findings highlight the potential of GANs and semi-supervised learning for enhancing community detection accuracy in complex networks.

Salt and drought stress has been an important factor limiting agricultural production, and SA is an important phenolic involved in stress response, but the function of SA in response to dual salt and drought stress in rice is not clear. In this study, the effects and mechanisms of exogenous SA-triggered in rice adaptation to dual salt and drought stress were investigated by detecting physiological and biochemical indexes and the expression of salt and drought tolerance genes. The results showed that the application of SA could significantly increase the antioxidant enzyme activities of rice seedlings under salt and drought stress, thereby reducing the contents of rice H2O2 and MDA and maintaining the growth of rice seedlings. Moreover, the expression of genes involved in the response of abiotic stress, such as OsDREB2A, OsSAPK8, OsSAPK10 and OsMYB2, were up-regulated under salt and drought treatment, and SA application could further enhance the expression of those genes like OsDREB2A and OsSAPK8, suggesting that SA might regulate antioxidant enzyme activity via inducing the expression of salt and drought tolerance genes and enhancing the salt and drought tolerance of rice. The results will enrich the knowledge of the function of SA and provide a reference for studying the mechanism of SA in the salt and drought resistance of rice, and breeding new rice germplasm with improved salt and drought resistance.

Summary: Hyperactivity of pyramidal neurons (PNs) in CA1 is an early event in Alzheimer’s disease. However, factors accounting for the hyperactivity of CA1 PNs remain to be completely investigated. In the present study, we report that the serotonergic signaling is abnormal in the hippocampus of hAPP-J20 mice. Interestingly, chemogenetic activation of serotonin (5-hydroxytryptamine; 5-HT) neurons in the median raphe nucleus (MRN) attenuates the activity of CA1 PNs in hAPP-J20 mice by regulating the intrinsic properties or inhibitory synaptic transmission of CA1 PNs through 5-HT3aR and/or 5-HT1aR. Furthermore, activating MRN 5-HT neurons improves memory in hAPP-J20 mice, and this effect is mediated by 5-HT3aR and 5-HT1aR. Direct activation of 5-HT3aR and 5-HT1aR with their selective agonists also improves the memory of hAPP-J20 mice. Together, we identify the impaired 5-HT/5-HT3aR and/or 5-HT/5-HT1aR signaling as pathways contributing to the hyperexcitability of CA1 PNs and the impaired cognition in hAPP-J20 mice.

NLRP3 inflammasome is a key mediator in ischemic stroke-induced neuroinflammation and subsequent brain injury. Our previous study demonstrated the potent activity of Pien-Tze-Huang (PTH), a well-known Chinese patent formula, in reducing mitochondria-mediated neuronal apoptosis in cerebral ischemia/reperfusion impaired rats. This study aims to elucidate the mechanistic action of PTH related to neuroinflammation in LPS-induced BV2 microglial cells and cerebral ischemia/reperfusion impaired rats. BV2 cells were stimulated with LPS for 12 h and treated with PTH with various concentrations. Modulation by PTH of relevant genes (IL-6, IL-1β, IL-18, TNF-α, COX-2 and iNOS mRNA) and proteins (NLRP3 inflammasome, autophagy and AMPK/mTOR/ULK signaling) was analyzed by real-time PCR and western blot, respectively. Similar analyses were conducted in middle cerebral artery occlusion rat model including neurological deficit, infarct volume, microglial activation, and key genes and proteins in modulating autophagy and NLRP3. Our results showed that PTH significantly inhibited the production of key proinflammatory mediators and protein expressions of NLRP3 and caspase-1 p20 in LPS induced BV2 cells. It also enhanced the autophagy response by modulating the key autophagy proteins via AMPK/mTOR/ULK related pathway. The reduced inflammatory responses and NLRP3 expressions by PTH were partially blocked by the autophagy inhibitor (3-MA) and AMPK blocker (compound C). In rats, PTH significantly reduced infarct size, suppressed microglial activation, and improved neuron deficit. It also promoted autophagy and reduced NLRP3 activity. Our study demonstrated that PTH inhibited NLRP3 inflammasome-mediated neuroinflammation, which was associated with enhanced autophagy via AMPK/mTOR/ULK1 pathway in vitro and in vivo.

Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels.

Bismaleimide (BMI), as a high-performance thermosetting resin, has been widely used to many cutting-edge fields, but the ability of difficult to dissolve and complicated post-treatment process has hindered the applications of BMI in Additive manufacturing technology. In this study, additive manufacturing of BMI is realized via UV-assisted direct ink writing (UV-DIW) of BMI resin inks followed by heat treatment. The inks are composed of prepolymer 4,4′-bismaleimidodiphenyl methane and 2,2′-diallylbisphenol A, diluent N-vinyl-2-pyrrolidone, and photo initiator Irgacure 819, which exhibit desirable UV curing performance and rheological properties for additively manufacturing various complex three-dimensional (3D) structures via UV-DIW at room temperature. The followed heat treatment results in BMI architectures with excellent mechanical properties, dimensional stability and thermoresistant properties with ~91 MPa tensile strength and at the same time realize the shrinkage of 2–3%, ~4 GPa Young's modulus, exceeding 370 °C decomposition temperature, and ~210 °C glass transition temperature, which are comparable to that of traditionally molding BMI. The 3D architectures with outstanding performances are promising in fields ranged from microelectronics to aerospace and automotive industries. Keywords: 3D printing, Bismaleimide, Direct ink writing, Additive manufacturing

Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP). However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ) or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG) of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

Glycyrrhiza uralensis is considered to be one of the most important herbs in traditional Chinese medicine due to its numerous pharmacological effects particularly its ability to relieve cough and act as a mucolytic. Based on previous research, these effects are mediated by a number of active ingredients, especially glycyrrhizic acid (GA). In the present study, a gene encoding β-amyrin synthase (β-AS) involved in GA biosynthesis in G. uralensis has been cloned and expressed in Saccharomyces cerevisiae. The cloned enzyme showed similar activity to native enzymes isolated from other Glycyrrhiza species to catalyze the conversion of 2,3-oxidosqualene into β-amyrin. In fact the β-AS gene is particularly important in the GA biosynthetic pathway in G. uralensis. The complete sequence of the enzyme was determined and a phylogenetic tree based on the β-AS gene of G. uralensis and 20 other species was created. This showed that Glycyrrhiza glabra had the closest kinship with G. uralensis. The results of this work will be useful in determining how to improve the efficacy of G. uralensis by improving its GA content and in exploring the biosynthesis of GA in vitro.

Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies.