Motor imagery electroencephalography (EEG) decoding is an essential part of brain-computer interfaces (BCIs) which help motor-disabled patients to communicate with the outside world by external ...devices. Recently, deep learning algorithms using decomposed spectrums of EEG as inputs may omit important spatial dependencies and different temporal scale information, thus generated the poor decoding performance. In this paper, we propose an end-to-end EEG decoding framework, which employs raw multi-channel EEG as inputs, to boost decoding accuracy by the channel-projection mixed-scale convolutional neural network (CP-MixedNet) aided by amplitude-perturbation data augmentation. Specifically, the first block in CP-MixedNet is designed to learn primary spatial and temporal representations from EEG signals. The mixed-scale convolutional block is then used to capture mixed-scale temporal information, which effectively reduces the number of training parameters when expanding reception fields of the network. Finally, based on the features extracted in previous blocks, the classification block is constructed to classify EEG tasks. The experiments are implemented on two public EEG datasets (BCI competition IV 2a and High gamma dataset) to validate the effectiveness of the proposed approach compared to the state-of-the-art methods. The competitive results demonstrate that our proposed method is a promising solution to improve the decoding performance of motor imagery BCIs.
In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great ...challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.
Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal ...nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.
Acquired resistance remains a limitation of the clinical use of 5-fluorouracil (5-FU). Because exosomes, are important vesicles participating in intercellular communication, their contribution to the ...development of acquired 5-FU resistance needs to be elucidated. In this study, we aimed to examine the underlying mechanisms of exosomes from 5-FU resistant cells (RKO/R) in sustaining acquired 5-FU resistance in sensitive cells (RKO/P).
Exosomes from a 5-FU-resistant cell line (RKO/R) and its parental cell line RKO/P were isolated and co-cultured with 5-FU-sensitive cells. Real-time cellular analysis (RTCA) and FACS analysis were used to examine cell viability and apoptosis. Exosomal protein profiling was performed using shotgun proteomics. Inhibitors and siRNAs were applied to study the involvement of selected proteins in 5-FU resistance. The effect of exosomal p-STAT3 (Tyr705) on the caspase cascade was examined by western blotting (WB) and high content analysis. Xenograft models were established to determine whether exosomal p-STAT3 can induce 5-FU resistance in vivo.
Our results indicated that exosomes from RKO/R cells significantly promoted cell survival during 5-FU treatment. Proteomics and WB analysis results indicated that GSTP1 and p-STAT3 (Tyr705) were enriched in exosomes from RKO/R cells. Inhibition of p-STAT3 re-sensitized RKO/P cells to 5-FU via caspase cascade. Furthermore, p-STAT3 packaged by exosomes from RKO/R cells increased resistance of tumor cells to 5-FU in vivo.
Our results reveal a novel mechanism by which p-STAT3-containing exosomes contribute to acquired 5-FU resistance in CRC. This study suggests a new option for potentiating the 5-FU response and finding biomarkers for chemotherapy resistance.
•Two pharmaceutical salt hydrates of vortioxetine with maleic acid and fumaric acid were synthesized.•The two salt hydrates have been characterized by single crystal X-ray diffraction.•The ...solubilities and intrinsic dissolution rates of the two salt hydrates were evaluated in water and pH 6.86 phosphate buffer medium.
Vortioxetine (VOT) is a serotonin (5-HT) receptor antagonist used for the treatment of major depressive disorder, but its poor solubility limits its absorption in vivo. This study aimed to improve the solubility properties of VOT and modify its physicochemical properties by combining it with pharmaceutically acceptable coformer molecules. In this work, two pharmaceutical salt hydrates of VOT with maleic acid (MA) and fumaric acid (FA) were successfully prepared by solvent evaporation and the liquid-assisted grinding method. The obtained salt hydrates were systematically investigated by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis techniques. The solubility of the salt hydrates was evaluated in water and pH 6.86 phosphate buffer medium. The results suggested that the two VOT salt hydrates exhibited increased solubility compared to VOT. The intrinsic dissolution rates (IDRs) of each salt hydrates was also determined, indicting that MA and FA were dissolution accelerators in water.
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The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the ...design of bone microenvironment–specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.
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•MXene nanosheets could direct the selective growth of silk nanofibrils.•Prepared MXene/RSF hydrogel exhibited good conductivity and sensing ability.•The electroactive hydrogel could promote osteogenic differentiation of BMSCs by activating the Ca2+/CALM signaling pathway.•The conductive system created an osteoblast–macrophage–endotheliocyte virtuous circle for bone microenvironment.
Novel crystalline forms of febuxostat (HFEB) salts were synthesized by liquid-assisted cogrinding with 2-methylimidazole (2MI) and di-2-pyridylamine (DPA) and characterized by Hirshfeld surface ...analysis, IR, 1H NMR, single crystal and powder X-ray diffractions, TGA and DSC. Two new HFEB salts featured different stoichiometries: 2:1 molecular ratio in HFEB-2MI and 1:1 molecular ratio in HFEB-DPA. For HFEB-2MI salt, two HFEB molecules lost one proton forming a singly charged hydrogen carboxylate anion H(FEB)2−, which interacted with the disordered 2MI cation via the N3H3A⋯O1i (i: −x, −y, −z+1) and N4H4B⋯O1ii (ii: x, y+1, z−1) hydrogen bonds to form one-dimensional structure. For HFEB-DPA salt, one proton transferred from one HFEB to DPA, which were further connected by N4H1⋯O1 and N3H2⋯O2 hydrogen bonds to form an R22(8) ring motif. HFEB-2MI and HFEB-DPA salts exhibited increased equilibrium solubilities and intrinsic dissolution rates compared to those of HFEB in aqueous medium.
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•Two new febuxostat salts with 2-methylimidazole (2:1) and di-2-pyridylamine (1:1) were synthesized.•Two febuxostat salts have been characterized by different physical methods.•Equilibrium solubility and dissolution rates for two salts were carried out and discussed.•The work suggests that the salt form is a good strategy to improve the febuxostat solubility.
Evidence from multiple studies suggests metabolic abnormalities play an important role in lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. The present study aimed to ...explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility.
Transcriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro.
Samples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer susceptibility in males and 15 in females. Most of the metabolic cancer-susceptibility genes had high prediction accuracy for lung cancer (AUC > 0.9). Furthermore, both bioinformatics analysis and experimental results showed that TAOK2 was down-regulated and ASAH1 was up-regulated in male tumor tissue and female tumor tissue in LUAD. Functional experiments showed that inhibiting ASAH1 suppressed the proliferation, migration, and invasion of lung cancer cells.
Metabolic cancer-susceptibility genes may be used alone or in combination as diagnostic markers for LUAD. Further studies are required to elucidate the functions of these genes in LUAD.
Pityriasis rubra pilaris (PRP) is a rare heterogeneous group of papulosquamous inflammatory disorders with unknown etiology. PRP is often resistant to many conventional therapies which has made more ...challenging on treatment. More recently, several studies have shown encouraging clinical results of secukinumab in the treatment of PRP in adult, but no studies have explored its effects in children. We herein report a 7‐year‐old boy with severe type V PRP responded rapidly to secukinumab monotherapy (150 mg once weekly) when conventional therapies have failed. The patient showed rapid and dramatic improvement of erythema, palmoplantar hyperkeratosis, scaling, and itching within only 5 weeks, with no adverse effects. Secukinumab could be considered as a treatment option for refractory PRP in children, as recently reported in adult.
•Aggression, fear, anxiety and shoaling behaviors are markedly sexually dimorphic.•Male shoals are beneficial in dramatically alleviating anxiety levels in zebrafish.•Metabolites in zebrafish brains ...vary significantly between the sexes.•Brain metabolite differences as a potential mechanism for behavioral dimorphism.
The zebrafish (Danio rerio) has historically been a useful model for research in genetics, ecology, biology, toxicology, and neurobehavior. Zebrafish have been demonstrated to have brain sexual dimorphism. However, the sexual dimorphism of zebrafish behavior demands our attention, particularly. To evaluate the behavior and brain sexual dimorphisms in zebrafish, this study assessed sex differences in adult D. rerio in four behavioral domains, including aggression, fear, anxiety, and shoaling, and further compared with metabolites in the brain tissue of females and males. Our findings showed that aggression, fear, anxiety and shoaling behaviors were significantly sexually dimorphic. Interestingly, we also show through a novel data analysis method, that the female zebrafish exhibited significantly increased shoaling behavior when shoaled with male zebrafish groups and, for the first time, we offer evidence that male shoals are beneficial in dramatically alleviating anxiety in zebrafish. In addition, there were significant changes in metabolites in zebrafish brain tissue between the sexes. Furthermore, zebrafish behavioral sexual dimorphism may be associated with brain sexual dimorphism, with significant differences in brain metabolites. Therefore, to prevent the influence or even bias of behavioral sex differences on results, it is suggested that behavioral studies or behavioral-based other relevant investigations consider sexual dimorphism of behavior and brain.
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