Search

• A novel method (IdeSelf-Deep) is used to predict anti-coronavirus peptides. • The AAC, DC, CTD, PseAAC, CT, and AD methods are fused to extract antimicrobial peptides sequence features information. • K-means SMOTE algorithm is used to process the category imbalance data for the first time. • We firstly build a new deep learning framework which combines the BiLSTM, self- attention and fully connected neural network to predict the anti-coronavirus peptides. • IdeSelf-Deep increases the prediction performance compared with other methods. The disease caused by infection with the SARS-CoV-2 virus is threatening people's health and lives. Antimicrobial peptides (AMPs) with anti-coronavirus (anti-CoV) functions may be potentially effective therapeutics for the treatment of infected coronaviruses. Due to the complexity of experimental methods, it is particularly important to identify anti-CoV peptides by computational techniques. In this paper, we propose a new predictive model, called AntiCVP-Deep. First, six feature extraction methods are used to obtain the original feature vector of antimicrobial peptides, and K-means SMOTE is used to handle imbalance data. Then, the processed balanced sample data is passed through the input gate, forget gate and output gate of a bidirectional long short-term memory network (BILSTM) to select optimal features. Next, the important antimicrobial peptides information is given a higher weight through the self-attention mechanism, which enhances the model's ability to learn features. Finally, the data from self-attention layer are input into fully connected neural network (FCN) to predict anti-CoV peptides. The AUC values of the four datasets all reach above 98%. The geometric mean (GMean) of antivirus, non-AVP, non-AMP and all-Neg recognition on the independent test sets reach 90.05%, 92.63%, 99.46% and 91.24%, respectively. This experimental result shows that the AntiCVP-Deep method is helpful for identifying anti-CoV peptides and has better predictive performance compared to other existing predictive models. [ABSTRACT FROM AUTHOR]

With the explosive increase of remote sensing data, how to search for remote sensing data quickly and accurately in a vast dataset is an incredibly critical matter for research subjects. The deep hashing method has become the dominant method for remote sensing image retrieval because of its low-cost storage and high-speed retrieval. However, for the reason of the limitation of fixed convolutional kernels, deep hashing frameworks based on Convolutional Neural Networks (CNNs) fail to obtain the global semantic information well, which leads to the generation of suboptimal solutions. Furthermore, existing hashing methods commonly employ the random sampling strategy or hardest sample mining to build training batches, resulting in bad local minima. To remedy these problems, a novel Deep Global Semantic Structure-preserving Hashing framework via corrective triplet loss (DGSSH) is proposed for remote sensing image retrieval to learn a discriminative and stable embedding space, achieving intra-class confusion and inter-class diversity. Specifically speaking, the feature extraction module based on Swim Transformer architecture is developed to capture global semantic information and multiscale features from remote sensing images. Based on a distribution matching constraint, the corrective triplet loss for deep hashing schemes is designed to reduce the distribution shift caused by the random selection or hardest sample mining. Meanwhile, to reduce the time overhead of the model, the asymmetric learning strategy is employed to perform effective compact representation learning. Numerous experiments have been carried out on three publicly available benchmarks, which indicates that the proposed DGSSH framework could achieve optimal performance for remote sensing image retrieval applications. The source code of our DGSSH framework is hosted at https://github.com/QinLab-WFU/DGSSH.git. • The Swim Transformer architecture is developed to capture global semantic features. • The corrective triplet loss is proposed to reduce the distribution shift. • An asymmetric learning strategy is employed to improve training efficiency. • The state-of-the-art results are reported on three benchmark datasets. [ABSTRACT FROM AUTHOR]

Although targeted therapy using tyrosine kinase inhibitors (TKIs) has made remarkable progress in treating chronic myeloid leukemia (CML), this disease remains largely incurable, warranting further investigation of new therapeutic strategies. BCR-ABL is a highly specific tumor antigen in CML and provides an attractive opportunity for vaccination therapy. Exogenous antigens must be presented on MHC class I molecules—via a process termed cross-presentation—to activate specific cytotoxic T lymphocyte response. The relative efficiency of cross-presentation is determined in part by the ability of dendritic cells (DCs) to internalize and present antigens. Here, we present a novel tool that uses cytoplasmic transduction peptide (CTP) to facilitate the internalization of antigens by DCs in an endocytosis-independent manner, which greatly enhances the efficiency of antigen presentation, thereby inducing stronger cytotoxic activity to ensure the elimination of CML cells. The data suggest that CTP-fused CML-specific peptides can be applied in vaccination therapies for CML patients. • Peptides derived from the junctional region of BCR-ABL are presented by MHC class I molecules. • Cytoplasmic transduction peptide facilitates the internalization of antigens to induce cross-presentation. • CTP-mediated dendritic cell vaccination promotes a vigorous specific T-cell response through cross-presentation. [ABSTRACT FROM AUTHOR]

Developing potent and durable heterogeneous catalysts is pivotal for advancing the implementation of the advanced oxidation processes in wastewater remediation. Herein, the "alloy" networks which were fabricated by incorporating zeolitic imidazolate framework-67 (ZIF-67) into porous organic polymers (POPs) matrix, was demonstrated, following pyrolyzed to prepare a core-shell Co@N-doped carbon-based catalyst (Co@NC-HBPC). The catalytic activity of Co@NC-HBPC for peroxymonosulfate (PMS) was regulated by modulating the preferential cobalt facet orientation, which in turn could be modulated by adapting the incorporation of ZIF-67. The as-prepared Co@NC-HBPC showed desirable Co dispersion, high catalytic reactivity (over 97 % degradation of Nitenpyram (NTP) within 20 min), high stability (maintaining 89.8 % NTP oxidation in five cycles), and wide environmental adaptability towards Fenton-like reaction. Both quenching and probe experiments verified the dominant roles of hydroxyl radicals (•OH) and singlet oxygen (1O 2) species in NTP degradation process. Texture coefficient (TC) analysis and theoretical calculations unraveled that the Co (200) facet displayed the highest activity for PMS activation, which could modulate the surface electronic structure of N-doped carbon layer shell. This study provides comprehensive insights into the synergistic effect of metal facet and material morphology in PMS activation, thus offering new prospects for designing highly efficient heterogeneous catalysts for environmental remediation. [Display omitted] • Co@N-doped carbon catalyst derived from MOF-POP "alloy networks" was designed and synthesized. • ZIF-67 could modulate Co facets orientation and induce Co/N doping to shoot two hawks with one arrow. • The catalytic activity of Co@NC-HBPC could be regulated by modulating the preferential Co facets. [ABSTRACT FROM AUTHOR]

Narirutin, extracted from the dried ripe pericarp of Rutaceae orange and its cultivated varieties, is a dihydroflavone compound with various biological activities and pharmacological effects. So far as we know, the metabolism profiling of narirutin has been insufficient until now. In the present study, an efficient method was employed to perform rapid analysis and identification of narirutin metabolites by using ultra-high performance liquid chromatography quadrupole exactive orbitrap MS/MS (UHPLC-Q-Exactive Orbitrap MS/MS) combined with an analogous core recursion (ACR) analysis strategy. Firstly, according to the basic core structure of the dihydroflavonoid, the cleavage mode and fragmentation ions of narirutin were summarized. Secondly, based on the difference of the substituent groups, the fragment ions of narirutin were preliminarily inferred and verified by the secondary mass spectra of its standard compound. Thirdly, the fragment ions of narirutin in positive and negative ion modes were summarized to provide a basis for the identification of metabolites. Fourthly, candidate metabolites were accurately and tentatively identified according to the cleavage law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic fragment ion clusters (DFICs) and characteristic suggestive ions (CSIs) deduced preliminarily. Finally, a total of 46 metabolites (30 in vivo and 19 in vitro), including prototype drugs were identified based on the ACR analysis strategy, chromatographic retention behavior of metabolites, corresponding Clog P value and accurate molecular weight. Among them, 22 metabolites were discovered in rats plasma, 12 in urine, 4 in liver tissue, 19 in liver microsomes, respectively. Additionally, metabolites relative contents were also studied by extracted ion chromatography (EIC) method. Our result also illustrated that narirutin primarily underwent glucuronidation, sulfation, glutathione binding, deglycosylation, oxidation, reduction, methylation, hydroxylation, ring-opening and their composite reactions. A novel strategy was constructed to comprehensively elucidate the biotransformation pathways of narirutin in vitro and in vivo , and a systematic metabolic profile of narirutin was generated. This study provided a great reference for further understanding of the biotransformation pathways and guiding for clinical application of narirutin. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a very rare tumor of increasing incidence. It is often misdiagnosed due to the unspecific presentation or unavailable biopsy, and results in poor prognosis. PCNSL involved the spinal cord is extremely sparse. Here we report a gentleman presented with one-year history of progressive tremor in the left limbs and slight dysarthria as well as three-month history of paraparesis, tinnitus and insomnia. MR images disclosed the swollen cerebellum and cauda equine, with contrast enhancement in both meninges and nerve roots. The cerebrospinal fluid (CSF) revealed extremely high protein level. Tubercular meningitis was considered and anti-tuberculosis therapy was given for weeks but without relief. With progressive deterioration, the PCNSL was eventually presumed according to positive CSF cytology and exclusion of systemic involvement. However, the patient passed away within days. We then reviewed the current diagnostic methods of PCNSL. The biopsy, as the gold standard for PCNSL diagnosis, is not eligible for all patients suspected PCNSL. The presurgical diagnostic algorithm of PCNSL has been fixed by clinicians and we suggest the early and repeated CSF cytology should be included for definitive diagnosis. [ABSTRACT FROM AUTHOR]

Previous studies have shown that melatonin can protect cells against rotenone-induced cell death. Yet, the mechanism involved in this protection requires further research. In this study, we aimed to further investigate the effects of melatonin on inhibiting rotenone-induced SH-SY5Y cells and the underlying molecular mechanisms. Human neuroblastoma SH-SY5Y cells were treated with 0.3 or 1 μM rotenone for 6 or 12 h. Cell viability was measured with an MTS assay, the mitochondrial membrane potential was determined with a Rhodamine 123 staining assay, and the protein expression levels of the markers of autophagy, including cytochrome C release (Cyt C), light chain 3B (LC3 B) and Dynamin-Related Protein 1 (Drp1) were analyzed by western blotting. The co-localization of Drp1 and TOM20 proteins in the mitochondria of SH-SY5Y cells was measured by immunofluorescence coupled with confocal microscopy and the overexpression of the Drp1 gene was then conducted. The viability and expression levels of Cyt C and LC3 B in rotenone and melatonin + rotenone-treated Drp1-overexpressed SH-SY5Y cells were analyzed with MTS and western blotting, respectively. We found that rotenone effectively induced SH-SY5Y cell death by causing mitochondrial dysfunction and increasing Cyt C expression. Drp1 expression and its regulation of mitochondrial translocation mediated the rotenone-induced cell death and melatonin inhibited this process. Overexpression of Drp1 protein attenuated melatonin's inhibition of rotenone-induced SH-SY5Y cell death. In conclusion, melatonin effectively inhibits rotenone-induced neuronal cell death via the regulation of Drp1 expression. [ABSTRACT FROM AUTHOR]

This study was designed to synthesize a functionalized chitosan by coupling the amine groups of chitosan with 2,4,6-Trimethoxybenzaldehyde, producing a chitosan Schiff base (Cs-TMB). The development of Cs-TMB was verified employing FT-IR, 1H NMR, the electronic spectrum, and elemental analysis. Antioxidant assays exhibited significant ameliorations of Cs-TMB, reporting scavenging activities of 69.67 ± 3.48 % and 39.65 ± 1.98 % for ABTS•+ and DPPH, respectively, while native chitosan showed scavenging ratios of 22.69 ± 1.13 % and 8.24 ± 0.4.1 % toward ABTS•+ and DPPH, respectively. Besides, Cs-TMB exerted significant antibacterial activity up to 90 % with remarkable bactericidal capacity against virulent gram-negative and gram-positive bacteria compared to the original chitosan. Furthermore, Cs-TMB exhibited a safe profile against normal fibroblast cells (HFB4). Interestingly, flow cytometric analysis showed that Cs-TMB demonstrated prominent anticancer properties of 52.35 ± 2.99 % against human skin cancer cells (A375), compared to 10.66 ± 0.55 % for Cs-treated cells. Moreover, Python and PyMOL in-house scripts were used to predict the interaction of Cs-TMB with the adenosine A1 receptor and visualized as a protein-ligand system submerged in a lipid membrane. Overall, these findings accentuate that Cs-TMB could be a favorable representative for wound dressing formulations and skin cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Efficient and feasible removal of trace antibiotics from wastewater is extremely important due to its environmental persistence, bioaccumulation, and toxicity, but still remains a huge challenge. Herein, three natural phenol-inspired porous organic polymers were fabricated from natural phenolic-derived monomers (p -hydroxy benzaldehyde, 2,4-dihydroxy benzaldehyde and 2,4,6-trihydroxy benzaldehyde) and melamine via polycondensation reaction. Characterization highlighted that the increasing contents of hydroxyl groups in monomers induced an increase of the polymer total porosity and promoted the formation of a highly microporous structure. With mesopore-dominated pore (average pore diameter 9.6 nm) and large pore volume (1.78 cm3/g), p -hydroxy benzaldehyde-based porous polymer (1-HBPP) exhibited ultra-high maximum adsorption capacity (q max) of 697.6 mg/g for tetracycline (TC) antibiotic. Meanwhile, the porous networks and plentiful active sites of 1-HBPP enabled fast adsorption kinetics (within 10 min) for TC removal, which could be well described by the pseudo-second-order model. Dynamic adsorption studies showed that 1-HBPP could be used in fixed-bed adsorption column (FBAC) with high removal efficiency (breakthrough volume per unit mass, 13.2 L/g) and dynamic adsorption capacity (201.6 mg/g), which were much higher than other reported adsorbents. The breakthrough curves both well matched with Thomas and Yoon-Nelson models in FBAC treatment. Moreover, removal mechanism analysis affirmed that pore-filling, hydrogen bonding, electrostatic interactions and π-π stacking interactions were main driving forces for TC adsorption. The prepared natural phenol-inspired porous adsorbents show great potential in antibiotics removal from wastewater, and this strategy would promote the sustainable and high-value utilization of natural phenolic compounds. [Display omitted] • Natural phenol-inspired polymers were fabricated within high porosity properties. • 1-HBPP exhibited excellent removal ability towards tetracycline antibiotics both in static and dynamic adsorption. • Synergistic adsorption mechanism was responsible for high removal abilities. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that annonaceous acetogenin (AA) was an antitumor drug with anti-angiogenic activity. However, the effect of AA on ocular neovascular disorders remains unclear. The aim of the present study is to explore the effect of AA092, an annonaceous acetogenin mimetic, on corneal neovascularization (CNV). In a mouse model of alkali-induced CNV, topical application of AA092 to the injured corneas attenuated CNV. In addition, in vivo treatment with AA092 down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1, EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, AA092 inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that AA092 has therapeutic potential for angiogenesis-associated diseases such as CNV. [ABSTRACT FROM AUTHOR]

The discovery of induced pluripotent stem cells (iPSCs) and the rapid evolution of clinically compliant protocols to generate such lines from a variety of tissue sources has raised the possibility that personalized medicine may be achievable in the near future. Several strategies to deliver iPSCs for iPSC-derived cell-based therapy have been proposed: one such model has been the cell-banking model, using processes developed by the cord blood industry. The cord blood industry has evolved primarily as a banking model in which units of cord blood harvested from discarded placenta are stored either in a public or a private cord blood bank for future use. The consideration of a cord blood--like banking model has been further spurred by the realization that this population of cells is an ideal starting sample to generate pluripotent cells. Spurred by these technological advances, major efforts are underway to develop a current Good Manufacturing Practice--compliant protocol to generate iPSCs from cord blood and to develop a haplobanking strategy. In this article, we discuss the issues that may affect such an effort. [ABSTRACT FROM AUTHOR]

Summary Parkinson’s disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation ( GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and nongenetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of “footprint-free” iPSC-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ∼50% GBA enzymatic activity, ∼3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment with MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) regulate gene transcription by modifying the acetylation level of histone and nonhistone proteins. In this study, we examined the effect of largazole, an inhibitor of class I HDACs, on inflammatory corneal angiogenesis. In a mouse model of alkali-induced corneal neovascularization (CNV), topical application of largazole to the injured corneas attenuated CNV. In addition, in vivo treatment with largazole down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1 and EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, largazole inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that largazole has therapeutic potential for angiogenesis-associated diseases. [ABSTRACT FROM AUTHOR]

Interleukin-1β (IL-1β) is a potent proinflammatory cytokine that plays a critical role in initiating immunoinflammatory responses. In this study, we generated recombinant mouse IL-1β and anti-mouse IL-1β polyclonal antibodies to examine the effect of IL-1β on experimental autoimmune uveoretinitis (EAU), a mouse model for T cell-mediated eye autoimmune disease. Administration of mouse IL-1β by i.p. in the priming phase, but not in the effector phase, of immune response of EAU enhanced disease scores and its related immune responses including DTH, Ag-specific T cell proliferation and the production of IL-17 and IFN-γ. Furthermore, administration of anti-IL-1β antibody in the priming phase reduced EAU scores. These results suggest that IL-1β is an important mediator in the pathogenesis of autoimmune diseases such as uveitis. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin-1β (IL-1β) belongs to IL-1 family and is a potent pro-inflammatory cytokine. It is known to be also involved in a variety of cellular activities, including cell proliferation, differentiation and apoptosis. In addition to its pathophysiologic role in host protection, IL-1β promotes the progression of a number of autoimmune diseases. Most of such diseases can be controlled by anti-IL-1β treatment. This review discusses the contribution of IL-1β to the course of autoimmune diseases, such as rheumatic diseases, uveitis, autoimmune thyroid diseases (AITD), insulin-dependent diabetes mellitus (IDDM), autoimmune inner ear disease (AIED), multiple sclerosis (MS), myocarditis, hepatitis and kidney diseases. The critical involvement of IL-1β in the pathogenesis of autoimmune diseases provides targets for developing therapeutic treatment. [Copyright &y& Elsevier]