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Immune evasion and metabolism reprogramming have been regarded as two vital hallmarks of the mechanism of carcinogenesis. Thus, targeting the immune microenvironment and the reprogrammed metabolic processes will aid in developing novel anti-cancer drugs. In recent decades, herbal medicine has been widely utilized to treat cancer through the modulation of the immune microenvironment and reprogrammed metabolic processes. However, labor-based herbal ingredient screening is time consuming, laborious and costly. Luckily, some computational approaches have been proposed to screen candidates for drug discovery rapidly. Yet, it has been challenging to develop methods to screen drug candidates exclusively targeting specific pathways, especially for herbal ingredients which exert anti-cancer effects by multiple targets, multiple pathways and synergistic ways. Meanwhile, currently employed approaches cannot quantify the contribution of the specific pathway to the overall curative effect of herbal ingredients. Hence, to address this problem, this study proposes a new computational framework to infer the contribution of the immune microenvironment and metabolic reprogramming (COIMMR) in herbal ingredients against human cancer and specifically screen herbal ingredients targeting the immune microenvironment and metabolic reprogramming. Finally, COIMMR was applied to identify isoliquiritigenin that specifically regulates the T cells in stomach adenocarcinoma and cephaelin hydrochloride that specifically targets metabolic reprogramming in low-grade glioma. The in silico results were further verified using in vitro experiments. Taken together, our approach opens new possibilities for repositioning drugs targeting immune and metabolic dysfunction in human cancer and provides new insights for drug development in other diseases. COIMMR is available at https://github.com/LYN2323/COIMMR.
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Antineoplásicos , Neoplasias , Plantas Medicinais , Humanos , Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Linfócitos T , Medicina Herbária , Microambiente TumoralRESUMO
As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle "undruggable" targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.
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Quimera de Direcionamento de Proteólise , Humanos , Cinética , MutaçãoRESUMO
Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.
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Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Descoberta de Drogas/métodos , RetroalimentaçãoRESUMO
The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.
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Quitosana , Doxorrubicina , Liberação Controlada de Fármacos , Glutationa , Hidrogéis , Nanoestruturas , Peptídeos , Hidrogéis/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Quitosana/química , Glutationa/química , Peptídeos/química , Humanos , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Concentração de Íons de HidrogênioRESUMO
The photochemistry of noncovalent interactions to promote organic transformations is an emerging approach to providing fresh opportunities in synthetic chemistry. Generally, the external substance is necessary to add as an interaction partner, thereby sacrificing the atom economy of the reaction. Herein, we describe a catalyst-free and noncovalent interaction-mediated strategy to access the olefination of N-tosylhydrazones using acetone as a solvent and an interaction partner. This protocol also features broad substrate scope, excellent functional group compatibility, and mild reaction conditions without transition metals. Moreover, the gram-scale synthesis of olefins and the generation of pharmaceutical intermediates highlighted its practical applicability. Lastly, mechanistic studies indicate that the reaction was initiated via noncovalent interactions between acetone and N-tosylhydrazone anion, which is also supported by density functional theory calculations.
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Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.
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Antibacterianos , Escherichia coli , Células Endoteliais da Veia Umbilical Humana , Hidrogéis , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Nanofibras , Peptídeos , Prata , Staphylococcus aureus , Prata/química , Prata/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Escherichia coli/efeitos dos fármacos , Nanofibras/química , Humanos , Peptídeos/química , Peptídeos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Cicatrização/efeitos dos fármacosRESUMO
Amphiphilic peptides have garnered significant attention due to their highly designable and self-assembling behaviors. Self-assembled peptides hold excellent potential in various fields such as biosensing, environmental monitoring, and drug delivery, owing to their remarkable biological, physical, and chemical properties. While nanomaterials formed by peptide self-assembly have found widespread use in biomedical applications, the development of 2D peptide nanosheets based on the self-assembly of amphiphilic peptides remains challenging in terms of rational design and morphology modulation. In this study, rationally designed amphiphilic peptide molecules are self-assembled into peptide nanosheets (PNS) under specific conditions to encapsulate gold nanoparticles (AuNPs), resulting in the formation of AuNPs/PNS hybrid materials with high photothermal conversion efficiency. The findings demonstrate that 2D PNS enhances the overall photothermal therapy effect of the nanohybrid materials due to their larger hosting area for AuNPs and higher biocompatibility. The well-designed amphiphilic peptides in this study offer insights into the structural design and functional modulation of self-assembled molecules. In addition, the constructed biomimetic-functional 2D inorganic/organic nanohybrid materials hold potential applications in biomedical engineering.
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Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Like cancer cells, immune cells within the tumor microenvironment or premetastatic niche also undergo extensive metabolic reprogramming, which profoundly impacts anti-tumor immune responses. Numerous evidence has illuminated that immunosuppressive TME and the metabolites released by tumor cells, including lactic acid, Prostaglandin E2 (PGE2), fatty acids (FAs), cholesterol, D-2-Hydroxyglutaric acid (2-HG), adenosine (ADO), and kynurenine (KYN) can contribute to CD8+ T cell dysfunction. Dynamic alterations of these metabolites between tumor cells and immune cells can similarly initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response. This review summarizes the new landscape beyond the classical metabolic pathways in tumor cells, highlighting the pivotal role of metabolic disturbance in the immunosuppressive microenvironment, especially how nutrient deprivation in TME leads to metabolic reprogramming of CD8+ T cells. Likewise, it emphasizes the current therapeutic targets or strategies related to tumor metabolism and immune response, providing therapeutic benefits for tumor immunotherapy and drug development in the future. Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Dynamic alterations of metabolites between tumor cells and immune cells initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response.
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An abnormal level of dopamine (DA), a kind of neurotransmitter, correlates with a series of diseases, including Parkinson's disease, Willis-Ekbom disease, attention deficit hyperactivity disorder, and schizophrenia. Hence, it is imperative to achieve a precise, rapid detection method in clinical medicine. In this study, we synthesized nanocomposite carbon aerogels (CAs) doped with iron and iron carbide, based on algae residue-derived biomass materials, using Fe(NO3)3 as the iron source. The modified glassy carbon electrode (GCE) for DA detection, denoted as CAs-Fe/GCE, was prepared through surface modification with this composite material. X-ray photoelectron spectroscopy and X-ray diffraction characterization confirmed the successful doping of iron into the as-prepared CAs. Additionally, the electrochemical behavior of DA on the modified electrode surface was investigated and the results demonstrate that the addition of the CAs-Fe promoted the electron transfer rate, thereby enhancing their sensing performance. The fabricated electrochemical DA biosensor exhibits an accurate detection of DA in the concentration within the range of 0.01~200 µM, with a detection limit of 0.0033 µM. Furthermore, the proposed biosensor is validated in real samples, showing its high applicability for the detection of DA in beverages.
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Técnicas Biossensoriais , Carbono , Dopamina , Técnicas Eletroquímicas , Eletrodos , Ferro , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Dopamina/análise , Dopamina/química , Carbono/química , Ferro/química , Técnicas Eletroquímicas/métodos , Géis/química , Limite de Detecção , Espectroscopia Fotoeletrônica , Nanocompostos/químicaRESUMO
Leucine-rich repeat extensins (LRXs) are required for plant growth and development through affecting cell growth and cell wall formation. LRX gene family can be classified into two categories: predominantly vegetative-expressed LRX and reproductive-expressed PEX. In contrast to the tissue specificity of Arabidopsis PEX genes in reproductive organs, rice OsPEX1 is also highly expressed in roots in addition to reproductive tissue. However, whether and how OsPEX1 affects root growth is unclear. Here, we found that overexpression of OsPEX1 retarded root growth by reducing cell elongation likely caused by an increase of lignin deposition, whereas knockdown of OsPEX1 had an opposite effect on root growth, indicating that OsPEX1 negatively regulated root growth in rice. Further investigation uncovered the existence of a feedback loop between OsPEX1 expression level and GA biosynthesis for proper root growth. This was supported by the facts that exogenous GA3 application downregulated transcript levels of OsPEX1 and lignin-related genes and rescued the root developmental defects of the OsPEX1 overexpression mutant, whereas OsPEX1 overexpression reduced GA level and the expression of GA biosynthesis genes. Moreover, OsPEX1 and GA showed antagonistic action on the lignin biosynthesis in root. OsPEX1 overexpression upregulated transcript levels of lignin-related genes, whereas exogenous GA3 application downregulated their expression. Taken together, this study reveals a possible molecular pathway of OsPEX1mediated regulation of root growth through coordinate modulation of lignin deposition via a negative feedback regulation between OsPEX1 expression and GA biosynthesis.
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Arabidopsis , Oryza , Giberelinas/farmacologia , Giberelinas/metabolismo , Oryza/metabolismo , Lignina/metabolismo , Proteínas/genética , Arabidopsis/genética , Parede Celular/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the "occupancy-driven" model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.
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Neoplasias Gástricas , Humanos , Crizotinibe/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteólise , Quimera de Direcionamento de Proteólise , Neoplasias Gástricas/tratamento farmacológico , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Functional nanomaterials as nanodrugs based on the self-assembly of inorganics, polymers, and biomolecules have showed wide applications in biomedicine and tissue engineering. Ascribing to the unique biological, chemical, and physical properties of peptide molecules, peptide is used as an excellent precursor material for the synthesis of functional nanodrugs for highly effective cancer therapy. Herein, recent progress on the design, synthesis, functional regulation, and cancer bioimaging and biotherapy of peptide-based nanodrugs is summarized. For this aim, first molecular design and controllable synthesis of peptide nanodrugs with 0D to 3D structures are presented, and then the functional customization strategies for peptide nanodrugs are presented. Then, the applications of peptide-based nanodrugs in bioimaging, chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) are demonstrated and discussed in detail. Furthermore, peptide-based drugs in preclinical, clinical trials, and approved are briefly described. Finally, the challenges and potential solutions are pointed out on addressing the questions of this promising research topic. This comprehensive review can guide the motif design and functional regulation of peptide nanomaterials for facile synthesis of nanodrugs, and further promote their practical applications for diagnostics and therapy of diseases.
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Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Peptídeos/química , Nanoestruturas/química , Terapia Biológica , Nanopartículas/uso terapêutico , Nanopartículas/químicaRESUMO
Biomimetic synthesis provides potential guidance for the synthesis of bio-nanomaterials by mimicking the structure, properties and functions of natural materials. Behavioral studies of biological surfaces with specific micro/nano structures are performed to explore the interactions of various molecules or organisms with biological surfaces. These explorations provide valuable inspiration for the development of biomimetic surfaces with similar effects. This work reviews some conventional preparation methods and functional modulation strategies for biomimetic interfaces. It aims to elucidate the important role of biomimetic interfaces with antifouling and low-pollution properties that can replace non-environmentally friendly coatings. Thus, biomimetic antifouling interfaces can be better applied in the field of marine antifouling and antimicrobial. In this review, the commonly used fabrication methods for biomimetic interfaces as well as some practical strategies for functional modulation is present in detail. These methods and strategies modify the physical structure and chemical properties of the biomimetic interfaces, thus improving the wettability, adsorption, drag reduction, etc. that they exhibit. In addition, practical applications are presented of various biomimetic interfaces for antifouling and look ahead to potential biomedical applications. By continuously discovering functional surfaces with biomimetic properties and studying their microstructure and macroscopic properties, more biomimetic interfaces will be developed.
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Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential of targeting undruggable pathogenic proteins. After the first proof-of-concept proteolysis-targeting chimeric (PROTAC) molecule was reported, the TPD field has entered a new era. In addition to PROTAC, numerous novel TPD strategies have emerged to expand the degradation landscape. However, their physicochemical properties and uncontrolled off-target side effects have limited their therapeutic efficacy, raising concerns regarding TPD delivery system. The combination of TPD and nanotechnology offers great promise in improving safety and therapeutic efficacy. This review provides an overview of novel TPD technologies, discusses their clinical applications, and highlights the trends and perspectives in TPD nanomedicine.
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Nanomedicina , Neoplasias , Humanos , Proteólise , Proteínas/metabolismo , Neoplasias/tratamento farmacológico , NanotecnologiaRESUMO
Breast cancer (BC) remains the foremost cause of cancer mortality globally, with neutrophils playing a critical role in its pathogenesis. As an essential tumor microenvironment (TME) component, neutrophils are emerging as pivotal factors in BC progression. Growing evidence has proved that neutrophils play a Janus- role in BC by polarizing into the anti-tumor (N1) or pro-tumor (N2) phenotype. Clinical trials are evaluating neutrophil-targeted therapies, including Reparixin (NCT02370238) and Tigatuzumab (NCT01307891); however, their clinical efficacy remains suboptimal. This review summarizes the evidence regarding the close relationship between neutrophils and BC, emphasizing the critical roles of neutrophils in regulating metabolic and immune pathways. Additionally, we summarize the existing therapeutic approaches that target neutrophils, highlighting the challenges, and affirming the rationale for continuing to explore neutrophils as a viable therapeutic target in BC management.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Neutrófilos/metabolismo , Resultado do Tratamento , Microambiente Tumoral , Ensaios Clínicos como AssuntoRESUMO
The mechanism of gallic acid in improving lipopolysaccharide-induced renal injury in rats was investigated by studying the pro-death and inflammatory response of cells. SPF rats were randomly divided into 4 groups with n=10 in each group. Blank control group: normal saline injection; The model group was injected with LPS induced model (LPS group); Low dose gallic acid group (LPS+L-GA group); Middle dose gallic acid group (LPS+M-GA group). The expression of serum inflammatory factors IL-1, IL-1ß, IL-18, and MCP-1 were detected by Elisa. Western blot assay was used to detect the expression of inflammation-related proteins. The contents of BUN, Scr, SUA, Serum cystatinALB, and ACR were determined by the biochemical analyzer. The pathological tissue sections were used to observe the kidney injury in each group. The renal expressions of NLRP3, Caspase-1, GSDMD, and IL-1ß were detected by immunohistochemistry. The activation of the AMPK/SIRT1 signaling pathway was detected by Western blot assay. The LPS-induced mouse kidney injury model was established successfully. Compared with the model group, different doses of gallic acid can improve the expression of renal biochemical indexes (P<0.05); At the same time, gallic acid can activate AMPK/SIRT1 and reduce kidney injury in mice (P<0.05); Compared with the model group, the expression of pyroptosis gene, the expression of genes related to inflammatory factors and the expression of inflammatory factors were decreased in the gallic acid injection group (P<0.05). By activating the AMPK/SIRT1 signaling pathway, gallic acid can inhibit the scorch death and validation effect in mice, thereby protecting the kidneys of mice.
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Lipopolissacarídeos , Sirtuína 1 , Ratos , Camundongos , Animais , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Proteínas Quinases Ativadas por AMP , RimRESUMO
Advanced metastatic colorectal cancers (CRCs) are regarded as a challenge in clinical cancer therapy. Our previous studies have demonstrated that a representative fluoro-substituted indole-chalcone (FC116), was obtained to display highly potent activity against CRC using multiple in vitro and in vivo mouse models by targeting microtubules. However, several problems, such as low dose tolerance and highly toxic to the brain and colon, low solubility unsuitable for intravenous (i.v.) administration, are still existed and limit further development. Herein, we developed two series of FC116 derivatives on the 4-methoxyphenyl group by a structure-based design strategy. Among them, FC11619 with an amino terminus maintained the in vitro cytotoxicity against HCT-116 CRC in a low nanomolar range. This compound could induce G2/M phase arrest via regulating cyclin B1 expression, produce excess reactive oxygen species (ROS), and target tubulin in CRC cells. In vivo, FC11619 significantly suppressed tumor growth, achieving 65.3 and 73.4 % at doses of 5 and 10 mg/kg/d (i.v., 21 d), which were much better than 54.1% of Taxol at 7 mg/kg. In addition, this compound showed better in vivo tolerance compared to that of FC116 (only 3 mg/kg tolerance, intraperitoneal, i.p.), and no major organ-related toxicity, especially no apparent degenerated neurons, intestinal obstruction in clinical Taxol standard therapy. Taken together, the 4-amino-substitutedphenyl indole-chalcones represent lead compounds as chemotherapy of CRC for further drug development in this field.
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Antineoplásicos , Chalcona , Chalconas , Neoplasias Colorretais , Animais , Camundongos , Chalcona/farmacologia , Chalcona/uso terapêutico , Chalconas/farmacologia , Chalconas/uso terapêutico , Chalconas/química , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Neoplasias Colorretais/tratamento farmacológico , Paclitaxel/farmacologia , Indóis/farmacologia , Indóis/uso terapêutico , Indóis/química , Proliferação de Células , Linhagem Celular Tumoral , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.
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Nanopartículas , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Humanos , Biomassa , HidrogéisRESUMO
This study describes the development of a long-range hybrid autonomous underwater vehicle (AUV) for ocean turbulence measurement. It is a unique instrument, combining the characteristics of the conventional AUV and the buoyancy-driven glider, with a variety of flexible motion modes, such as cruise mode, glider mode, drift mode, and combination of multiple motion modes. The hybrid AUV was used for continuous turbulence measurement in the continental slope of the northern South China Sea in 2020. A total of ten continuous profiles were completed covering a horizontal span of 25 Km and a depth of 200 m. The hybrid AUV was operated in the combined glider and cruise mode. The hybrid AUV's flight performance was stable and satisfied the requirement for turbulence observation. The measured velocity shears from both probes were in good agreement, and the noise-reduced shear spectra were in excellent agreement with the Nasmyth spectrum. The water column in the study area was highly stratified, with a thick thermocline. The dissipation rate (ε) varied from 1.41 × 10-10 to 4.18 × 10-7 W·kg-1. In the surface mixed layer, high values of ε (10-9â¼10-8 W·kg-1) were observed toward the water surface. In the thermocline, ε was 10-9.5â¼10-9 W·kg-1, which was smaller than the level of the surface mixed layer. This result was mainly because of the strong "barrier"-like thermocline, which damped the transmission of wind and heat energy from the surface mixed layer to the deep layer. Overall, this study demonstrates the utility of hybrid AUVs for collecting oceanic turbulence measurements. They are a powerful addition to traditional turbulence instruments, as they make it possible to survey large areas to obtain high-quality and high-resolution data in both vertical and horizontal directions over long durations.
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Scene text recognition (STR) has been a hot research field in computer vision, aiming to recognize text in natural scenes using computers. Currently, attention-based encoder-decoder frameworks struggle to precisely align feature regions with the target object when dealing with complex and low-quality images, a phenomenon known as attention drift. Additionally, with the rise of Transformer, the increasing size of parameters results in higher computational costs. In order to solve the above problems, based on the latest research results of Vision Transformer (ViT), we utilize an additional position-enhancement branch to alleviate attention drift and dynamically fused position information with visual information to achieve better recognition accuracy. The experimental results demonstrate that our model achieves a 3% higher average recognition accuracy on the test set compared to the baseline. Meanwhile, our model maintains the advantage of a small number of parameters and fast inference speed, achieving a good balance between accuracy, speed, and computational load.