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Biothiols play essential roles in maintaining normal physiological functions, resisting oxidative stress, and protecting cell health. Establishing an effective and reliable sensor array for the accurate quantification and discrimination of diverse biothiols is extremely meaningful. In this work, Ag/Mn3O4, Ag3PO4, and Ag3Cit with excellent oxidase-mimetic activity and surface-enhanced Raman scattering (SERS)-enhanced features have been prepared and loaded onto Whatman filter paper (WFP) to build SERS paper chips as three sensing channels, which can induce 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to SERS-active reporters (TMBox) and concurrently generate prominent SERS signals. Nevertheless, the addition of biothiols can suppress conversion from TMB to TMBox, which can cause the reduction of the SERS signal from TMBox. Interestingly, each SERS sensing channel can generate different TMBox signals' variations due to differences in the oxidative inhibition abilities of diverse biothiols and exclusive properties of each paper chip, which can be plotted as specific fingerprint patterns of each biothiol and further translated into intuitive two-dimensional (2D) clustering profiles through linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) techniques for precise identification of these six biothiols with the minimum concentration of 1 µM. More importantly, this SERS sensor array is exploited for the precise quantification of intracellular glutathione (GSH), and can differentiate between normal and cancer cells based on different intracellular GSH contents and even identify different types of tumor cells, demonstrating its powerful application prospects in disease diagnosis.
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Papel , Prata , Análise Espectral Raman , Compostos de Sulfidrila , Análise Espectral Raman/métodos , Humanos , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/química , Prata/química , Nanopartículas Metálicas/química , Propriedades de Superfície , Nanoestruturas/química , Oxirredução , Benzidinas/química , Linhagem Celular TumoralRESUMO
A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.
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Antibacterianos , Diterpenos , Testes de Sensibilidade Microbiana , Pleuromutilinas , Compostos Policíclicos , Triazóis , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Relação Estrutura-Atividade , Bactérias Gram-Positivas/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Escherichia coli/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Dose-Resposta a Droga , Descoberta de DrogasRESUMO
Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (â¼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.
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Quimioembolização Terapêutica , Doxorrubicina , Animais , Quimioembolização Terapêutica/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Coelhos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Suínos , Resinas Acrílicas/química , Polieletrólitos/química , Portadores de Fármacos/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/farmacocinética , Gelatina/química , Nanopartículas/química , Humanos , Liberação Controlada de Fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagemRESUMO
Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Cisteína , Corantes Fluorescentes , Análise de Alimentos , Peixe-Zebra , Corantes Fluorescentes/química , Animais , Cisteína/análise , Cisteína/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Camundongos , Humanos , Fígado/química , Fígado/metabolismoRESUMO
Unbonded flexible risers consist of several helical and cylindrical layers, which can undergo large bending deformation and can be installed in different configurations to adapt to harsh marine environments; thus, they can be applied to transport oil and gas resources from ultra-deep waters (UDW). Due to their special geometric characteristics, they can ensure sufficient axial tensile stiffness while having small bending stiffness, which can undergo large deflection bending deformation. In recent years, the development of unbonded flexible risers has been moving in an intelligent, integrated direction. This paper presents a review of unbonded flexible risers. Firstly, the form and properties of each interlayer of an unbonded flexible riser are introduced, as well as the corresponding performance and configuration characteristics. In recent years, the development of unbonded flexible risers has been evolving, and the development of machine learning on unbonded flexible risers is discussed. Finally, with emphasis on exploring the design characteristics and working principles, three new types of unbonded flexible risers, an integrated production bundle, an unbonded flexible riser with an anti-H2S layer, and an unbonded flexible riser with a composite armor layer, are presented. The research results show that: (1) the analytical methods of cross-sectional properties of unbonded flexible risers are solved based on ideal assumptions, and the computational accuracy needs to be improved. (2) Numerical methods have evolved from equivalent simplified models to models that account for detailed geometric properties. (3) Compared with ordinary steel risers, the unbonded flexible riser is more suitable for deep-sea resource development, and the structure of each layer can be designed according to the requirements of the actual environment.
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Implementing the concept of turning waste into treasure, the conversion of biomass waste into high-value carbon materials, especially carbon dots (CDs), has pointed out a new direction for disease diagnosis, tumor treatment, and other aspects. In this work, we have reported the GL-CDs(Fe) via a simple synthesis route exploiting Ganoderma lucidum waste as the precursor. Thanks to their excellent optical property and peroxidase mimetic activity, a novel GL-CDs(Fe)-based ratio fluorescence/colorimetric/smartphone triple mode sensing platform is cleverly fabricated for glucose determination with the LOD of 0.28, 0.37, and 0.52 µΜ separately. Especially, this triple mode biosensor is successfully utilized for glucose detection in serum samples with the relative error of less than ±8 % compared with clinical reports. Surprisingly, the GL-CDs(Fe) also presents immense application prospects in high-level anti-counterfeiting aspects due to their excellent luminescent properties, high water-solubility, and easy availability. Furthermore, GL-CDs(Fe) can catalyze excessive H2O2 inside tumor cells to produce massive hydroxyl radicals (·OH) which break down the redox levels of cancer cells and thereby eliminate tumor cells. Thus, this integrated "Three-in-One" multifunctional platform based on GL-CDs(Fe) unveils enormous research and application prospects for bio-sensing, anti-counterfeiting, cancer treatment.
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Técnicas Biossensoriais , Carbono , Ferro , Pontos Quânticos , Reishi , Carbono/química , Reishi/química , Humanos , Pontos Quânticos/química , Ferro/química , Técnicas Biossensoriais/métodos , Antineoplásicos/química , Antineoplásicos/farmacologia , Glucose/análise , Glucose/química , Glicemia/análise , Linhagem Celular Tumoral , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Colorimetria/métodos , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. RESULTS: lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. CONCLUSION: This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.
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Movimento Celular , Neoplasias Colorretais , Proteínas de Homeodomínio , MicroRNAs , RNA Longo não Codificante , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Endógeno Competitivo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn2+), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn2+ release inhibition properties. Benefiting from the regulated release of Zn2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli. The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.
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BACKGROUND: Seeking objective quantitative indicators is important for accurately recognizing major depressive disorder (MDD). Lempel-Ziv complexity (LZC), employed to characterize neurological disorders, faces limitations in tracking dynamic changes in EEG signals due to defects in the coarse-graining process, hindering its precision for MDD objective quantitative indicators. METHODS: This work proposed Adaptive Permutation Lempel-Ziv Complexity (APLZC) and Adaptive Weighted Permutation Lempel-Ziv Complexity (AWPLZC) algorithms by refining the coarse-graining process and introducing weight factors to effectively improve the precision of LZC in characterizing EEGs and further distinguish MDD patients better. APLZC incorporated the ordinal pattern, while False Nearest Neighbor and Mutual Information algorithms were introduced to determine and adjust key parameters adaptively. Furthermore, we proposed AWPLZC by assigning different weights to each pattern based on APLZC. Thirty MDD patients and 30 healthy controls (HCs) were recruited and their 64-channel resting EEG signals were collected. The complexities of gamma oscillations were then separately computed using LZC, APLZC, and AWPLZC algorithms. Subsequently, a multi-channel adaptive K-nearest neighbor model was constructed for identifying MDD patients and HCs. RESULTS: LZC, APLZC, and AWPLZC algorithms achieved accuracy rates of 78.29 %, 90.32 %, and 95.13 %, respectively. Sensitivities reached 67.96 %, 85.04 %, and 98.86 %, while specificities were 88.62 %, 95.35 %, and 89.92 %, respectively. Notably, AWPLZC achieved the best performance in accuracy and sensitivity, with a specificity limitation. LIMITATION: The sample size is relatively small. CONCLUSION: APLZC and AWPLZC algorithms, particularly AWPLZC, demonstrate superior effectiveness in differentiating MDD patients from HCs compared with LZC. These findings hold significant clinical implications for MDD diagnosis.
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Algoritmos , Transtorno Depressivo Maior , Eletroencefalografia , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Adulto , Feminino , Masculino , Processamento de Sinais Assistido por Computador , Pessoa de Meia-Idade , Estudos de Casos e Controles , Sensibilidade e EspecificidadeRESUMO
The extensive use of mineral fertilizers has a negative impact on the environment, whereas wastewater and microalgal biomass can provide crops with nutrients such as nitrogen, phosphorus, and potassium, and have the potential to be used as a source of fertilizers in circular agriculture. In this study, a step-by-step resource utilization study of algae-containing wastewater generated from microalgae treatment of swine wastewater was carried out. When wheat seedlings were cultivated in the effluent after microalgae separation, the root fresh weight, seedling fresh weight, and total seedling length were increased by 3.44%, 14.45%, and 13.64%, respectively, compared with that of the algae-containing wastewater, and there was no significant difference in seedling fresh weight, total seedling length, maximum quantum yields of PSII photochemistry (Fv/Fm), and performance index (PIABS) from that of the Hogland solution group, which has the potential to be an alternative liquid fertilizer. Under salt stress, microalgae extract increased the contents of GA3, IAA, ABA, and SA in wheat seedlings, antioxidant enzymes maintained high activity, and the PIABS value increased. Low-dose microalgae extract (1 mL/L) increased the root fresh weight, seedling fresh weight, longest seedling length, and total seedling length by 30.73%, 31.28%, 16.43%, and 28.85%, respectively. Algae extract can act as a plant biostimulant to regulate phytohormone levels to attenuate the damage of salt stress and promote growth.
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Biomassa , Microalgas , Plântula , Triticum , Águas Residuárias , Triticum/crescimento & desenvolvimento , Triticum/efeitos dos fármacos , Microalgas/crescimento & desenvolvimento , Microalgas/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Animais , Águas Residuárias/química , Suínos , Tolerância ao Sal , Fertilizantes/análise , Eliminação de Resíduos Líquidos/métodosRESUMO
Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.
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Antineoplásicos , Neoplasias , Animais , Camundongos , Emulsões/uso terapêutico , Acriflavina/farmacologia , Acriflavina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Quimioterapia Combinada , Hipóxia/tratamento farmacológicoRESUMO
The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL-1 and a detection limit of 3 cells mL-1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.
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Neoplasias das Glândulas Suprarrenais , Técnicas Biossensoriais , Células Neoplásicas Circulantes , Feocromocitoma , Humanos , Microfluídica , Sistemas Automatizados de Assistência Junto ao Leito , Feocromocitoma/diagnóstico , Smartphone , Dióxido de Silício/química , Células Neoplásicas Circulantes/patologia , Glucose , Neoplasias das Glândulas Suprarrenais/diagnóstico , Dispositivos Lab-On-A-ChipRESUMO
OBJECTIVE: The brain network serves as the physiological foundation for information processing of the brain. Many studies have reported abnormalities of gamma oscillations in Schizophrenia. The aim of this study was to investigate the gamma-band connectivity in Schizophrenia patients. METHODS: We recorded the resting state electroencephalogram (EEG) for 15 schizophrenia patients with refractory auditory hallucinations and 14 healthy controls, with eyes open and closed. The brain network was constructed based on weighted phase lag index for gamma band. Whole scalp metrics (clustering coefficient, global efficiency and local efficiency) and local region metrics (degree and betweenness centrality) in the frontal and temporal lobes were computed. Correlation analyses between network metrics and symptom scales were examined to find associations with symptom severity. RESULTS: Schizophrenia patients had larger global efficiency and local efficiency (p < 0.05) with eyes closed, probably representing greater brain activity and information exchange. For degree and betweenness centrality, schizophrenia patients showed an increase (p < 0.05) in the temporal lobe but a decrease (p < 0.05) in the frontal lobe with eyes closed and open, potentially account for the patients' symptoms such as hallucinations and thought disorders. Local efficiency and frontal lobe degree were positively and negatively correlated with the scales, respectively (both p < 0.05). CONCLUSIONS: Altered connectivity of the resting state brain network has been revealed and may be associated with the core symptoms of schizophrenia. Our study provides promising evidence for the investigation of the pathological basis of Schizophrenia and could aid in objective diagnosis.
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Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Eletroencefalografia , Encéfalo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Mapeamento Encefálico , Alucinações/diagnóstico por imagem , Alucinações/etiologiaRESUMO
Transarterial chemoembolization (TACE) is a common treatment for unresectable intermediate stage hepatocellular carcinoma (HCC) and involves the combination of chemotherapy agents and embolic materials to target and block the blood supply to the tumor, leading to localized treatment. However, the selection of clinical chemoembolization agents remains limited, and the effectiveness of various agents is still under investigation. Meanwhile, replicating the complex vasculature and extracellular matrix (ECM) circumstances of HCC in in vitro models for evaluating embolic agents proves to be challenging. Herein, we developed a decellularized cancerous liver model with translucent appearance, a complicated hepatic vascular system and tissue-specific ECM for the evaluation of embolic agents. Inkpad oil and microparticles were used to illustrate different systems of vascular structures between healthy and HCC rats' livers. Quantitative analysis with AngioTool revealed significant differences in vessel density and lacunarity between the two groups. Proteomics showed higher secretion of collagens in the HCC rat liver models than in healthy livers. Utilizing this in vitro model, we investigated the impact of tumor-specific vascular structure and ECM composition on chemoembolization performance, the two key factors inaccessible by currently available drug release testing platforms. Our findings revealed that the presence of an aberrant vascular system and the distorted ECM within the model led to drug retention. This preclinical model holds great promise as a valuable tool for evaluating embolic agents and studying their performance in the tumor microenvironment. STATEMENT OF SIGNIFICANCE: Transarterial chemoembolization (TACE), which employs drug-eluting embolic agents to obstruct the tumor-feeding vessels while locally releasing chemotherapeutic drugs into the tumor, has become the first-line treatment of unresectable liver cancer over past two decades. Nevertheless, the advancement of effective drug-eluting embolic agents has been retarded due to the lack of appropriate in vitro models for assessing the local embolization and chemotherapy performances in TACE. Here we developed a cirrhotic hepatocellular carcinoma-based decellularized liver cancer model, which preserves the aberrant vasculatures and tumor-specific extracellular matrix of liver cancer, for TACE evaluation. This model incorporates a blood flow simulation component to assess the dynamics of drug release behaviors of chemoembolic agents within tumor-mimicking conditions, more accurately replicating the in vivo environment for the locoregional assessments as compared to conventional in vitro models.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cirrose Hepática , Microambiente TumoralRESUMO
Background: Numerous clinical reports have suggested that psychopathy like schizophrenia, anxiety and depression is accompanied by early attentional abnormalities in emotional processing. Recently, the efficacy of transcranial alternating current stimulation (tACS) in changing emotional functioning has been repeatedly observed and demonstrated a causal relationship between endogenous oscillations and emotional processing. Aims: Up to now, tACS effects on emotional attention have not yet been tested. To assess such ability, we delivered active-tACS at individual alpha frequency (IAF), 10 Hz or sham-tACS for 7 consecutive days in the bilaterally dorsolateral prefrontal cortex (dlPFC) to totally 79 healthy participants. Results: IAF-tACS group showed significant alpha entrainment at-rest, especially in open state around stimulation area and showed an obvious advantage compared to 10 Hz-tACS. Event-related potential revealed a significant larger P200 amplitude after active-tACS and IAF group showed wider range of emotions than 10 Hz-tACS, indicating the attentional improvement in facial emotion processing. A notable positive correlation between alpha power and P200 amplitude provided an electrophysiological interpretation regarding the role of tACS in emotional attention modulation instead of somatosensory effects. Conclusion: These results support a seminal outcome for the effect of IAF-tACS on emotional attention modulation, demonstrating a feasible and individual-specific therapy for neuropsychiatric disorders related to emotion processing, especially regarding oscillatory disturbances.
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Postoperative sore throat (POST) is a prevalent complication after general anesthesia and targeting high-risk patients help in its prevention. This study developed and validated a machine learning model to predict POST. A total number of 834 patients who underwent general anesthesia with endotracheal intubation were included in this study. Data from a cohort of 685 patients was used for model development and validation, whilst a cohort of 149 patients served for external validation. The prediction performance of random forest (RF), neural network (NN), and XGBoost models was compared using comprehensive performance metrics. The Local Interpretable Model-Agnostic Explanations (LIME) methods elucidated the best-performing model. POST incidences across training, validation, and testing cohorts were 41.7%, 38.4%, and 36.2%, respectively. Five predictors were age, sex, endotracheal tube cuff pressure, endotracheal tube insertion depth, and the time interval between extubation and the first drinking of water after extubation. After incorporating these variables, the NN model demonstrated superior generalization capabilities in predicting POST when compared to the XGBoost and RF models in external validation, achieving an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI 0.74-0.89) and a precision-recall curve (AUPRC) of 0.77 (95% CI 0.66-0.86). The model also showed good calibration and clinical usage values. The NN model outperforms the XGBoost and RF models in predicting POST, with potential applications in the healthcare industry for reducing the incidence of this common postoperative complication.
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Background: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme in Children. Case Summary: A female patient aged 5.5 years with antiphospholipid syndrome (APS) was administered oral rivaroxaban tablets 2.5 mg twice a day for 16 days. Subsequently, the patient developed a slight itching sensation on both feet and buttocks without an apparent cause. The following day, erythema multiforme appeared across the body in a scattered pattern. The erythema presented higher than the skin surface and partially merged into areas of the skin. Following an increase in the extent and degree of the erythema, all oral medications were ceased. Treatment with dexamethasone sodium phosphate injection, mometasone furoate cream, and mucopolysaccharide polysulfate cream resulted in an improvement of erythema multiforme. The erythema diminished and did not deteriorate subsequent to changing from rivaroxaban tablets to warfarin sodium tablets, and receiving nadroparin calcium injection.
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BACKGROUND: To explore the potential role of m6A methylation modification in Wilms Tumor (WT) by m6A-RNA Methylation (m6A) regulators. METHODOLOGY: The association of m6A modification patterns with immune and prognostic characteristics of tumors was systematically evaluated using 19 m6A regulators extracted from Wilms Tumor's samples in public databases. A comprehensive model of "m6Ascore" was constructed using principal component analysis, and its prognostic value was evaluated. RESULTS: Almost all m6A regulators were differentially expressed between WT and normal tissues. Unsupervised clustering identified three distinct m6A clusters that differed in both immune cell infiltration and biological pathways. The m6Ascore was constructed to quantify m6A modifications in individual patients. Our analysis suggests that m6Ascore is an independent prognostic factor for WT and can be used as a novel predictor of WT prognosis. CONCLUSIONS: This study comprehensively explored and systematically characterized m6A modifications in WT. m6A modification patterns play a critical role in the tumor immune microenvironment (TIME) and WT prognosis. m6Ascore provides a more comprehensive understanding of m6A modifications in WT and offers a practical tool for predicting WT prognosis. This study will help clinicians to identify valid indicators of WT to improve the poor prognosis of this disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://www.aliyundrive.com/drive/folder/64be739cd6956a741fb24670baeea53422be6024 .
Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Metilação , Prognóstico , Tumor de Wilms/genética , Neoplasias Renais/genética , RNA , Microambiente TumoralRESUMO
Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.
Assuntos
Disfunção Cognitiva , Distúrbios do Início e da Manutenção do Sono , Humanos , Animais , Camundongos , Estudo de Associação Genômica Ampla , Proteômica , Disfunção Cognitiva/genética , SonoRESUMO
Background: Antimicrobial agents' wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients' families. Moreover, the cost of disposing of antimicrobial agents' waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients' expenditures, saving medical costs, and reducing drug proportion. Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children's Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed. Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499. Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients' payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.