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Polyolefin separators are the most commonly used separators for lithium batteries; however, they tend to shrink when heated, and their Li+ transference number (t Li +) is low. Metal-organic frameworks (MOFs) are expected to solve the above problems due to their high thermal stability, abundant pore structure, and open metal sites. However, it is difficult to prepare high-porosity MOF-based membranes by conventional membrane preparation methods. In this study, a high-porosity free-standing MOF-based safety separator, denoted the BCM separator, is prepared through a nano-interfacial supramolecular adhesion strategy. The BCM separator has a large specific surface area (450.22 m2 g-1) and porosity (62.0%), a high electrolyte uptake (475 wt%), and can maintain its morphology at 200 °C. The ionic conductivity and t Li + of the BCM separator are 1.97 and 0.72 mS cm-1, respectively. Li//LiFePO4 cells with BCM separators have a capacity retention rate of 95.07% after 1100 cycles at 5 C, a stable high-temperature cycling performance of 300 cycles at 80 °C, and good capacity retention at -40 °C. Li//NCM811 cells with BCM separators exhibit significantly improved rate performance and cycling performance. Pouch cells with BCM separators can work at 120 °C and have good safety at high temperature.
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PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.
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Meios de Contraste , Compostos Férricos , Ferro , Neoplasias Renais , Imageamento por Ressonância Magnética , Óxidos , Tomografia Computadorizada por Raios X , Ultrassonografia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia/métodos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Diagnóstico Diferencial , Adulto , Idoso de 80 Anos ou maisRESUMO
Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4â³,4â´-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.
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Antibacterianos , Complexos de Coordenação , Cobre , Nitrofuranos , Polímeros , Antibacterianos/química , Antibacterianos/análise , Ligantes , Nitrofuranos/análise , Nitrofuranos/química , Cobre/química , Cobre/análise , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Polímeros/química , Molibdênio/química , Piridinas/química , Estrutura Molecular , Técnicas Eletroquímicas , Modelos MolecularesRESUMO
To mimic natural photonic crystals having color regulation capacities dynamically responsive to the surrounding environment, periodic assembly structures have been widely constructed with response materials. Beyond monocomponent materials with stimulus responses, binary and multiphase systems generally offer extended color space and complex functionality. Constructing a rule for predicting response sensitivity can provide great benefits for the tailored design of intelligently responsive photonic materials. Here, we elucidate mathematical relationships between the response sensitivity of dynamically structural-color changes and the location distances of photonic co-phases in three-dimensional Hansen space that can empirically express the strength of their interaction forces, including dispersion force, polarity force, and hydrogen bonding. Such an empirical rule is proven to be applicable for some typical alcohols, acetone, and acetic acid regardless of their molecular structures, as verified by angle resolution spectroscopy, in situ infrared spectroscopy, and molecular simulation. The theoretical method we demonstrate provides rational access to custom-designed responsive structural coloration.
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More and more attention has been paid to the development of the efficient electrocatalysts for the oxygen evolution reaction (OER). Herein, a porous vanadic oxide-doped cobalt pyrophosphate electrocatalyst, namely V2O5-Co2P2O7, was exploited by using the electrochemical reconstruction method in the alkaline electrolyte and selecting a cobalt vanadium phosphate Co(H2O)4(VOPO4)2 as a precursor. The reconstructed vanadic oxide-doped cobalt pyrophosphate catalyst V2O5-Co2P2O7 exhibited efficient electrocatalytic activity for the OER in 1.0 M KOH, requiring a low overpotential of 199 mV at 10 mA cm-2, compared to the reported pyrophosphate electrocatalysts. The porous morphology and doping of vanadic oxide after electrochemical reconstruction were beneficial to enhance the electrocatalytic performance for the OER, through improving the surface area to bring in more accessibly active sites and regulating the electronic structures. The results provided a promising strategy to prepare the pyrophosphate electrocatalysts and improve the performance of the OER catalyst.
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BACKGROUND: It is difficult to preserve the structure and microbial distribution inside comedonal plugs during routine processing. OBJECTIVE: The objective of this study is to determine the optimal method to preserve the comedonal corneum plug structure and inherent microorganisms thereby eliminating the need to perform punch biopsies in relevant studies. METHODS: Corneum plugs were extracted from comedones of acne vulgaris patients. Primary embedding using either a 2% agarose, 2% agar, 25% gelatin, or 2% agar + 2.5% gelatin solution was subsequently performed and the results compared. The specimens were then fixed, waxed, sectioned, and examined by light, fluorescence, and scanning electron microscopies to observe the structures and microorganisms within the plugs. RESULTS: Both the 25% gelatin and 2% agarose solutions successfully preserved the structural integrity of corneum plugs and the inherent microorganisms. When considering other factors such as thermostability, reusability, and convenience, the 25% gelatin solution was the superior choice among the four materials. CONCLUSION: We report a simple and effective method for double embedding comedonal plugs and other small tissue specimens. The technique preserves the structure and microbial distribution in situ within comedonal corneum plugs, eliminates the need for punch biopsies. This method may also be applied to other tiny and fragile tissue specimens, thereby enabling a potentially wide array of future large-scale investigations and alleviated patients' pain.
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Acne Vulgar , Gelatina , Humanos , Ágar , Sefarose , Acne Vulgar/tratamento farmacológico , BiópsiaRESUMO
BACKGROUND: Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty. METHODS: We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications. RESULTS: There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups. CONCLUSION: IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022; https://www.chictr.org.cn/searchprojEN.html ).
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Artroplastia de Quadril , Bloqueio Nervoso , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides , Nervo Femoral , Bloqueio Nervoso/métodos , Artroplastia de Quadril/efeitos adversos , AnalgésicosRESUMO
The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone â ¡_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-â ¢ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
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Ácido Glicirretínico , Lipossomos , Humanos , Células Estreladas do Fígado , Ácido Glicirretínico/farmacologia , Fígado , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Colágeno/farmacologiaRESUMO
A novel in situ chemical upcycling strategy for plastic waste is proposed by the customized diphenylacetylene monomer with dual photo-response. That is, diphenylacetylene reactive monomers are in situ inserted into the macromolecular chain of polyethylene terephthalate (PET) plastics/fibers through one-pot transesterification of slight-depolymerization and re-polymerization. On the one hand, the diphenylacetylene group absorbs short-wave high-energy UV rays and then releases long-wave low-energy harmless fluorescence. On the other hand, the UV-induced photo-crosslinking reaction among diphenylacetylene groups produces extended π-conjugated structure, resulting in a red-shift (due to decreased HOMO-LUMO separation) in the UV absorption band and locked crosslink points between PET chains. Therefore, with increasing UV exposure time, the upcycled PET plastics exhibit reverse enhanced UV resistance and mechanical strength (superior to original performance), instead of serious UV-photodegradation and damaged performance. This upcycling strategy at oligomer-scale not only provides a new idea for traditional plastic recycling, but also solves the common problem of gradual degradation of polymer performance during use.
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Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.
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Variações do Número de Cópias de DNA , Tetralogia de Fallot , Povo Asiático/genética , Moléculas de Adesão Celular/genética , DNA , Variações do Número de Cópias de DNA/genética , Proteínas Ligadas por GPI/genética , Estudo de Associação Genômica Ampla , Humanos , Tetralogia de Fallot/genéticaRESUMO
In this work, by using two kinds of viologen ligands three POM-based Compoundsâ were obtained under hydrothermal conditions, namely [AgI (bmypd)0.5 (ß-Mo8 O26 )0.5 ] (1) (bmypd â 2Cl=1,1'-[Biphenyl-4,4'-bis(methylene)]bis(4,4'-bipyridyinium)dichloride), [AgI 2 (bypy)4 (HSiW12 O40 )2 ] â 14H2 O (2) and [AgI (bypy)(γ-Mo8 O26 )0.5 ] (3) (bypyâ Cl=1-Benzyl-4,4'-bipyridyinium chloride). The structures were characterized by Fourier transform infrared spectroscopy (FT-IR), Powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS) and single crystal X-ray diffraction. Compoundsâ 1-3 show excellent photochromic ability with fast photoresponse under the irradiation of ultraviolet light with different degrees of color changes. So compoundsâ 1-3 can be used as visible ultraviolet detectors. Compoundsâ 1-3 also possess photoluminescence properties with fast and excellent fluorescence quenching effect. Compoundsâ 1-3 also can be used as inkless and erasable printing materials with suspensions of 1-3 applied to filter paper. Compoundsâ 1-3 can also produce color changes in amine vapor environment, especially in an NH3 atmosphere. Compoundsâ 1-3 can be used as organic amine detectors.
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To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia-reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p < 0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p < 0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p < 0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.
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Dexmedetomidina , Traumatismo por Reperfusão , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Camundongos , NF-kappa B/metabolismo , Oxicodona/farmacologia , Oxicodona/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , TorniquetesRESUMO
Recent advances of photonic crystals are driven to mechanical sensors and smart wearable devices; however, for chiral photonic cellulose nanocrystal (CNC) materials, vivid structural coloration and reversible mechanochromism like chameleon skin remain a big challenge. Here, we report a ternary co-assembly and post-UV-irradiation polymerization strategy to develop flexible and elastic CNC composite films, which, notably, have naked-eye-visible brilliant structural colors and stretching-induced color change covering a broad wavelength region at a moderate deformation (like skin). By adjusting the stretching, the film is designed as a smart skin to adapt to surrounding environments for camouflage. This work offers a universal strategy for constructing biomimic optically functional cellulose skins.
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Celulose , Nanopartículas , Celulose/química , Nanopartículas/química , Óptica e FotônicaRESUMO
Recent advances in structural-color cellulose nanocrystal (CNC) materials have been made toward chemical sensing applications; however, such materials lack sufficient color chroma for naked-eye observation, and their selective recognition to given chemicals as well as the corresponding mechanism has rarely been reported. Here, a dopamine-infiltration and post-polymerization approach is proposed to construct vivid structural-color composite films. The chiral nematic structure of CNC enables the structural coloration, while the strong light absorption of the polymeric co-phase, polydopamine (PDA) enhances the color chroma and visibility. By controlling the PDA amount, the composite films can detect organic solvents quantitatively and selectively via visible color changes. From the viewpoint of the compatibility and similitude principle, notably, a critical solubility parameter distance (R0) between PDA and "active" solvents is defined with a three-dimensional Hansen solubility sphere; this well constructs a rule for the sensing selectivity of the chemochromic composite films. The findings pave the foundation for the design of colorimetric sensors with specifically testing objects.
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Celulose , Nanopartículas , Celulose/química , Cor , Nanopartículas/química , Óptica e Fotônica , SolventesRESUMO
OBJECTIVE: To examine whether perioperative thermal quantitative sensory testing could be used to identify patients at high risk of chronic pain after video-assisted thoracoscopic surgery (VATS). DESIGN: A single-center, prospective, observational study. SETTING: At the Peking University People's Hospital. PARTICIPANTS: A total of 111 patients scheduled to undergo VATS were enrolled. INTERVENTIONS: Quantitative sensory testing was conducted at the anterior intercostal incision prior to surgery and after chest tube removal. MEASUREMENTS AND MAIN RESULTS: The patient's chronic pain was assessed at 3 months after surgery using a questionnaire. The incidence of chronic pain was 35 out of 107 evaluable patients (32.7%). Among the 35 patients with chronic pain, 26 had features characteristic of neuropathic pain (74.3%). Compared to the patients without chronic pain, subjects with chronic pain had a significantly greater perioperative change in cold pain threshold (CPT; p = 0.032), but not cold detection threshold, warm detection threshold, and hot pain threshold . In the multivariate regression, perioperative CPT change was associated with chronic pain after VATS (odds ratio = 1.043, p = 0.026). CONCLUSIONS: Chronic pain after VATS is typically neuropathic. The change in perioperative CPT at the incision site may help to identify patients at higher risk of chronic pain after VATS.
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Dor Crônica , Neoplasias Pulmonares , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Humanos , Neoplasias Pulmonares/cirurgia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversosRESUMO
Extracellular matrix (ECM) stiffness is closely related to the physiological and pathological states of breast tissue. The current study was aimed to investigate the effect of silk fibroin/collagen composite hydrogels with adjustable matrix stiffness on the growth and phenotype of normal breast epithelial cells. In this study, the enzymatic reaction of horseradish peroxidase (HRP) with hydrogen peroxide (H2O2) was used to change the degree of cross-linking of the silk fibroin solution. The rotational rheometer was used to characterize the composite hydrogel's biomechanical properties. Human normal mammary epithelial cell line MCF-10A were inoculated into composite hydrogels with various stiffness (19.10-4 932.36 Pa) to construct a three dimensional (3D) culture system of mammary epithelial cells. The CCK-8 assay was applied to detect the cell proliferation rate and active states in each group. Hematoxylin-Eosin (HE) staining and whole-mount magenta staining were used for histological evaluation of cell morphology and distribution. The results showed that with the increase of matrix stiffness, MCF-10A cells exhibited inhibited proliferation rate, decreased formation of acinus structures and increased branching structures. Meanwhile, with the increase of matrix stiffness, the polarity of MCF-10A cells was impeded. And the increase of matrix stiffness up-regulated the expression levels of mmp-2, mmp-3, and mmp-9 in MCF-10A cells. Among the genes related to epithelial-mesenchymal transition (EMT), the expression level of the epithelial marker gene E-cadherin was significantly down-regulated, while the interstitial cell marker gene Vimentin was up-regulated, and the expression levels of Snail, Wnt5b and Integrin ß1 in the Wnt pathway were up-regulated. These results suggest that the silk fibroin/collagen composite hydrogels with adjustable matrix stiffness regulates the proliferation and the phenotype of MCF-10A cells. The effects of increased matrix stiffness may be closely related to the changes of the polar structures and function of MCF-10A cells, as well as the occurrence of ECM-remodeling and EMT.
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Fibroínas , Colágeno/metabolismo , Células Epiteliais/metabolismo , Fibroínas/química , Fibroínas/metabolismo , Fibroínas/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/metabolismo , Peróxido de Hidrogênio , FenótipoRESUMO
CONTEXT: Paclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain. OBJECTIVE: To investigate the role of necroptosis and related changes in PTX-induced cognitive impairment. MATERIALS AND METHODS: C57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed. RESULTS: PTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-ß (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-ß (0.56-fold), and improved cognitive impairment. CONCLUSION: We established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.
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Disfunção Cognitiva , Microglia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Hipocampo , Camundongos , Necroptose , Plasticidade Neuronal , Paclitaxel/toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Salvianolic acid B(Sal B), tanshinone â ¡_A(TSN â ¡_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN â ¡_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN â ¡_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN â ¡_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN â ¡_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN â ¡_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.
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Abietanos , Acetaminofen , Antipiréticos , Benzofuranos , Doença Hepática Induzida por Substâncias e Drogas , Depsídeos , Ácido Glicirretínico , Abietanos/uso terapêutico , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Alanina Transaminase/metabolismo , Animais , Antipiréticos/efeitos adversos , Antipiréticos/uso terapêutico , Aspartato Aminotransferases/metabolismo , Benzofuranos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Depsídeos/uso terapêutico , Emulsões , Ácido Glicirretínico/uso terapêutico , Fígado/efeitos dos fármacos , Malondialdeído , CamundongosRESUMO
The optimal prescription of tanshinone â ¡_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.
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Acne Vulgar , Ácido Glicirretínico , Nanopartículas , Abietanos , Acne Vulgar/tratamento farmacológico , Animais , Portadores de Fármacos , Lipossomos , Camundongos , Tamanho da Partícula , TestosteronaRESUMO
To construct polyoxometalate-based complexes as electrode materials for supercapacitors and electrochemical sensors, we intentionally used in situ ligand transformation during the reaction. Two complexes based on polyoxometalates capped by zinc ions, H{Zn4(DIBA)4[(DIBA)(HPO2)]2(α-PMoVI8MoV4O40Zn2)} (1) and [ε-PMoV8MoVI4O37(OH)3Zn4(HDBIBA)2]·6H2O (2) [DIBA = 3,5-di(1H-imidazol-1-yl)benzoic acid, and DBIBA = 3,5-bis(1H-benzoimidazol-1-yl)benzoic acid], have been prepared successfully. The DIBA and DBIBA ligands were generated in situ from initial materials 3,5-di(1H-imidazol-1-yl)benzonitrile and 3,5-di(1H-benzoimidazol-1-yl)benzonitrile. The three-dimensional structure of 1 consisted of two-dimensional interpenetrating layers and polyoxometalate-based chains composed of bicapped α-PMo12Zn2 polyoxoanions and phosphite-modified DIBA ligands. In 2, a kind of tetracapped ε-PMo12Zn4 polyoxoanion exists, which was further linked by DBIBA ligands into a one-dimensional chain. Two complexes could be employed as not only electrode materials for supercapacitors with specific capacitances of 171.17 F g-1 for 1 and 146.77 F g-1 for 2 at 0.5 A g-1 but also efficient electrochemical sensors for detecting Cr(VI) with excellent limits of detection of 0.026 µM for 1 and 0.035 µM for 2, which represents a hopeful approach for exploiting polyoxometalate-based complexes as supercapacitor and electrochemical sensor materials.