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1.
Nat Commun ; 15(1): 2987, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582870

RESUMO

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.


Assuntos
Infecções por Henipavirus , Vírus Nipah , Humanos , Anticorpos Neutralizantes/metabolismo , Vírus Nipah/metabolismo , Anticorpos Antivirais
2.
Int J Biol Macromol ; : 131502, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38626834

RESUMO

Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected. Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found. The formation of metabolites was dependent on NADPH. Inhibition and recombinant CYP450 enzyme incubation experiments showed that CYP3A4 was the primary enzyme responsible for the metabolic activation of PLG. This study characterized the O-dealkylated metabolite (M1) through chemical synthesis. The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.

3.
J Environ Sci (China) ; 142: 21-32, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527886

RESUMO

In the context of carbon capture, utilization, and storage, the high-value utilization of carbon storage presents a significant challenge. To address this challenge, this study employed the bipolar membrane electrodialysis integrated with carbon utilization technology to prepare Na2CO3 products using simulated seawater concentrate, achieving simultaneous saline wastewater utilization, carbon storage and high-value production of Na2CO3. The effects of various factors, including concentration of simulated seawater concentrate, current density, CO2 aeration rate, and circulating flow rate of alkali chamber, on the quality of Na2CO3 product, carbon sequestration rate, and energy consumption were investigated. Under the optimal condition, the CO32- concentration in the alkaline chamber reached a maximum of 0.817 mol/L with 98 mol% purity. The resulting carbon fixation rate was 70.50%, with energy consumption for carbon sequestration and product production of 5.7 kWhr/m3 CO2 and 1237.8 kWhr/ton Na2CO3, respectively. This coupling design provides a triple-win outcome promoting waste reduction and efficient utilization of resources.


Assuntos
Dióxido de Carbono , Carbono , Carbonatos , Água do Mar , Sódio
4.
J Agric Food Chem ; 72(13): 7187-7202, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38515289

RESUMO

To determine the protective mechanism of puerarin against nonalcoholic steatohepatitis (NASH), the pharmacodynamic effects of puerarin on NASH were evaluated by using zebrafish, cells, and mice. Western blotting, flow cytometry, immunofluorescence, and qRT-PCR were used to detect the effects of puerarin on RAW264.7 autophagy and polarization. Key target interactions between autophagy and polarization were detected using immunoprecipitation. Puerarin regulated the M1/M2 ratio of RAW 264.7 cells induced by LPS + INF-γ. Transcriptomics revealed that PAI-1 is a key target of puerarin in regulating macrophage polarization. PAI-1 knockout reduced the number of M1-type macrophages and increased the number of M2-type macrophages. Puerarin regulated PAI-1 and was associated with macrophage autophagy. It increased p-ULK1 expression in macrophages and activated autophagic flux, reducing the level of PAI-1 expression. Stat3/Hif-1α and PI3K/AKT signaling pathways regulated the number of macrophage polarization phenotypes, reducing liver lipid droplet formation, alleviating liver structural abnormalities, decreasing the number of cytoplasmic vacuoles, and decreasing the area of blue collagen in NASH mice. Puerarin is a promising dietary component for NASH alleviation.


Assuntos
Isoflavonas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidor 1 de Ativador de Plasminogênio , Peixe-Zebra , Macrófagos , Autofagia , Ativação de Macrófagos
5.
Anal Chim Acta ; 1297: 342373, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38438242

RESUMO

In this work, a colorimetric and fluorescent dual-mode probe controlled by NH2-MIL-88 B (Fe, Ni) nanozymes was developed to visually detect tetracycline antibiotics (TCs) residues quantitatively, as well as accurately distinguish the four most widely used tetracycline analogs (tetracycline (TC), chrycline (CTC), oxytetracycline (OTC), and doxycycline (DC)). Colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) may be oxidized to blue oxidized TMB by the Fe Fenton reaction, which was catalyzed by the NH2-MIL-88 B (Fe, Ni) nanozyme with POD-like activity. The colorimetric detection system allows TCs to interact with NH2-MIL-88 B (Fe, Ni). This inhibits the production of ·OH, weakens the oxidation process of TMB, and ultimately lightens the blue color in the system by blocking the electron transfer between NH2-MIL-88 B (Fe, Ni) and H2O2. Furthermore, TCs can interact with NH2-MIL-88 B (Fe, Ni) as a result of the internal filtering effect, which causes the fluorescence intensity to decrease as TCs concentration increases. Additionally, a portable instrument that combines a smartphone sensing platform with colorimetric and fluorescent signals was created for the quick, visual quantitative detection of TCs. The colorimetric and fluorescent dual-mode nano platform enables color change, with detection limits (LODs) of 0.182 µM and 0.0668 µM for the spectrometer and smartphone sensor, respectively, based on the inhibition of fluorescence and enzyme-like activities by TCs. Overall, the colorimetric and fluorescence dual-mode sensor has good stability, high specificity, and an efficient way to eliminate false-positive issues associated with a single detection mode.


Assuntos
Benzidinas , Aprendizado Profundo , Compostos Heterocíclicos , Colorimetria , Peróxido de Hidrogênio , Smartphone , Tetraciclina , Antibacterianos , Corantes Fluorescentes
6.
Mol Immunol ; 167: 16-24, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310669

RESUMO

Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.


Assuntos
Asma , Interleucina-13 , Animais , Camundongos , Anti-Inflamatórios/metabolismo , Asma/induzido quimicamente , Asma/genética , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/patologia , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Interleucina-5 , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina/metabolismo , Transdução de Sinais , Células Th2 , Fatores de Transcrição/metabolismo , Sistema de Sinalização das MAP Quinases
7.
J Colloid Interface Sci ; 662: 962-975, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382379

RESUMO

This study involved the preparation of Metal Organic Frameworks (MOF)-derived Co8FeS8@Co1-xS nanoenzymes with strong interfacial interactions. The nanoenzymes presented the peroxidase (POD)-like activity and the oxidation activity of reduced glutathione (GSH). Accordingly, the dual activities of Co8FeS8@Co1-xS provided a self-cascading platform for producing significant amounts of hydroxyl radical (•OH) and depleting reduced glutathione, thereby inducing tumor cell apoptosis and ferroptosis. More importantly, the Co8FeS8@Co1-xS inhibited the anti-apoptosis protein B-cell lymphoma-2 (Bcl-2) and activated caspase family proteins, which caused tumor cell apoptosis. Simultaneously, Co8FeS8@Co1-xS affected the iron metabolism-related genes such as Heme oxygenase-1 (Hmox-1), amplifying the Fenton response and promoting apoptosis and ferroptosis. Therefore, the nanoenzyme synergistically killed anti-apoptotic tumor cells carrying Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Furthermore, Co8FeS8@Co1-xS demonstrated good biocompatibility, which paved the way for constructing a synergistic catalytic nanoplatform for an efficient tumor treatment.


Assuntos
Ferroptose , Neoplasias , Humanos , Apoptose , Neoplasias/tratamento farmacológico , Antioxidantes , Glutationa/metabolismo , Linhagem Celular Tumoral , Peróxido de Hidrogênio
8.
Food Chem ; 444: 138656, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38325090

RESUMO

Environmental pollution caused by ciprofloxacin is a major problem of global public health. A machine learning-assisted portable smartphone-based visualized molecularly imprinted electrochemiluminescence (MIECL) sensor was developed for the highly selective and sensitive detection of ciprofloxacin (CFX) in food. To boost the efficiency of electrochemiluminescence (ECL), oxygen vacancies (OVs) enrichment was introduced into the flower-like Tb@Lu2O3 nanoemitter. With the specific recognition reaction between MIP as capture probes and CFX as detection target, the ECL signal significantly decreased. According to, CFX analysis was determined by traditional ECL analyzer detector in the concentration range from 5 × 10-4 to 5 × 102 µmol L-1 with the detection limit (LOD) of 0.095 nmol L-1 (S/N = 3). Analysis of luminescence images using fast electrochemiluminescence judgment network (FEJ-Net) models, achieving portable and intelligent quick analysis of CFX. The proposed MIECL sensor was used for CFX analysis in real meat samples and satisfactory results, as well as efficient selectivity and good stability.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Impressão Molecular/métodos , Medições Luminescentes/métodos , Fotometria , Luminescência , Limite de Detecção , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
9.
Small ; : e2310769, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263803

RESUMO

Inspired by natural swarms, various methods are developed to create artificial magnetic microrobotic collectives. However, these magnetic collectives typically receive identical control inputs from a common external magnetic field, limiting their ability to operate independently. And they often rely on interfaces or boundaries for controlled movement, posing challenges for independent, three-dimensional(3D) navigation of multiple magnetic collectives. To address this challenge, self-assembled microrobotic collectives are proposed that can be selectively actuated in a combination of external magnetic and optical fields. By harnessing both actuation methods, the constraints of single actuation approaches are overcome. The magnetic field excites the self-assembly of colloids and maintains the self-assembled microrobotic collectives without disassembly, while the optical field drives selected microrobotic collectives to perform different tasks. The proposed magnetic-photo microrobotic collectives can achieve independent position and path control in the two-dimensional (2D) plane and 3D space. With this selective control strategy, the microrobotic collectives can cooperate in convection and mixing the dye in a confined space. The results present a systematic approach for realizing selective control of multiple microrobotic collectives, which can address multitasking requirements in complex environments.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38236508

RESUMO

During the development of hepatocellular carcinoma (HCC), hepatic stellate cells undergo activation and transform into cancer-associated fibroblasts (CAFs) due to the influence of tumor cells. The interaction between CAFs and tumor cells can compromise the effectiveness of chemotherapy drugs and promote tumor proliferation, invasion, and metastasis. This study explores the potential of glycyrrhetinic acid (GA)-modified liposomes (lip-GA) as a strategy for co-delivery of berberine (Ber) and doxorubicin (Dox) to treat HCC. The characterizations of liposomes, including particle size, zeta potential, polydispersity index, stability and in vitro drug release, were investigated. The study evaluated the anti-proliferation and anti-migration effects of Dox&Ber@lip-GA on the Huh-7 + LX-2 cell model were through MTT and wound-healing assays. Additionally, the in vivo drug distribution and anti-tumor efficacy were investigated using the H22 + NIH-3T3-bearing mouse model. The results indicated that Dox&Ber@lip-GA exhibited a nanoscale particle size, accumulated specifically in the tumor region, and was efficiently taken up by tumor cells. Compared to other groups, Dox&Ber@lip-GA demonstrated higher cytotoxicity and lower migration rates. Additionally, it significantly reduced the deposition of extracellular matrix (ECM) and inhibited tumor angiogenesis, thereby suppressing tumor growth. In conclusion, Dox&Ber@lip-GA exhibited superior anti-tumor effects both in vitro and in vivo, highlighting its potential as an effective therapeutic strategy for combating HCC.

11.
Mikrochim Acta ; 191(1): 79, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183441

RESUMO

Antibiotic residues in the environment pose a serious threat to ecosystems and human health. Therefore, it is important to develop sensitive and rapid in situ detection methods. In this work, the designed nanozymes, with excellent four enzyme activities, were proved to be constituted of unique hollow nanocage structures (CoZnSe@CN HCs). Based on the peroxidase-like enzymes, a portable colorimetric sensor was constructed for the on-site determination of tetracycline (TC) in real samples. The linear range of TC detection was 0.1-100 µM, and the detection limit was 0.02 µM. At the same time, colorimetric detection and smartphones have also been combined for on-site colorimetric detection of TC. In-depth exploration of the detection mechanism showed that TC could be bound with the material, inhibiting the production of oxidized 3,3',5,5'-tetramethylbenzidine. The sensor was also used for the detection of TC in environmental soil and water samples. This study can provide an intelligent detection method for environmental monitoring.


Assuntos
Ecossistema , Realidade Virtual , Humanos , Smartphone , Tetraciclina , Antibacterianos
12.
J Hazard Mater ; 465: 133156, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38061128

RESUMO

Ethephon (ETH) is a common pesticide, and its overuse has resulted in a variety of health problems for humans. However, the existing ETH detection methods are tedious and time-consuming, and real-time ETH identification remains a significant difficulty. To mitigate this concern, a dual-emission ratiometric fluorescent probe Ru@ZrMOF was rationally synthesized for the detection of ETH. In the presence of ETH, the emission peak at 435 nm gradually increased, while the peak at 600 nm remained constant, accompanied by the fluorescence color change from red, pink, blue-violet to blue. The fluorescence intensity ratio (F435/F600) demonstrated two linear relations with the ETH concentration ranges at 3 - 50 µM and 50 - 500 µM, with a lowest detection limit at 1 µM. This was attributed to the formation of Zr-O-P bonds which attenuated the ligand-metal charge transfer (LMCT) process, resulting in the recovery of blue fluorescence of the ligand 2-Aminoterephthalic acid (2-APDC). To validate the practical application of the developed platform, a YOLO v5x-based WeChat applet "96 Speckles" was developed, and a 96-well plate and smartphone-embedded 3D-printed portable toolbox was designed for the real-time intelligent detection of ETH. This smart platform allows for real-time and efficient ETH analysis in various real samples including apples, pears and tomatoes.

13.
Br J Nutr ; 131(3): 369-383, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-37694489

RESUMO

Feeding whole prey to felids has shown to benefit their gastrointestinal health. Whether this effect is caused by the chemical or physical nature of whole prey is unknown. Fifteen domestic cats, as a model for strict carnivores, were either fed minced mice (MM) or whole mice (WM), to determine the effect of food structure on digestibility, mean urinary excretion time (MUET) of 15N, intestinal microbial activity and fermentation products. Faeces samples were collected after feeding all cats a commercially available extruded diet (EXT) for 10 d before feeding for 19 d the MM and WM diets with faeces and urine collected from day 11 to 15. Samples for microbiota composition and determination of MUET were obtained from day 16 to 19. The physical structure of the mice diet (minced or not) did not affect large intestinal fermentation as total SCFA and branched-chain fatty acid (BCFA), and most biogenic amine (BA) concentrations were not different (P > 0·10). When changing from EXT to the mice diets, the microbial community composition shifted from a carbolytic (Prevotellaceae) to proteolytic (Fusobacteriaceae) profile and led to a reduced faecal acetic to propionic acid ratio, SCFA, total BCFA (P < 0·001), NH3 (P = 0·04), total BA (P < 0·001) and para-cresol (P = 0·08). The results of this study indicate that food structure within a whole-prey diet is less important than the overall diet type, with major shifts in microbiome and decrease in potentially harmful fermentation products when diet changes from extruded to mice. This urges for careful consideration of the consequences of prey-based diets for gut health in cats.


Assuntos
Ração Animal , Dieta , Gatos , Animais , Camundongos , Ração Animal/análise , Dieta/veterinária , Fezes/química , Trato Gastrointestinal , Ácidos Graxos/análise , Fermentação , Fenômenos Fisiológicos da Nutrição Animal , Digestão
14.
Cell Biochem Funct ; 42(1): e3899, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38088534

RESUMO

Asthma is a common respiratory disease associated with airway inflammation. Nerolidol is an acyclic sesquiterpenoid with anti-inflammatory properties. BALB/C mice were sensitized with ovalbumin (OVA) to induce asthma symptoms and given different doses of Nerolidol. We found that Nerolidol reduced OVA-induced inflammatory cell infiltration, the number of goblet cells and collagen deposition in lung tissue. Nerolidol reduced the OVA-specific IgE levels in serum and alveolar lavage fluid in an asthma model. Immunohistochemical staining of α-SMA (the marker of airway smooth muscle) showed that Nerolidol caused bronchial basement membrane thinning in asthmatic mice. The hyperplasia of airway smooth muscle cells (ASMCs) is an important feature of airway remodeling in asthma. ASMCs were treated with 10 ng/mL TGF-ß to simulate the pathological environment of asthma in vitro and then treated with different doses of Nerolidol. Nerolidol inhibited the activity of TGF-ß/Smad signaling pathway both in the lung tissue of OVA-induced mouse and TGF-ß-stimulated ASMCs. 16s rRNA sequencing was performed on feces of normal mice, the changes of intestinal flora in OVA-induced asthmatic mice and Nerolidol-treated asthmatic mice were studied. The results showed that Nerolidol reversed the reduced gut microbial alpha diversity in asthmatic mice. Nerolidol changed the relative abundance of gut bacteria at different taxonomic levels. At the phylum level, the dominant bacteria were Bacteroidota, Firmicutes, and Proteobacteria. At the genus level, the dominant bacteria were Lactobacillus, Muribaculaceae, Bacteroides, and Lachnospiraceae. We conclude that Nerolidol attenuates OVA-induced airway inflammation and alters gut microbes in mice with asthma via TGF-ß/Smad signaling.


Assuntos
Asma , Microbioma Gastrointestinal , Sesquiterpenos , Animais , Camundongos , Ovalbumina/efeitos adversos , Ovalbumina/metabolismo , Remodelação das Vias Aéreas , RNA Ribossômico 16S/metabolismo , Camundongos Endogâmicos BALB C , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Sesquiterpenos/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Líquido da Lavagem Broncoalveolar/química , Fator de Crescimento Transformador beta/metabolismo , Modelos Animais de Doenças
15.
Biosens Bioelectron ; 248: 115941, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38160634

RESUMO

Environmental pollution caused by tetracycline antibiotics is a major concern of global public health. Here, a novel and portable molecularly imprinted electrochemiluminescence (MIECL) sensor based on smartphones for highly sensitive detection of chlortetracycline (CTC) has been successfully established. The high-performance ECL emitter of biomass carbon (BC) encapsulated CdZnTeS (CdZnTeS@BC) was successfully synthesized by hydrothermal. The enhanced ECL performance was ascribed to the introduction of the BC and increased the overall electrical conductivity of the nanoemitter, as well as increased the number of sulfur vacancies and doping on the surface of the emitter based on density functional theory calculations. An aniline-CTC molecular imprinted polymer was synthesized on the surface of the CdZnTeS@BC modified electrode by in-situ electropolymerization. The decrease in MIECL signal was attributed to the increase in impedance effect. The MIECL nanoplatform enabled a wide linear relationship in the range of 0.05-100 µmol/L with a detection limit of 0.029 µmol/L for spectrometer sensors. Interestingly, the light emitted during the MIECL reaction can be captured by a smartphone. Thus, machine learning was used to screen the photos that were taken, and color analysis was carried out on the screened photos by self-developed software, thus achieving a portable, convenient, and intelligent sensing mode. Finally, the sensor obtains satisfactory results in the detection of actual samples, with no significant differences from those of liquid chromatography.


Assuntos
Técnicas Biossensoriais , Cádmio , Clortetraciclina , Impressão Molecular , Telúrio , Zinco , Carbono/química , Medições Luminescentes/métodos , Impressão Molecular/métodos , Inteligência Artificial , Biomassa , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção
16.
Small ; : e2309593, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126566

RESUMO

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2 @MoS2 ) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2 @MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 - ) to hydrogen peroxide (H2 O2 ), and then the resulting H2 O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2 @MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2 O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2 @MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.

17.
Int J Mol Sci ; 24(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37958545

RESUMO

Drug-induced liver injury (DILI) is a widespread and harmful disease, and is closely linked to acute endoplasmic reticulum (ER) stress. Previous reports have shown that acute ER stress can suppress hepatic gluconeogenesis and even leads to hypoglycemia. However, the mechanism is still unclear. MAPK phosphatase 3 (MKP-3) is a positive regulator for gluconeogenesis. Thus, this study was conducted to investigate the role of MKP-3 in the suppression of gluconeogenesis by acute ER stress, as well as the regulatory role of acute ER stress on the expression of MKP-3. Results showed that acute ER stress induced by tunicamycin significantly suppressed gluconeogenesis in both hepatocytes and mouse liver, reduced glucose production level in hepatocytes, and decreased fasting blood glucose level in mice. Additionally, the protein level of MKP-3 was reduced by acute ER stress in both hepatocytes and mouse liver. Mkp-3 deficiency eliminated the inhibitory effect of acute ER stress on gluconeogenesis in hepatocytes. Moreover, the reduction effect of acute ER stress on blood glucose level and hepatic glucose 6-phosphatase (G6pc) expression was not observed in the liver-specific Mkp-3 knockout mice. Furthermore, activation of protein kinase R-like ER kinase (PERK) decreased the MKP-3 protein level, while inactivation of PERK abolished the reduction effect of acute ER stress on the MKP-3 protein level in hepatocytes. Taken together, our study suggested that acute ER stress could suppress hepatic gluconeogenesis by stimulating MKP-3 degradation via PERK, at least partially. Thus, MKP-3 might be a therapeutic target for DILI-related hypoglycemia.


Assuntos
Fosfatase 6 de Especificidade Dupla , Gluconeogênese , Hipoglicemia , Animais , Camundongos , Glicemia/metabolismo , Estresse do Retículo Endoplasmático , Hepatócitos/metabolismo , Hipoglicemia/metabolismo , Fígado/metabolismo , Camundongos Knockout , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Fosfatase 6 de Especificidade Dupla/metabolismo
18.
Sci Adv ; 9(45): eadj4201, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37948530

RESUMO

Active matter systems feature a series of unique behaviors, including the emergence of collective self-assembly structures and collective migration. However, realizing collective entities formed by synthetic active matter in spaces without wall-bounded support makes it challenging to perform three-dimensional (3D) locomotion without dispersion. Inspired by the migration mechanism of plankton, we propose a bimodal actuation strategy in the artificial colloidal systems, i.e., combining magnetic and optical fields. The magnetic field triggers the self-assembly of magnetic colloidal particles to form a colloidal collective, maintaining numerous colloids as a dynamically stable entity. The optical field allows the colloidal collectives to generate convective flow through the photothermal effect, enabling them to use fluidic currents for 3D drifting. The collectives can perform 3D locomotion underwater, transit between the water-air interface, and have a controlled motion on the water surface. Our study provides insights into designing smart devices and materials, offering strategies for developing synthetic active matter capable of controllable collective movement in 3D space.

19.
ACS Appl Mater Interfaces ; 15(47): 54466-54477, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37971298

RESUMO

In this work, CuO/Fe2O3 nanozymes with high peroxidase-like activity were synthesized by using hydrothermal and calcination methods. The high-resolution transmission electron microscopy (HRTEM) proved that the heterogeneous interface of CuO/Fe2O3 was the main reason for the high enzyme-like activity. Strong interactions of CuO and Fe2O3 were successfully verified by X-ray absorption near-edge structure (XANES) characterization. Experiments and density functional theory (DFT) calculations were also used to explain the increased enzyme activity. The heterogeneous interface acted as the main active center, facilitating the electron transfer from CuO to Fe2O3. A colorimetric and intelligent sensing system was constructed based on deep learning. Using the peroxidase-like activity of CuO/Fe2O3, a platform for glufosinate pesticides and chlortetracycline hydrochloride (CTC) with the signal "on-off-on" changes were established. The limit of detection (LOD) of glufosinate and CTC was 28 and 0.69 µM, respectively. It was successfully applied in the detection of environmental water and soil. This study can provide an intelligent detection method for environmental monitoring.


Assuntos
Clortetraciclina , Peroxidases/química , Peroxidase , Antioxidantes
20.
ACS Appl Mater Interfaces ; 15(41): 48506-48518, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37796018

RESUMO

In this study, we designed and fabricated a spermine-responsive triple-emission ratiometric fluorescent probe using dual-emissive carbon nanoparticles and quantum dots, which improve the sensor's accuracy and reduce interfering environmental effects. The probe is advantageous for the proportionate detection of spermine because it has good emission resolution, and the maximum points of the two emission peaks differ by 95 nm. As a proof of concept, cuvettes and a 96-well plate were combined with a smartphone and YOLO series algorithms to accomplish real-time, visual, and high-throughput detection of seafood and meat freshness. In addition, the reaction mechanism was verified by density functional theory and fundamental characterizations. Upon exposure to different amounts of spermine, the intensity of the fluorescent probe changed linearly, and the fluorescent color shifted from yellow-green to red, with a limit of detection of 0.33 µM. To enable visual identification of food-originated spermine, a hydrogel-based visual sensing platform was successfully developed utilizing the triple-emission fluorescent probe. Consequently, spermine could be identified and quantified without complicated equipment.


Assuntos
Pontos Quânticos , Espermina , Corantes Fluorescentes , Carbono , Limite de Detecção
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