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1.
Mol Biol Rep ; 51(1): 533, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642169

RESUMO

BACKGROUND: Sepsis may be linked to oxidative stress and can be controlled by itaconate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nevertheless, the itaconate impact on sepsis-associated acute kidney injury (SA-AKI) has yet to be definitively established. METHODS: We employed SA-AKI mouse model through a cecal ligation and puncture (CLP) procedure for the in vivo investigation of the potential nephroprotective effect of itaconate in this study. A plasmid was transfected into RAW264.7 cells to examine the Nrf2 pathway function after itaconate administration. Finally, the immune-responsive gene 1-knockout (IRG1-/-) mice were used to study the itaconate impacts on oxidative stress-induced SA-AKI. RESULTS: We have shown that 4-octyl itaconate (OI) significantly reduced CD11b-positive macrophage aggregation and activated the Nrf2 pathway in the bone marrow-derived macrophages (BMDM). The impacts of Nrf2 inhibitor ML385 on the anti-inflammatory and antioxidant properties of itaconate were found to be partial. OI inhibited lipopolysaccharide-induced oxidative stress injury in RAW264.7 macrophages and activated Nrf2 in the nucleus to hinder the expression of nuclear factor kappa B p65, thereby suppressing oxidative stress injury in the macrophages. Additionally, the introduction of the transfected plasmid resulted in a partial inhibition of the anti-inflammatory impact of itaconate. The kidney injury caused by sepsis exhibited greater severity in the IRG1-/- mice than in the wild type mice. Exogenous OI partially attenuated the kidney injury induced by sepsis in the IRG1-/- mice and suppressed the oxidative stress injury in macrophages. CONCLUSIONS: This investigation offers new proof to support the itaconate function in the development and progression of SA-AKI and shows a new possible therapeutic agent for the SA-AKI treatment.


Assuntos
Injúria Renal Aguda , Sepse , Succinatos , Camundongos , Animais , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ativação de Macrófagos , Estresse Oxidativo , Injúria Renal Aguda/etiologia , Anti-Inflamatórios/farmacologia , Sepse/complicações
2.
Nat Rev Drug Discov ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565913

RESUMO

Prodrugs are derivatives with superior properties compared with the parent active pharmaceutical ingredient (API), which undergo biotransformation after administration to generate the API in situ. Although sharing this general characteristic, prodrugs encompass a wide range of different chemical structures, therapeutic indications and properties. Here we provide the first holistic analysis of the current landscape of approved prodrugs using cheminformatics and data science approaches to reveal trends in prodrug development. We highlight rationales that underlie prodrug design, their indications, mechanisms of API release, the chemistry of promoieties added to APIs to form prodrugs and the market impact of prodrugs. On the basis of this analysis, we discuss strengths and limitations of current prodrug approaches and suggest areas for future development.

4.
Biochem Pharmacol ; : 116217, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641306

RESUMO

The Hippo pathway is a key regulator of tissue growth, organ size, and tumorigenesis. Activating the Hippo pathway by gene editing or pharmaceutical intervention has been proven to be a new therapeutic strategy for treatment of the Hippo pathway-dependent cancers. To now, a number of compounds that directly target the downstream effector proteins of Hippo pathway, including YAP and TEADs, have been disclosed, but very few Hippo pathway activators are reported. Here, we discovered a new class of Hippo pathway activator, YL-602, which inhibited CTGF expression in cells irrespective of cell density and the presence of serum. Mechanistically, YL-602 activates the Hippo pathway via MST1/2, which is different from known activators of Hippo pathway. In vitro, YL-602 significantly induced tumor cell apoptosis and inhibited colony formation of tumor cells. In vivo, oral administration of YL-602 substantially suppressed the growth of cancer cells by activation of Hippo pathway. Overall, YL-602 could be a promising lead compound, and deserves further investigation for its mechanism of action and therapeutic applications.

5.
Apoptosis ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641760

RESUMO

To investigate the protective role of immune response gene 1 (IRG1) and exogenous itaconate in autoimmune hepatitis (AIH) and elucidate the underlying mechanisms. Wild-type and IRG1-/- AIH mouse models were established, and samples of liver tissue and ocular blood were collected from each group of mice to assess the effects of IRG1/itaconate on the expression of pro- and anti-inflammatory cytokines. The levels of liver enzymes and related inflammatory factors were determined using enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR). Liver histomorphology was detected through hematoxylin and eosin staining and then scored for liver injury, and the infiltration levels of tissue-resident memory T (TRM) cells and related molecules in the liver tissue were detected through immunofluorescence staining in vitro. RNA sequencing and gene enrichment analysis were conducted to identify the corresponding molecules and pathways, and lentiviral transfection was used to generate TRM cell lines with IRG1, Jak3, Stat3, and p53 knockdown. Real-time quantitative PCR and western blot were performed to detect the expression levels of relevant mRNAs and proteins in the liver tissue and cells. The percentage of apoptotic cells was determined using flow cytometry. IRG1/itaconate effectively reduced the release of pro-inflammatory cytokines and the pathological damage to liver tissue, thereby maintaining normal liver function. At the same time, IRG1/itaconate inhibited the JAK3/STAT3 signaling pathway, regulated the expression of related downstream proteins, and inhibited the proliferation and promoted the apoptosis of CD69+CD103+CD8+ TRM cells. For the first time, P53 was found to act as a downstream molecule of the JAK3/STAT3 pathway and was regulated by IRG1/itaconate to promote the apoptosis of CD8+ TRM cells. IRG1/itaconate can alleviate concanavalin A-induced autoimmune hepatitis in mice by inhibiting the proliferation and promoting the apoptosis of CD69+CD103+CD8+ TRM cells via the JAK3/STAT3/P53 pathway.

6.
Environ Sci Pollut Res Int ; 31(16): 24412-24424, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38441738

RESUMO

The crux of groundwater protection lies in a profound understanding of the sources of pollutants and their impacts on human health. This study selected 47 groundwater samples from the Fengshui mining area in central Shandong Province, China, employing advanced hydrogeochemical techniques, positive matrix factorization (PMF), and Monte Carlo analysis methods, aimed at unveiling the characteristics, origins, and health risks of water pollutants. The results indicated that the majority of samples exhibited a slightly alkaline nature. Notably, the concentrations of fluoride (F-) and nitrate (NO3-) exceeded China's safety standards in 40.43% and 23.40% of the samples, respectively. Moreover, a water quality index (WQI) below 50 was observed in approximately 68.09% of the sites, suggesting that the water quality in these areas generally met acceptable levels. However, regions with higher WQI values were predominantly located in the northern and southern parts of the mining area. PMF analysis revealed that regional geological and industrial activities were the primary factors affecting water quality, followed by mining discharges, fundamental geological and agricultural processes, and leachate enrichment activities. The health risk assessment highlighted the heightened sensitivity of the youth demographic to fluoride, with a more pronounced non-carcinogenic risk compared to nitrate, affecting about 31.89% of the youth population. Hence, it is imperative for local authorities and relevant departments to take prompt actions to remediate groundwater contamination to minimize public health risks.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Adolescente , Humanos , Monitoramento Ambiental/métodos , Nitratos/análise , Fluoretos/análise , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Qualidade da Água , Compostos Orgânicos , Medição de Risco , China
7.
BMC Surg ; 24(1): 92, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504206

RESUMO

BACKGROUND: To investigate the role of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) as early predictors of infectious complications after laparoscopic gastric cancer surgery. METHODS: Patients who underwent laparoscopic gastric cancer surgery between January 2020 and June 2022 were retrospectively enrolled. IL-6, PCT, and CRP levels were assessed before surgery and on postoperative days (PODs) 3 and 5. Differences in serum IL-6, PCT, and CRP levels between the infected and non-infected groups were compared. The diagnostic accuracy was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 206 patients were enrolled, and 21 patients (10.19%) developed postoperative infections. Serum IL-6, PCT, and CRP levels in the infected group were significantly higher than those in the non-infected group on PODs 3 and 5. IL-6 with an optimal cutoff value of 84.00 pg/mL (AUC 0.84), PCT with an optimal cutoff value of 1.39 ng/mL (AUC 0.80), CRP with an optimal cutoff value of 150.00 mg/L (AUC 0.76) on POD 3 had superior diagnostic accuracy in predicting postoperative infections. Multivariate analysis identified PCT and IL-6 levels on POD 3 as independent risk factors, the AUC of the combination of IL-6 and PCT was 0.89. The Delong test showed no difference between the AUC of IL-6 alone and IL-6 combined with PCT prediction (P = 0.07, Z = 1.81). CONCLUSIONS: IL-6 level on POD 3 is an excellent predictor of infectious complications following laparoscopic gastric cancer surgery. Patients with IL-6 levels lower than 84.00 pg/mL on POD 3 can ensure safe early discharge with a low probability of infection.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Interleucina-6 , Neoplasias Gástricas/cirurgia , Calcitonina , Estudos Retrospectivos , Pró-Calcitonina , Proteína C-Reativa/metabolismo , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Curva ROC , Laparoscopia/efeitos adversos , Biomarcadores
8.
Opt Express ; 32(4): 4778-4798, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439222

RESUMO

In single-shot speckle projection profilometry (SSPP), the projected speckle inevitably undergoes changes in shape and size due to variations such as viewing angles, complex surface modulations of the test object and different projection ratios. These variations introduce randomness and unpredictability to the speckle features, resulting in erroneous or missing feature extraction and subsequently degrading 3D reconstruction accuracy across the tested surface. This work strives to explore the relationship between speckle size variations and feature extraction, and address the issue solely from the perspective of network design by leveraging specific variations in speckle size without expanding the training set. Based on the analysis of the relationship between speckle size variations and feature extraction, we introduce the NMSCANet, enabling the extraction of multi-scale speckle features. Multi-scale spatial attention is employed to enhance the perception of complex and varying speckle features in space, allowing comprehensive feature extraction across different scales. Channel attention is also employed to selectively highlight the most important and representative feature channels in each image, which is able to enhance the detection capability of high-frequency 3D surface profiles. Especially, a real binocular 3D measurement system and its digital twin with the same calibration parameters are established. Experimental results imply that NMSCANet can also exhibit more than 8 times the point cloud reconstruction stability (Std) on the testing set, and the smallest change range in terms of Mean~dis (0.0614 mm - 0.4066 mm) and Std (0.0768 mm - 0.7367 mm) when measuring a standard sphere and plane compared to other methods, faced with the speckle size changes, meanwhile NMSCANet boosts the disparity matching accuracy (EPE) by over 35% while reducing the matching error (N-PER) by over 62%. Ablation studies and validity experiments collectively substantiate that our proposed modules and constructed network have made significant advancements in enhancing network accuracy and robustness against speckle variations.

9.
Anatol J Cardiol ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445622

RESUMO

BACKGROUND: Empagliflozin (EMPA) demonstrates cardioprotective effects on the patients with heart failure, but its effects in cardiorenal syndrome (CRS) remain unspecified. The purpose of the exploratory study was to investigate the effect of EMPA on patients with type 2 CRS and type 2 diabetes mellitus (DM). METHODS: This study was a randomized trial of patients with type 2 CRS and DM done between December 2020 and January 2022. Patients were randomly allocated to the control group and the EMPA group using EMPA as an add-on treatment. Serum interleukin 6 (IL-6), janus kinase 2 (JAK-2), and signal transducer and activator of transcription 3 (STAT-3) concentrations were measured in 102 patients with CRS and healthy individuals without any disease using enzyme-linked immunosorbent assay before and after treatment. The evaluation of renal function was measured by immunoturbidimetry, and cardiac function was estimated by doppler echocardiography. Rates of adverse events and major adverse cardiac events (MACE) were documented. RESULTS: The results showed that EMPA decreased the level of IL-6 but increased the level of JAK-2 and STAT-3 in patients. Additionally, the results suggest EMPA significantly reduced the incidence of MACE compared to the control group, while the rate of adverse events did not significantly differed. CONCLUSIONS: Our study suggested that the cardiorenal benefits conferred by EMPA might be driven by anti-inflammatory effects, cooperated with the activation of JAK2/STAT3 signaling pathways, leading to modest short-term improvements in patients with type 2 CRS. The overall safety and low complication make EMPA a significant choice for clinical application.

10.
bioRxiv ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38405797

RESUMO

With over 270 unique occurrences in the human genome, peptide-recognizing PDZ domains play a central role in modulating polarization, signaling, and trafficking pathways. Mutations in PDZ domains lead to diseases such as cancer and cystic fibrosis, making PDZ domains attractive targets for therapeutic intervention. D-peptide inhibitors offer unique advantages as therapeutics, including increased metabolic stability and low immunogenicity. Here, we introduce DexDesign, a novel OSPREY-based algorithm for computationally designing de novo D-peptide inhibitors. DexDesign leverages three novel techniques that are broadly applicable to computational protein design: the Minimum Flexible Set, K*-based Mutational Scan, and Inverse Alanine Scan, which enable exponential reductions in the size of the peptide sequence search space. We apply these techniques and DexDesign to generate novel D-peptide inhibitors of two biomedically important PDZ domain targets: CAL and MAST2. We introduce a new framework for analyzing de novo peptides-evaluation along a replication/restitution axis-and apply it to the DexDesign-generated D-peptides. Notably, the peptides we generated are predicted to bind their targets tighter than their targets' endogenous ligands, validating the peptides' potential as lead therapeutic candidates. We provide an implementation of DexDesign in the free and open source computational protein design software OSPREY.

11.
World J Diabetes ; 15(1): 105-125, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38313853

RESUMO

BACKGROUND: Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM: To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS: Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS: In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1ß induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION: This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

12.
Front Cell Dev Biol ; 12: 1327167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371923

RESUMO

Autophagy is a common biological phenomenon in eukaryotes that has evolved and reshaped to maintain cellular homeostasis. Under the pressure of starvation, hypoxia, and immune damage, autophagy provides energy and nutrients to cells, which benefits cell survival. In mammals, autophagy is an early embryonic nutrient supply system involved in early embryonic development, implantation, and pregnancy maintenance. Recent studies have found that autophagy imbalance in placental tissue plays a key role in the occurrence and development of pregnancy complications, such as gestational hypertension, gestational obesity, premature birth, miscarriage, and intrauterine growth restriction. This mini-review summarizes the molecular mechanism of autophagy regulation, the autophagy pathways, and related factors involved in placental tissue and comprehensively describes the role of autophagy in pregnancy complications.

13.
Appl Spectrosc ; : 37028241233016, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389424

RESUMO

Aminophylline (AMP) is a bronchodilator. The therapeutic and toxic doses are very close. Therefore, therapeutic drug monitoring (TDM) of AMP is essential in clinical practice. Microgels were synthesized by free radical precipitation polymerization. Silver@poly(N-isopropyl acrylamide) (Ag@PNIPAM) hybrid microgels were obtained by loading silver (Ag) nanoparticles into the three-dimensional network of the microgels by in situ reduction. The microgel is a three-dimensional reticular structure with tunable pore size, large specific surface area, and good biocompatibility, which can be used as a sorbent for solid-phase extraction (SPE) of target molecules in complex matrices and as a surface-enhanced Raman spectroscopy (SERS) substrate. We optimized the conditions affecting SERS enhancement, such as silver nitrate (AgNO3) concentration and SPE time, according to the SERS strategy of Ag@PNIPAM hybrid microgels to achieve label-free TDM for trace AMP in human serum. The results showed good linearity between the logarithmic concentration of AMP and its SERS intensity in the range of 1-1.1 × 102 µg/mL, with a correlation coefficient (R2) of 0.9947 and a low detection limit of 0.61 µg/mL. The assay accuracy was demonstrated by spiking experiments, with recoveries ranging from 93.0 to 101.8%. The method is rapid, sensitive, reproducible, requires simple sample pretreatment, and has good potential for use in clinical treatment drug monitoring.

14.
Bioresour Technol ; 397: 130475, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387845

RESUMO

To alleviate the inhibitory effects of salt and oil on food waste compost, the compost was inoculated with salt-tolerant and oil-degrading Bacillus safensis YM1. The YM1 inoculation could effectively improve compost maturation index. Compared with uninoculated group, the oil content and Cl- concentration in the 0.5% YM1-inoculated compost decreased significantly by 19.7% and 8.1%, respectively. The addition of the YM1 inoculant substantially altered the richness and composition of the microbial community during composting, as evidenced by the identification of 47 bacterial and 42 fungal biomarker taxa. The enrichment of some oil-degrading salt-tolerant microbes (Bacillus, Haloplasma, etc.) enhanced nutrient conversion, which is crucial for the improved maturity of the YM1 compost. This study demonstrated that YM1 could regulate both abiotic and biotic processes to improve high-salt and oily food waste composting, which may be an effective inoculant in the industrial-scale composting.


Assuntos
Bacillus , Compostagem , Eliminação de Resíduos , 60659 , Alimentos , Solo
15.
Anal Chim Acta ; 1292: 342255, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309848

RESUMO

BACKGROUND: ß-thalassemia is a blood disorder caused by autosomal mutations. Gene modulation therapy to activate the γ-globin gene to induce fetal hemoglobin (HbF) synthesis has become a new option for the treatment of ß-thalassemia. MicroRNA-210 (miR-210) contributes to studying the mechanism regulating γ-globin gene expression and is a potential biomarker for rapid ß-thalassemia screening. Traditional miRNA detection methods perform well but necessitate complex and time-consuming miRNA sample processing. Therefore, the development of a sensitive, accurate, and simple miRNA level monitoring method is essential. RESULTS: We have developed a non-enzymatic surface-enhanced Raman scattering (SERS) biosensor utilizing a signal cascade amplification of catalytic hairpin assembly reaction (CHA) and proximity hybridization-induced hybridization chain reaction (HCR). Au@Ag NPs were used as the SERS substrate, and methylene blue (MB)- modified DNA hairpins were used as the SERS tags. The SERS assay involved two stages: implementing the CHA-HCR cascade signal amplification strategy and conducting SERS measurements on the resulting product. The HCR was started by the products of target-triggered CHA, which formed lengthy nicked double-stranded DNA (dsDNA) on the Au@Ag NPs surface to which numerous SERS tags were attached, leading to a significant increase in the SERS signal intensity. High specificity and sensitivity for miR-210 detection was achieved by monitoring MB SERS intensity changes. The suggested SERS biosensor has a low detection limit of 5.13 fM and is capable of detecting miR-210 at concentration between 10 fM and 1.0 nM. SIGNIFICANCE: The biosensor can detect miR-210 levels in the erythrocytes of ß-thalassemia patients, enabling rapid screening for ß-thalassemia and suggesting a novel approach for investigating the regulation mechanism of miR-210 on γ-globin gene expression. In the meantime, this innovative technique has the potential to detect additional miRNAs and to become an important tool for the early diagnosis of diseases and for biomedical research.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Talassemia beta , Humanos , Talassemia beta/diagnóstico , Talassemia beta/genética , gama-Globinas , DNA , Técnicas Biossensoriais/métodos , Limite de Detecção , Análise Espectral Raman , Ouro
16.
Epidemiology ; 35(3): 408-417, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38261409

RESUMO

BACKGROUND: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems. METHODS: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects. RESULTS: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes. CONCLUSIONS: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences.


Assuntos
Convulsões , Transtornos do Sono-Vigília , Criança , Humanos , Inquéritos e Questionários , Cidades , China/epidemiologia , Transtornos do Sono-Vigília/epidemiologia
17.
Phytochemistry ; 219: 113988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224846

RESUMO

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.


Assuntos
Hedyotis , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/química , Testes de Sensibilidade Microbiana , Alcaloides Indólicos/química
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 310: 123924, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38262293

RESUMO

Determination of antiepileptic drugs and antipsychotics in human serum is significant in individualized drug administration and therapeutic drug monitoring (TDM). In this study, we developed a rapid label-free TDM method for the antiepileptic drug carbamazepine (CBZ) and the antipsychotic clozapine (CLO) in human serum. This detection strategy is based on the combination of surface-enhanced Raman scattering (SERS) and magnetic solid-phase extraction (MSPE). Initially, Fe3O4@SiO2@MIL-101(Fe) nanocomposites were synthesized by the layer-by-layer self-assembly method and characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller, ultraviolet-visible, and Fourier transform infrared analyses. Subsequently, CBZ and CLO were detected in human serum using Fe3O4@SiO2@MIL-101(Fe) as the solid-phase extraction adsorbent and Ag nanoparticles as SERS substrates. The potential of the MSPE-SERS method for the label-free TDM of CBZ and CLO was then investigated. Fe3O4@SiO2@MIL-101(Fe) prevents magnetic particle aggregation and demonstrates rapid magnetic separation capability that simplifies the pretreatment process and reduces interference from complex matrices. Its large surface area can effectively enrich targets in complex matrices, thereby improving the SERS detection sensitivity. The linearity between CBZ and CLO was excellent over the concentration range of 0.1-100 µg/mL (calculated as the intensity of the SERS characteristic peaks of CBZ and CLO at 728 cm and 1054 cm-1, respectively), with correlation coefficients (R2) of 0.9987 and 0.9957, and detection limits of 0.072 and 0.12 µg/mL, respectively. The recoveries of CBZ with CLO ranged from 94.0 % to 105.0 %, and their relative standard deviations were <6.8 %. Compared to other assays, the developed MSPE-SERS method has the advantages of simple sample pretreatment, rapid detection, and good reproducibility, which provides a novel approach for the TDM of other drugs.


Assuntos
Antipsicóticos , Clozapina , Nanopartículas Metálicas , Estruturas Metalorgânicas , Humanos , Análise Espectral Raman , Dióxido de Silício/química , Reprodutibilidade dos Testes , Monitoramento de Medicamentos , Prata , Carbamazepina , Fenômenos Magnéticos , Extração em Fase Sólida/métodos , Limite de Detecção , Cromatografia Líquida de Alta Pressão/métodos
19.
Appl Opt ; 63(2): 383-389, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227232

RESUMO

The three-dimensional (3D) measurement task of complex microstructures holds paramount significance in the domains of precision manufacturing and inspection. The calibration of the 3D system heavily determines the final reconstruction accuracy. The widely adopted system calibration method is phase-height mapping (PHM) and stereo vision (SV) based. The former can be applied directly to the calculation without considering the imaging model of the system, but it relies on highly precise and expensive translation stages or standard blocks. The latter's accuracy cannot be guaranteed because it is difficult to accurately calibrate the projector. In this paper, we establish an optically coupled microscopic fringe projection profilometry system that consists of a Scheimpflug pinhole projector and a super-low distortion bi-telecentric camera. We introduce a simplified 3D system calibration approach that combines phase modulation transfer and ray propagation. Our method enables the simultaneous calibration of the system, including the calibration of the projector, camera, and the phase to a 3D coordinates relationship, using only a 2D target. The calibrated projector's external parameters are used to obtain the target's complete poses, and then the direct mapping coefficients of the phase to the 3D coordinates can be obtained through the optical geometry structure and phase labels. Comparable experiments verify the feasibility of the proposed method.

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