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Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.
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Cardiotónicos , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas , Piridinas , Humanos , Animales , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Piridinas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/metabolismo , Relación Estructura-Actividad , Cardiotónicos/farmacología , Cardiotónicos/química , Cardiotónicos/síntesis química , Cardiotónicos/uso terapéutico , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Masculino , Imidazoles/farmacología , Imidazoles/química , Imidazoles/síntesis química , Imidazoles/uso terapéutico , Ratones Desnudos , Descubrimiento de DrogasRESUMEN
DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.
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Biochar has been used to enhance methane generation from anaerobic digestion through establishing direct interspecific electron transfer between microorganisms. However, the microbial communication is still inadequate, thereby limiting further methane production improvement contributed by biochar. This study investigated the roles of quorum-sensing molecules, acylated homoserine lactone (AHL), in anaerobic digestion of waste activated sludge aided by biochar. Results showed that the co-addition of separated biochar and AHL achieved best methane production performance, with the maximal methane yield of 154.7 mL/g volatile suspended solids, which increased by 51.9%, 47.2%, 17.9%, and 39.4% respectively compared to that of control, AHL-loaded biochar, sole AHL, and sole biochar groups. The reason was that the co-addition of separated biochar and AHL promoted the stages of hydrolysis and acidification, promoting the conversion of organic matters and short-chain fatty acids, and optimizing the accumulation of acetate acid. Moreover, the methanogenesis stage also performed best among experimental groups. Correspondingly, the highest activities of electron transfer and coenzyme F420 were obtained, with increase ratios of 33.2% and 27.2% respectively compared to that of control. Furthermore, biochar did more significant effects on the evolution of microbial communities than AHL, and the direct interspecific electron transfer between fermentative bacteria and methanogens were possibly promoted.
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Carbón Orgánico , Metano , Percepción de Quorum , Metano/metabolismo , Anaerobiosis , Aguas del Alcantarillado , Ácidos Grasos Volátiles/metabolismo , Acil-Butirolactonas/metabolismoRESUMEN
In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.
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Aprobación de Drogas , United States Food and Drug Administration , Humanos , Estados Unidos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Estructura MolecularRESUMEN
To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH4/g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolutions of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiies of electron transfer and the contents of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD.
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Carbón Orgánico , Sustancias Húmicas , Metano , Carbón Orgánico/química , Carbón Orgánico/farmacología , Anaerobiosis , Metano/metabolismo , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Reactores BiológicosRESUMEN
Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.
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Estrés del Retículo Endoplásmico , Regulación de la Expresión Génica de las Plantas , Glycine max , Proteínas de Plantas , Especies Reactivas de Oxígeno , Factores de Transcripción , Glycine max/genética , Estrés del Retículo Endoplásmico/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Peroxidasa/metabolismo , Peroxidasa/genéticaRESUMEN
Phosphorus is one of the important factors to successfully establish the microalgal-bacterial symbiosis (MABS) system. The migration and transformation of phosphorus can occur in various ways, and the effects of phosphate on the MABS system facing environmental impacts like heavy metal stress are often ignored. This study investigated the roles of phosphate on the response of the MABS system to zinc ion (Zn2+). The results showed that the pollutant removal effect in the MABS system was significantly reduced, and microbial growth and activity were inhibited with the presence of Zn2+. When phosphate and Zn2+ coexisted, the inhibition effects of pollutants removal and microbial growth rate were mitigated compared to that of only with the presence of Zn2+, with the increasing rates of 28.3% for total nitrogen removal, 48.9% for chemical oxygen demand removal, 78.3% for chlorophyll-a concentration, and 13.3% for volatile suspended solids concentration. When phosphate was subsequently supplemented in the MABS system after adding Zn2+, both pollutants removal efficiency and microbial growth and activity were not recovered. Thus, the inhibition effect of Zn2+ on the MABS system was irreversible. Further analysis showed that Zn2+ preferentially combined with phosphate could form chemical precipitate, which reduced the fixation of MABS system for Zn2+ through extracellular adsorption and intracellular uptake. Under Zn2+ stress, the succession of microbial communities occurred, and Parachlorella was more tolerant to Zn2+. This study revealed the comprehensive response mechanism of the co-effects of phosphate and Zn2+ on the MABS system, and provided some insights for the MABS system treating wastewater containing heavy metals, as well as migration and transformation of heavy metals in aquatic ecosystems.
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Metales Pesados , Microalgas , Fosfatos , Simbiosis , Aguas Residuales , Contaminantes Químicos del Agua , Metales Pesados/metabolismo , Aguas Residuales/química , Fosfatos/farmacología , Fosfatos/metabolismo , Eliminación de Residuos Líquidos/métodos , Bacterias/metabolismo , Bacterias/efectos de los fármacos , ZincRESUMEN
Alleviating the decomposition of the electrolyte is of great significance to improving the cycle stability of cathodes, especially for LiCoO2 (LCO), its volumetric energy density can be effectively promoted by increasing the charge cutoff voltage to 4.6 V, thereby supporting the large-scale application of clean energy. However, the rapid decomposition of the electrolyte under 4.6 V conditions not only loses the transport carrier for lithium ion, but also produces HF and insulators that destroy the interface of LCO and increase impedance. In this work, the decomposition of electrolyte is effectively suppressed by changing the adsorption force between LCO interface and EC. Density functional theory illustrates the LCO coated with lower electronegativity elements has a weaker adsorption force with the electrolyte, the adsorption energy between LCO@Mg and EC (0.49 eV) is weaker than that of LCO@Ti (0.73 eV). Meanwhile, based on the results of time of flight secondary ion mass spectrometry, conductivity-atomic force microscopy, in situ differential electrochemical mass spectrometry, soft X-ray absorption spectroscopy, and nuclear magnetic resonance, as the adsorption force increases, the electrolyte decomposes more seriously. This work provides a new perspective on the interaction between electrolyte and the interface of cathode and further improves the understanding of electrolyte decomposition.
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Since Na3V2(PO4)3 (NVP) possesses modest volume deformation and three-dimensional ion diffusion channels, it is a potential sodium-ion battery cathode material that has been extensively researched. Nonetheless, NVP still endures the consequences of poor electronic conductivity and low voltage platforms, which need to be further improved. On this basis, a high voltage platform Na3V2(PO4)2F3 was introduced to form a composite with NVP to increase the energy density. In this study, the sol-gel technique was successfully used to synthesize a Na3V2(PO4)2.75F0.75/C (NVPF·3NVP/C) composite cathode material. The citric acid-derived carbon layer was utilized to construct three-dimensional conducting networks to effectively promote ion and electron diffusion. Furthermore, the composites' synergistic effect accelerates the quick ionic migration and improves the kinetic reaction. In particular, NVP as the dominant phase enhanced the structural stability and significantly increased the capacitive contribution. Therefore, at 0.1C, the discharge capacity of the modified NVPF·3NVP/C composite is 120.7 mA h g-1, which is greater than the theoretical discharge capacity of pure NVP (118 mA h g-1). It discharged 110.9 mA h g-1 of reversible capacity even at an elevated multiplicity of 10C, and after 200 cycles, it retained 64.1% of its capacity. Thus, the effort produced an optimized NVPF·3NVP/C composite cathode material that may be used in the sodium ion cathode.
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Biochar produced from bio-wastes has been widely used to promote the performance of anaerobic digestion. Waste activated sludge (WAS) is considered as a kind of popular precursor for biochar preparation, but the abundant resources in WAS were neglected previously. In this study, the roles of biochar prepared from raw, pretreated, and fermented sludge on anaerobic digestion were investigated. That is, parts of carbon sources and nutrients like polysaccharides, proteins, and phosphorus were firstly recovered after sludge pretreatment or fermentation, and then the sludge residuals were used as raw material to prepare biochar. The methane yield improved by 22.1% with adding the biochar (AK-BC) prepared by sludge residual obtained from alkaline pretreatment. Mechanism study suggested that the characteristics of AK-BC like specific surface area and defect levels were updated. Then, the conversion performance of intermediate metabolites and electro-activities of extracellular polymeric substances were up-regulated. As a result, the activity of electron transfer was increased with the presence of AK-BC, with increase ratio of 21.4%. In addition, the electroactive microorganisms like Anaerolineaceae and Methanosaeta were enriched with the presence of AK-BC, and the potential direct interspecies electron transfer was possibly established. Moreover, both aceticlastic and CO2-reducing methanogenesis pathways were improved by up-regulating related enzymes. Therefore, the proposed strategy can not only obtain preferred biochar but also recover abundant resources like carbon source, nutrients, and bioenergy.
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Carbón Orgánico , Metano , Aguas del Alcantarillado , Carbón Orgánico/química , Aguas del Alcantarillado/química , Aguas del Alcantarillado/microbiología , Anaerobiosis , Metano/metabolismo , Eliminación de Residuos Líquidos/métodos , Álcalis/química , Reactores BiológicosRESUMEN
Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals.
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Ascomicetos , Neoplasias Ováricas , Sesquiterpenos Policíclicos , Sesquiterpenos , Humanos , Femenino , Línea Celular Tumoral , Nucleósidos , Neoplasias Ováricas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/química , Ascomicetos/metabolismo , ApoptosisRESUMEN
V5S8 has received extensive attention in the field of sodium-ion batteries (SIBs) due to its two-dimensional (2D) layered structure, and weak van der Waals forces between V-S accelerate the transport of sodium ions. However, the long-term cycling of V5S8 still suffers from volume expansion and low conductivity. Herein, a hollow nanotube V5S8@C (H-V5S8@C) with improved conductivity was synthesized by a solvothermal method to alleviate cracking caused by volume expansion. Benefiting from the large specific surface area of the hollow nanotube structure and uniform carbon coating, H-V5S8@C exhibits a more active site and enhanced conductivity. Meanwhile, the heterojunction formed by a few residual MoS2 and the outer layer of V5S8 stabilizes the structure and reduces the ion migration barrier with fast Na+ transport. Specifically, the H-V5S8@C anode provides an enhanced rate performance of 270.1 mAh g-1 at 15 A g-1 and high cycling stability of 291.7 mAh g-1 with a retention rate of 90.98% after 300 cycles at 5 A g-1. This work provides a feasible approach for the structural design of 2D layered materials, which can promote the practical application of fast-charging sodium-ion batteries.
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Terminal drought is one of the major constraints to crop production in chickpea (Cicer arietinum L.). In order to map drought tolerance related traits at high resolution, we sequenced multi-parent advanced generation intercross (MAGIC) population using whole genome resequencing approach and phenotyped it under drought stress environments for two consecutive years (2013-14 and 2014-15). A total of 52.02 billion clean reads containing 4.67 TB clean data were generated on the 1136 MAGIC lines and eight parental lines. Alignment of clean data on to the reference genome enabled identification of a total, 932,172 of SNPs, 35,973 insertions, and 35,726 deletions among the parental lines. A high-density genetic map was constructed using 57,180 SNPs spanning a map distance of 1606.69 cM. Using compressed mixed linear model, genome-wide association study (GWAS) enabled us to identify 737 markers significantly associated with days to 50% flowering, days to maturity, plant height, 100 seed weight, biomass, and harvest index. In addition to the GWAS approach, an identity-by-descent (IBD)-based mixed model approach was used to map quantitative trait loci (QTLs). The IBD-based mixed model approach detected major QTLs that were comparable to those from the GWAS analysis as well as some exclusive QTLs with smaller effects. The candidate genes like FRIGIDA and CaTIFY4b can be used for enhancing drought tolerance in chickpea. The genomic resources, genetic map, marker-trait associations, and QTLs identified in the study are valuable resources for the chickpea community for developing climate resilient chickpeas.
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Cicer , Mapeo Cromosómico , Cicer/genética , Genoma de Planta , Estudio de Asociación del Genoma Completo , Resistencia a la SequíaRESUMEN
BACKGROUND: Endovascular treatment for patients with symptomatic nonacute middle cerebral artery occlusion remains clinically challenging, and proof of a beneficial effect on functional outcome is lacking. We aim to evaluate the effectiveness and safety of endovascular recanalization for patients with symptomatic nonacute middle cerebral artery occlusion. METHODS: Ninety-eight patients with symptomatic atherosclerotic nonacute middle cerebral artery occlusion were divided into drug treatment groups (42) and endovascular treatment groups (56). The rate of recanalization, peri-procedural complications, and follow-up results were evaluated. RESULTS: Among the 56 patients who received endovascular treatment, 53 (94.6%) achieved successful recanalization. The rate of peri-procedural complications was 7.1% (4/56), and the death rate was 1.8% (1/56). Any stroke within 90 days was 7.1% (4/56). Among the 42 patients in drug treatment group, any stroke within 90 days was 19.0% (8/42), death rate was 0. CONCLUSION: Among patients with symptomatic nonacute middle cerebral artery occlusion with a short length of occlusion and a moderate-to-good collateral circulation, endovascular treatment seems to be safe. And endovascular treatment could reduce the recurrence rate of stroke.
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Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Resultado del Tratamiento , Accidente Cerebrovascular/terapia , Procedimientos Endovasculares/métodos , Estudios RetrospectivosRESUMEN
Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.
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Alstroemeria , Alternaria , Alternaria/genética , Metabolismo Secundario , Flavonoides/metabolismo , EndófitosRESUMEN
Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced,which provided reference for the research and development of sprays.
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Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.
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Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was (8.41±2.15) and (8.86±2.83) h·ng·ml−1, respectively; Cmax was (10.96±2.62) and (6.36±2.14) ng/ml, respectively; tmax was (0.18±0.05) and (0.58±0.24) h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.
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Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18(2) (4.6 mm × 250 mm, 5 µm) column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .
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Objective To evaluate the value of magnetic resonance imaging(MRI)in prenatal diagnosis of fetal Chiari malformation.Methods The prenatal MRI findings of 27 cases of Chiari malformation confirmed by follow-up in Obstetrics and Gynecology Hospital,Fudan University from Feb 2010 to Feb 2022 were retrospectively analyzed and compared with ultrasound findings.Results Twenty-seven pregnant women,aged from 16-36 years(average 28.0 years)and 27 fetuses with gestation from 15.3-38.4 weeks(average 24.3 weeks)were studied.There were 18 cases of Chiari Ⅱ(Chiari malformation type Ⅱ,CMⅡ),3 cases of Chiari Ⅲ(CMⅢ),6 cases of Chiari Ⅳ(CMⅣ).CMⅡ and CMⅢ images showed brain herniation,descending pons,narrowing or disappearance of the posterior fossa cistern and the fourth ventricle,the subarachnoid space disappears.There were 17 cases of hydrocephalus,2 cases of cerebrospinal fluid loss,17 cases of"lemon head"and"banana cerebellar"signs,4 cases of encephalocele,15 cases of spinal bifida,3 cases of lower spinal cord and 2 cases of spinal cavity,4 cases of spinal angular deformity and 6 cases of other malformations.In CMⅣ,there were 2 cases of undeveloped cerebellum and 4 cases of cerebellum and brainstem dysplasia,hydrocephalus in 5 cases,posterior fossa cistern widening in 4 cases,and other malformations in 4 cases.MRI showed the posterior fossa structure and spinal cord more clearly than ultrasound,and could find lesions not detected by ultrasound.Conclusion Prenatal MRI can be used as a complementary examination of ultrasound,which can improve the accuracy of diagnosis of Chiari malformation,reduce the rate of missed diagnosis,and clarify the classification of Chiari malformation.