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1.
Eur J Med Chem ; 278: 116811, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39217859

ABSTRACT

Pyridazinone derivatives have been extensively used as anticancer agents. IMB5036 is a structure specific pyridazinone compound with potential antitumor activity via targeting KSRP protein which controls gene expression at multiple levels. In this study, fifteen IMB5036 analogues were synthesized and preliminary structure-activity relationships were explored. Among them, compounds 8 and 10 exhibited remarkably anti-proliferation of various cancer cells and a good cancer cell selectivity (against human fetal hepatocyte L02 cells). More detailed investigation was included that both 8 and 10 inhibited colony formation and migration in concentration-dependent mode against MCF-7 cells. Additionally, 8 and 10 induced apoptosis and cell cycle arrest, decreased mitochondrial membrane potential, damaged DNA, and increased reactive oxygen species. Moreover, 8 displayed a potent antitumor efficacy (TGI = 74.2 %, at a dose of 30 mg/kg) in MCF-7 xenograft model by i.p. injection. Further, we synthesized a biotinylated probe 16 for identifying the detail domain of KSRP. Through pull down assay and molecular docking study, we validated that the KH23 domain functioned as the binding pocket for the compounds. Thus, compound 8 was identified as a novel targeting KSRP pyridazinone-based compound and exhibited excellent antitumor activity both in vitro and in vivo.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Drug Screening Assays, Antitumor , Pyridazines , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Pyridazines/pharmacology , Pyridazines/chemistry , Pyridazines/chemical synthesis , Cell Proliferation/drug effects , Structure-Activity Relationship , Animals , Apoptosis/drug effects , Mice , Molecular Structure , Dose-Response Relationship, Drug , Molecular Docking Simulation , Female , Mice, Nude , Mice, Inbred BALB C , Cell Line, Tumor
2.
Plant Divers ; 46(4): 435-447, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39280969

ABSTRACT

Gastrochilus is an orchid genus containing 73 species of mainly epiphytic on trees or rocks in mountain forests of tropical and subtropical Asia. Previous phylogenetic analyses and morphological assessments have failed to produce a well-resolved phylogeny at the infrageneric level. In the present study, a new infrageneric classification of Gastrochilus is proposed based on thoroughly morphological and phylogenetic analyses based on 52 species. Our phylogenetic analysis divided the genus into six sections including three new sections, G. sect. Pseudodistichi, G. sect. Brachycaules and G. sect. Acinacifolii. We also reinstate G. suavis to the specific rank. Furthermore, two new species, G. armeniacus Jun Y. Zhang, B. Xu & Yue H. Cheng and G. minjiangensis Jun Y. Zhang, B. Xu & Yue H. Cheng, are described and illustrated. A key to six sections of the genus is presented.

3.
Mitochondrial DNA B Resour ; 9(9): 1223-1226, 2024.
Article in English | MEDLINE | ID: mdl-39291127

ABSTRACT

Lilium saccatum is a species of ornamental plant found in southeastern Xizang, China. In the present study, the complete chloroplast (cp) genome of L. saccatum was sequenced using next-generation sequencing (NGS). The de novo assembled cp genome was 151,839 bp in length, including a pair of inverted repeat regions (IRs; 26,421 bp), a small single-copy region (SSC; 17,528 bp), and a large single-copy region (LSC; 81,469 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. The total GC content of the cp genome was 37.0%. Phylogenetic analysis of 24 cp genomes revealed that L. saccatum was closely related to L. souliei. This study could provide fundamental information for the phylogenomics and utilization of Lilium.

4.
Oncoscience ; 11: 69-91, 2024.
Article in English | MEDLINE | ID: mdl-39318358

ABSTRACT

Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.

5.
Eur J Pharmacol ; 983: 176968, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39233039

ABSTRACT

Compound 5p is a 4ß-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn't show the inhibitor of topoisomerase I. 5p exhibited the inhibitory effect on microtubule polymerization. 5p showed potent anti-proliferation against breast cancer, oral squamous carcinoma, and their drug-resistant cell lines, with resistance index of 0.61 and 0.86, respectively. 5p downregulated the expression levels of P-gp in KBV200 cells and BCRP in MCF7/ADR cells in dose-dependent manner. Moreover, 5p induced KB and KBV200 cells arrest at G2/M phase by up-regulating the expression of γ-H2AX, p-Histone H3 and cyclin B1. 5p induced apoptosis and pyroptosis by increased the expression levels of cleaved-PARP, cleaved-caspase3, N-GSDME as well as LDH release in KB and KBV200 cells. In addition, 5p efficiently impaired tumor growth in KB and KBV200 xenograft mice. Conclusively, this work elucidated the dual inhibitor of topoisomerase II and microtubule of 5p and its mechanism of overcoming the multidrug resistance, indicating that 5p exerts the antitumor potentiality.

6.
Biochem Biophys Res Commun ; 734: 150616, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39232456

ABSTRACT

Cisplatin (DDP) resistance in advanced stages of ovarian cancer significantly reduces survival rates. Mitochondria may serve as a potential therapeutic target for ovarian cancer. Pal-pHK-pKV is a mitochondrial targeting peptide synthesized by supramolecular assembly. Our study aims to investigate whether Pal-pHK-pKV serves as a useful strategy to reverse DDP resistance in ovarian cancer. Subcutaneous tumor implantation of the DDP-resistant ovarian cancer cell line A2780CP was conducted in nude mice, and drugs were administered intraperitoneally to compare the inhibitory effects of Pal-pHK-pKV and DDP on A2780CP cells in vivo. Combination index values were calculated for various concentrations of DDP and Pal-pHK-pKV to determine the optimal combination concentration. Mitochondrial membrane potential, cytochrome C distribution and immunofluorescence were also measured. Our studies demonstrated that Pal-pHK-pKV treatment reduced the proliferation, invasion and metastasis of ovarian cancer cells and impaired mitochondrial function. Furthermore, the combination of Pal-pHK-pKV and DDP exhibited a synergistic effect. Mechanistically, Pal-pHK-pKV can impair mitochondrial function, reduce mitochondrial membrane potential and release ROS. On the other hand, Pal-pHK-pKV can affect ERK pathway activation and inhibit tumor development. In conclusion, the mitochondria-specific amphiphilic peptide Pal-pHK-pKV provides a novel approach for treating ovarian cancer and may potentially overcome DDP drug resistance.

7.
Postgrad Med J ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39251231

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, the emergence of ICI-associated myocarditis (ICI-MC) presents a severe and potentially fatal complication with poorly understood pathophysiological mechanisms. This study aimed to identify crucial immune-related genes in ICI-MC and uncover potential therapeutic targets using bioinformatics. METHODS: Using the GSE180045 dataset, which includes three groups-Group A: ICI patients without immune adverse events, Group B: ICI patients with non-myocarditis immune adverse events, and Group C: ICI patients with myocarditis-we analyzed differentially expressed genes (DEGs) between ICI-MC samples (Group C) and non-myocarditis controls (Groups A and B). These DEGs were then cross-referenced with 1796 immune-related genes from the immPort database to identify immune-related DEGs. We conducted functional enrichment analyses (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis), constructed a protein-protein interaction network, and identified hub genes. Validation using the GSE4172 dataset led to the identification of optimal feature genes from the overlap between hub genes and DEGs. Predictions of target MicroRNAs (miRNAs) were made, and a competing endogenous RNA (ceRNA) network was constructed. Target drugs for hub genes were predicted using the Connectivity Map database. RESULTS: We identified 58 DEGs between ICI-MC and controls, which led to the identification of 32 immune-related DEGs after intersection with 1796 immune-related genes. Functional analyses revealed enrichment in cell lysis, CD8+ T-cell receptor, natural killer cell-mediated cytotoxicity, and RAGE signaling. Notably upregulated hub genes included IL7R, PRF1, GNLY, CD3G, NKG7, GZMH, GZMB, KLRB1, KLRK1, and CD247. In the validation dataset, 407 DEGs were uncovered, resulting in the identification of 3 optimal feature genes (KLRB1, NKG7, GZMH). The predicted target miRNAs, lincRNAs, and circRNAs constituted a comprehensive ceRNA network. Among the top 10 drugs with elevated connectivity scores was acetohydroxamic acid, indicating a need for caution in ICI treatment. CONCLUSION: KG7, GZMH, and KLRB1 were identified as pivotal immune-related genes in ICI-MC. Biological enrichments included pathways involved in cell lysis, the CD8+ T-cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory responses. The ceRNA network illuminated the role of critical molecules and underscored the importance of avoiding drugs such as acetohydroxamic acid in ICI treatment. Key message What is already known on this topic  Myocarditis is recognized as a serious ICI-associated toxicity, seemingly infrequent yet often fulminant and lethal. The underlying mechanisms of ICI-associated myocarditis remain not fully understood. Although the significance of T cells and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is evident, the inciting antigens, the reasons for their recognition, and the mechanisms causing cardiac cell injury are not well characterized. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems. What this study adds  Our study further validates the significance of T cells and CTLA-4 in ICI-associated myocarditis. More importantly, we identified three genes-NKG7, GZMH, and KLRB1-essential for the development of ICI-MC and proposed ceRNA networks involving these three key genes. How this study might affect research, practice or policy  The newly discovered key genes and their intricate molecular interactions offer a comprehensive perspective on the mechanisms underlying ICI-MC. Furthermore, our findings advise caution regarding the use of drugs like acetohydroxamic acid during ICI treatment. As our understanding of these regulatory networks deepens, our study provides valuable insights that could inform future therapeutic strategies for ICI-MC.

8.
Thromb J ; 22(1): 73, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39118154

ABSTRACT

BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas. METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People's Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups. RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively. CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

9.
Article in English | MEDLINE | ID: mdl-39052058

ABSTRACT

Geniposide (GE), a bioactive compound extracted from the fruit of Gardenia jasminoides Ellis, has attracted significant attention for its hepatoprotective therapeutic applications. Although GE displays a protective effect on treating intrahepatic cholestasis (IC), the underlying mechanism remains elusive. In this study, we aimed to elucidate the pharmacological mechanisms of GE in treating IC by an integrated analysis of transcriptomics and metabolomics. Firstly, we evaluated the hepatoprotective effect of GE in α-naphthylisothiocyanate (ANIT)-induced IC rats by examining biochemical indices, inflammatory factors, and oxidative stress levels. Secondly, by transcriptomics and serum metabolomics, we identified differentially expressed genes and metabolites, revealing phenotype-related metabolic pathways and gene functions. Lastly, we screened the core targets of GE in the treatment of IC by integrating transcriptomic and metabolomic data and validated these targets using western blotting. The results indicated that GE improved serum indexes and alleviated inflammation reactions and oxidative stress in the liver. The transcriptomics analysis revealed 739 differentially expressed genes after GE treatment, mainly enriched in retinol metabolism, steroid hormone synthesis, PPAR signal transduction, bile secretion metabolism, and other pathways. The metabolomics analysis identified 98 differential metabolites and 10 metabolic pathways. By constructing a "genes-targets-pathways-compounds" network, we identified two pathways: the bile secretion pathway and the glutathione pathway. Within these pathways, we discovered nine crucial targets that were subsequently validated through western blotting. The results revealed that the GE group significantly increased the expression of ABCG5, NCEH1, OAT3, and GST, compared with the ANIT group. We speculate that GE has a therapeutic effect on IC by modulating the bile secretion pathway and the glutathione pathway and regulating the expression of ABCG5, NCEH1, OAT3, and GST.

10.
Foods ; 13(14)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39063314

ABSTRACT

The volatile compounds in strawberries play a significant role in the formation of strawberry aroma. However, these compounds undergo continual changes during storage, resulting in a decline in quality. In this study, a total of 67 volatile organic compounds (VOCs) were identified in strawberries through quantitative analysis. At the end of the storage period, the VOC content in the ultrasonic group was 119.02 µg/kg higher than that in the control group. The results demonstrated that the ultrasonic treatment increased the contents of terpenes and esters at the end of storage. Among these, linalool increased from 67.09 to 91.41 µg/kg, while ethyl cinnamate increased from 92.22 to 106.79 µg/kg. Additionally, the expression of the key metabolic genes closely related to these substances was significantly up-regulated. The expression of the FaNES gene, related to terpene metabolism, was up-regulated by 2.8 times in the second day, while the expression of the FaAAT gene, related to ester metabolism, was up-regulated by 1.5 times. In summary, this study provides a theoretical basis for exploring the mechanism of ultrasonic effect on strawberry flavor and quality after harvest.

11.
Int J Nanomedicine ; 19: 6693-6715, 2024.
Article in English | MEDLINE | ID: mdl-38979534

ABSTRACT

Colorectal cancer (CRC) is a common type of gastrointestinal tract (GIT) cancer and poses an enormous threat to human health. Current strategies for metastatic colorectal cancer (mCRC) therapy primarily focus on chemotherapy, targeted therapy, immunotherapy, and radiotherapy; however, their adverse reactions and drug resistance limit their clinical application. Advances in nanotechnology have rendered lipid nanoparticles (LNPs) a promising nanomaterial-based drug delivery system for CRC therapy. LNPs can adapt to the biological characteristics of CRC by modifying their formulation, enabling the selective delivery of drugs to cancer tissues. They overcome the limitations of traditional therapies, such as poor water solubility, nonspecific biodistribution, and limited bioavailability. Herein, we review the composition and targeting strategies of LNPs for CRC therapy. Subsequently, the applications of these nanoparticles in CRC treatment including drug delivery, thermal therapy, and nucleic acid-based gene therapy are summarized with examples provided. The last section provides a glimpse into the advantages, current limitations, and prospects of LNPs in the treatment of CRC.


Subject(s)
Colorectal Neoplasms , Nanoparticles , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/therapy , Nanoparticles/chemistry , Lipids/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Genetic Therapy/methods , Drug Delivery Systems/methods , Liposomes
12.
Mol Phylogenet Evol ; 199: 108138, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38977041

ABSTRACT

Cypripedioideae (slipper orchids; Orchidaceae) currently consist of âˆ¼200 herbaceous species with a strikingly disjunctive distribution in tropical and temperate regions of both hemispheres. In this study, an updated phylogeny with representatives from all five cypripedioid genera was presented based on maximum likelihood and Bayesian inference of plastome and low-copy nuclear genes. Phylogenomic analyses indicated that each genus is monophyletic, but some relationships (e.g., those among Cypripedium sects. Acaulia, Arietinum, Bifolia, Flabellinervia, Obtusipetala and Palangshanensia) conflict with those in previous studies based on Sanger data. Cypripedioideae appeared to have arisen in South America and/or the adjacent Qinghai-Tibet Plateau and Hengduan Mountains âˆ¼35 Mya. We inferred multiple dispersal events between East Asia and North America in Cypripedium, and between mainland Southeast Asia and the Malay Archipelago in Paphiopedilum. In the Americas, divergences among four genera (except Cypripedium) occurred around 31-20 Mya, long before the closure of the Isthmus of Panama, indicating the importance of long-distance dispersal. Evolutionary patterns between morphological and plastome character evolution suggested several traits, genome size and NDH genes, which are likely to have contributed to the success of slipper orchids in alpine floras and low-elevation forests. Species diversification rates were notably higher in epiphytic clades of Paphiopedilum than in other, terrestrial cypripedioids, paralleling similar accelerations associated with epiphytism in other groups. This study also suggested that sea-level fluctuations and mountain-building processes promoted the diversification of the largest genera, Paphiopedilum and Cypripedium.


Subject(s)
Orchidaceae , Phylogeny , Phylogeography , Orchidaceae/genetics , Orchidaceae/classification , Bayes Theorem , Evolution, Molecular , Genetic Speciation , Biological Evolution , Sequence Analysis, DNA
13.
J Environ Manage ; 367: 121851, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39067342

ABSTRACT

A significant body of research has documented the profound changes in global atmospheric conditions during the COVID-19 pandemic. However, there is still an inadequate comprehensive comparison and assessment of countries before, during, and after the pandemic. Variations in restriction policies, human behaviors, and national traits lead to significant differences in how restriction policies affect atmospheric pollution. This study focuses on NO2, a pollutant with high temporal sensitivity, and utilizes the Oxford COVID-19 policy stringency index along with demographic information. Through spatial-temporal mapping, we analyzed NO2 emission fluctuations and calculated the emission changes in each country. Drawing from this analysis, we explored the relationships among these factors and found that over the span of 2019-2022, across 193 countries, global NO2 emissions displayed a distinct trajectory: initially decreasing, subsequently rebounding, and eventually fluctuating. Most countries exhibited seasonal variations in NO2 emissions. Additionally, the study uncovered a correlation between the stringency of COVID-19 policies and the reduction in NO2 emissions: as policies became stricter, emissions significantly decreased in most countries. In contrast, in countries with lower population densities, stricter policies paradoxically led to an increase in emissions. These findings underscore the importance of considering demographic factors and geographical context in the formulation and implementation of environmental policies.


Subject(s)
COVID-19 , Environmental Monitoring , Nitrogen Dioxide , Nitrogen Dioxide/analysis , Humans , Environmental Monitoring/methods , Air Pollution/analysis , Air Pollutants/analysis , SARS-CoV-2 , Remote Sensing Technology , Pandemics , Environmental Policy
14.
Food Chem ; 453: 139558, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38781892

ABSTRACT

The effect of moisture content changes during drying processing on the appearance of sea buckthorn was studied. Using computer vision methods and various image processing methods to collect and analyze images during the drying process of sea buckthorn fruit. Sea buckthorn is dried in a drying oven at a temperature of 65 °C and Level 1 wind speed conditions. The images of the entire drying process of sea buckthorn fruit were collected at 30-min intervals. Deep mining and transformation of image information through various image processing methods. By calibrating and modeling the color components, real-time online detection of the moisture content of sea buckthorn fruit can be achieved. After modeling, this article attempted to use LSTM (Long Short Term Memory) to predict the appearance of sea buckthorn fruit with supercritical moisture content. Different agricultural products adapt to different color spaces, but after standard modeling with a certain amount of data, applying color components to detect moisture content is a very good method.


Subject(s)
Fruit , Hippophae , Image Processing, Computer-Assisted , Water , Hippophae/chemistry , Fruit/chemistry , Water/analysis , Water/chemistry , Image Processing, Computer-Assisted/methods , Color , Desiccation/methods
15.
Chemosphere ; 360: 142325, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38754489

ABSTRACT

Enhancing the kinetic performance of thick electrodes is essential for improving the efficiency of lithium extraction processes. Biochar, known for its affordability and unique three-dimensional (3D) structure, is utilized across various applications. In this study, we developed a biochar-based, 3D-conductive network thick electrode (∼20 mg cm-2) by in-situ deposition of LiFePO4 (LFP) onto watermelon peel biomass (WB). Utilizing Density Functional Theory (DFT) calculations complemented by experimental data, we confirmed that this The thick electrode exhibits outstanding kinetic properties and a high capacity for lithium intercalation in brines, even in environments where the Magnesia-lithium ratios are significantly high. The electrode showed an impressive intercalation capacity of 30.67 mg g-1 within 10 min in a pure lithium solution. It also maintained high intercalation performance (31.17 mg g-1) in simulated brines with high Magnesia-lithium ratios. Moreover, in actual brine, it demonstrated a significant extraction capacity (23.87 mg g-1), effectively lowering the Magnesia-lithium ratio from 65 to 0.50. This breakthrough in high-conductivity thick electrode design offers new perspectives for lithium extraction technologies.


Subject(s)
Charcoal , Electrodes , Lithium , Lithium/chemistry , Lithium/isolation & purification , Charcoal/chemistry , Lakes/chemistry , Magnesium/chemistry , Citrullus/chemistry , Salts/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Kinetics , Iron , Phosphates
16.
Eur J Med Chem ; 273: 116509, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38781920

ABSTRACT

A series of novel carbazole sulfonamide derivatives were synthesized and evaluated for antiproliferative activity. Among them, compounds 7 and 15 showed strong potency (IC50 values of 0.81-31.19 nM) against five different cancer cells including multidrug-resistant MCF7/ADR cells. Compound 15 displayed a high cancer cell selectivity (IC50(L02)/average IC50: SI = 7.7). The l-valine prodrug 7a and the phosphate prodrug 15a exerted rohust in vivo antitumor efficacies and accepted safety prolifes. Further mechanism studies revealed that 7 and 15 directly bind to the colchicine site in tubulin to block tubulin polymerization, promote microtubule fragmentation at the cellular level, and induce apoptosis with G2/M cell cycle arrest. These compounds also inhibit HEMC-1 cells migration and vascular tube formation. Additionally, compound 7 displayed a selective inhibition of Topo I. Collectively, these studies suggest that 7 and 15 represents a promising new generation of tubulin inhibitors for cancer treatment.


Subject(s)
Antineoplastic Agents , Apoptosis , Carbazoles , Cell Proliferation , Drug Screening Assays, Antitumor , Sulfonamides , Tubulin Modulators , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Carbazoles/pharmacology , Carbazoles/chemistry , Carbazoles/chemical synthesis , Structure-Activity Relationship , Sulfonamides/pharmacology , Sulfonamides/chemistry , Sulfonamides/chemical synthesis , Cell Proliferation/drug effects , Apoptosis/drug effects , Molecular Structure , Tubulin Modulators/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/chemical synthesis , Tubulin/metabolism , Dose-Response Relationship, Drug , Cell Line, Tumor , Animals , Cell Movement/drug effects , Mice
17.
Chem Asian J ; 19(15): e202400436, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38753576

ABSTRACT

Prolonging the lifetime of SAPO-34 catalysts and enhancing their olefin selectivity in methanol-to-olefin (MTO) reactions are critical yet challenging objectives. Here, a series of hierarchical SAPO-34 catalysts were synthesized using a straightforward recrystallization method. The incorporation of triethylamine into the recrystallization mother liquor facilitated the formation of mesopores, achieving a high solid yield of up to 90%. Notably, the addition of phosphoric acid and ammonium polyvinyl phosphate alcohol during the recrystallization process significantly enhanced the crystallinity and regularity of the hierarchical SAPO-34 crystals, consequently increasing the mesopore size. Due to the substantially improved mass transfer efficiency and moderated acidity, the SP34-0.14P-0.06R catalysts exhibited a prolonged lifetime of 344 min and 80.3% selectivity for ethylene and propylene at a weight hourly space velocity (WHSV) of 2 h-1. This performance markedly surpasses that of the parent SP34 catalyst, which demonstrated a lifetime of 136 min and a selectivity of 78.0%. Remarkably, the SP34-0.14P-0.06R maintained a lifetime of 166 min even at a high WHSV of 10 h-1, which is more than 5-fold greater than that of the original microporous SP34. This research offers valuable insights into the design and development of hierarchically porous zeolites with high yields, enhancing the efficiency of MTO reactions and other applications.

18.
Langmuir ; 40(17): 9144-9154, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38629776

ABSTRACT

Wastewater pollutants are a major threat to natural resources, with antibiotics and heavy metals being common water contaminants. By harnessing clean, renewable solar energy, photocatalysis facilitates the synergistic removal of heavy metals and antibiotics. In this paper, MXene was both a template and raw material, and MXene-derived oxide (TiO2) and SnIn4S8 Z-scheme composite materials were synthesized and characterized. The synergistic mode of photocatalytic reduction and oxidation leads to the enhanced utilization of e-/h+ pairs. The TiO2/SnIn4S8 exhibited a higher photocatalytic capacity for the simultaneous removal of tetracycline (TC) (20 mg·L-1) and Cr(VI) (15 mg·L-1). The main active substances of TC degradation and Cr(VI) reduction were identified via free radical scavengers and electron paramagnetic resonance (EPR). Additionally, the potential photocatalytic degradation route of TC was thoroughly elucidated through liquid chromatography-mass spectrometry (LC-MS).

19.
Opt Lett ; 49(7): 1648-1651, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38560827

ABSTRACT

High-frequency (greater than 30 MHz) photoacoustic computed tomography (PACT) provides the opportunity to reveal finer details of biological tissues with high spatial resolution. To record photoacoustic signals above 30 MHz, sampling rates higher than 60 MHz are required according to the Nyquist sampling criterion. However, the highest sampling rates supported by existing PACT systems are typically within the range of 40-60 MHz. Herein, we propose a novel PACT imaging method based on sub-Nyquist sampling. The results of numerical simulation, phantom experiment, and in vivo experiment demonstrate that the proposed imaging method can achieve high-frequency PACT imaging with a relatively low sampling rate. An axial resolution of 22 µm is achieved with a 30-MHz transducer and a 41.67-MHz sampling rate. To the best of our knowledge, this is the highest axial resolution ever achieved in PACT based on a sampling rate of not greater than 60 MHz. This work is expected to provide a practical way for high-frequency PACT imaging with limited sampling rates.

20.
Arq Bras Cardiol ; 121(1): e20230214, 2024.
Article in Portuguese, English | MEDLINE | ID: mdl-38422349

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. OBJECTIVES: The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%. METHODS: We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF. All tests were 2-sided; only the p-value <0.05 was considered statistically significant. RESULTS: We found that CA was associated with lower all-cause mortality (risk ratio: 0.52, 95% CI: 0.37 to 0.72; p<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29% to 7.31%; p<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18% to 6.88%; p<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87% to 3.16%; p<0.01). CONCLUSIONS: Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA.


FUNDAMENTO: A fibrilação atrial (FA) e a insuficiência cardíaca (IC) coexistem frequentemente, resultando em desfechos adversos. No entanto, permanecem controvérsias quanto à eficácia da ablação por cateter (AC) em pacientes com FA com disfunção ventricular esquerda grave. OBJETIVOS: O objetivo deste estudo foi realizar uma metanálise de ensaios prospectivos randomizados e controlados para avaliar a eficácia da AC versus terapia médica (TM) em pacientes com FA com fração de ejeção do ventrículo esquerdo (FEVE) ≤45%. MÉTODOS: Procuramos na literatura estudos que comparassem AC com TM em pacientes com FA com FEVE ≤45%. Foi realizada uma metanálise de 7 ensaios clínicos, incluindo 1.163 pacientes com FA e IC. A análise de subgrupo foi realizada com base na FEVE basal. Todos os testes foram bilaterais; apenas o valor p <0,05 foi considerado estatisticamente significativo. RESULTADOS: Descobrimos que a AC estava associada a menor mortalidade por todas as causas (taxa de risco: 0,52, IC 95%: 0,37 a 0,72; p<0,01) e maiores melhorias na FEVE (diferença média: 4,80%, IC 95%: 2,29% a 7,31%; p<0,01) em comparação com TM. Os pacientes do grupo AC apresentaram menor risco de hospitalização por IC e recorrência de FA e qualidade de vida significativamente melhor do que aqueles do grupo TM. Os resultados da análise de subgrupo indicaram que pacientes com disfunção ventricular esquerda mais leve melhoraram a FEVE após a ablação de FA (diferença média: 6,53%, IC 95%: 6,18% a 6,88%; p<0,01) em comparação com pacientes com doença mais grave (diferença média : 2,02%, IC 95%: 0,87% a 3,16%; p<0,01). CONCLUSÕES: Nossa metanálise demonstrou que a AC foi associada a melhorias significativas nos resultados de pacientes com FA com FEVE ≤45%. Além disso, pacientes com FA com disfunção ventricular esquerda mais leve poderiam se beneficiar mais com a AC.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Heart Failure , Ventricular Dysfunction, Left , Humans , Atrial Fibrillation/surgery , Stroke Volume , Ventricular Function, Left , Quality of Life , Prospective Studies , Treatment Outcome , Anti-Arrhythmia Agents/therapeutic use , Randomized Controlled Trials as Topic , Ventricular Dysfunction, Left/etiology , Catheter Ablation/methods
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