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1.
J Environ Sci (China) ; 150: 254-266, 2025 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39306401

RESUMO

Formaldehyde (HCHO) is a high-yield product of the oxidation of volatile organic compounds (VOCs) released by anthropogenic activities, fires, and vegetations. Hence, we examined the spatiotemporal variation trends in HCHO columns observed using the Ozone Monitoring Instrument (OMI) during 2005-2021 across the Fenwei Plain (FWP) and analysed the source and variability of HCHO using multi-source data, such as thermal anomalies. The spatial distribution of the annual mean HCHO in the FWP increased from northwest to southeast during 2005-2021, and the high-value aggregation areas contracted and gradually clustered, forming a belt-shaped distribution area from Xi'an to Baoji, north of the Qinling Mountains. The annual mean HCHO concentration generally showed a two-step increase over the 17 years. Fires showed a single-peak trend in March and a double-peak M-shaped trend in March and October, whereas urban thermal anomalies (UTAs) showed an inverted U-shaped trend over 17 years, with peaks occurring in May. The HCHO peaks are mainly caused by the alternating contributions of fires and UTAs. The fires and UTAs (predominantly industrial heat sources) played a role in controlling the background level of HCHO in the FWP. Precipitation and temperature were also important influencing variables for seasonal variations, and the influence of plant sources on HCHO concentrations had significant regional characteristics and contributions. In addition, the FWP has poor dispersion conditions and is an aggregated area for the long-range transport of air pollutants.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Formaldeído , Formaldeído/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , China , Compostos Orgânicos Voláteis/análise , Poluição do Ar/estatística & dados numéricos
2.
Inorg Chem ; 63(37): 17176-17187, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39222386

RESUMO

Elucidating the correlations between the core structure of atomically precise nanoclusters and their catalytic activities is fundamentalfor exploring highly efficient nanocatalysts. Herein, a series of Ag-based nanoclusters protected by 2,4-dimethylphenylthiophenol (specifically Ag4Pd2(SPhMe2)8 and Ag24M(SPhMe2)18 where M = Ag, Pd, and Pt) were synthesized and deposited on TiO2 supports as heterogeneous catalysts for the selective hydrogenation of nitroarenes with NaBH4 as the reductant. It was found that Ag4Pd2(SPhMe2)8 could spontaneously lose its ligands during catalysis, leading to the formation of polydispersed AgPd nanoparticles. This transformation endows the system with extraordinary activity for driving the hydrogenation of nitroarenes. However, the Ag24M (M = Ag, Pd, and Pt) systems, maintain their core structures during catalysis. They follow the generally reported ligand-mediated hydride-involved process, with catalytic activities depending on the central atom (Pt > Pd > Ag), which affects the hydride transferred from the nanoclusters to the reactant to regulate the catalysis.

3.
Sci Rep ; 14(1): 21043, 2024 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251712

RESUMO

1,4-Naphthoquinone scaffold-derived compounds has shown considerable pharmacological properties against cancer, including acute myeloid leukemia (AML) However, its impact and mechanisms in AML are uncertain. In this study, the mechanisms of 1,4-naphthoquinone scaffold-derived compounds against AML were investigated via network pharmacology, molecular docking and molecular dynamics simulation. ASINEX database was used to collect the 1,4-naphthoquinone scaffold-derived compounds, and compounds were extracted from the software to evaluate their drug similarity and toxicity. The potential targets of compounds were retrieved from the SwissTargetPrediction Database and the Similarity Ensemble Approach Database, while the potential targets of AML were obtained from the GeneCards databases and Gene Expression Omnibus. The STRING database was used to construct a protein-protein interaction (PPI) network, topologically and Cyto Hubb plugin of Cytoscape screen the central targets. After selecting the potential key targets, the gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the intersection targets, and a network map of "compounds-potential targets-pathway-disease" were constructed. Molecular docking of the compounds with the core target was performed, and core target with the strongest binding force and 1,4-naphthoquinone scaffold-derived compounds was selected for further molecular dynamics simulation and further molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) approach verification. In addition, the Bloodspot database was applied to perform the overall survival of core targets. A total of 19 1,4-naphthoquinone scaffold-derived compounds were chosen out, and then 836 targets of compounds, 96 intersection targets of AML were screened. Core targets include STAT3, TLR4, HSP90AA1, JUN, MMP9, PTPRC, JAK2, PTGS2, KIT and CSF1R. GO functional enrichment analysis revealed that 90 biological processes, 10 cell components and 12 molecular functions were enriched while KEGG pathway enrichment analysis revealed 34 enriched signaling pathways. Analysis of KEGG enrichment hinted that these 10 core genes were located in the pathways in cancer, suggesting that 1,4-naphthoquinone scaffold-derived compounds had potential activity against AML. Molecular docking analysis revealed that the binding energies between 1,4-naphthoquinone scaffold-derived compounds and the core proteins were all higher than - 6 kcal/mol, indicating that the 10 core targets all had strong binding ability with compounds. Moreover, a good binding capacity was inferred from molecular dynamics simulations between compound 7 and MMP9. The total binding free energy calculated using the MM/GBSA approach revealed values of - 6356.865 kcal/mol for the MMP9-7 complex. In addition, Bloodspot database results exhibited that HSP90AA1, MMP9 and PTPRC were associated with overall survival. The findings provide foundations for future studies into the interaction underlying the anti-AML potential of compounds with 1,4-naphthoquinone-based scaffold structures. Compounds with 1,4-naphthoquinone-based scaffold structures exhibits considerable potential in mitigating and treating AML through multiple targets and pathways.


Assuntos
Leucemia Mieloide Aguda , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Naftoquinonas , Mapas de Interação de Proteínas , Naftoquinonas/farmacologia , Naftoquinonas/química , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Farmacologia em Rede , Antineoplásicos/farmacologia , Antineoplásicos/química
4.
Heliyon ; 10(16): e36329, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39253110

RESUMO

Background: Progestin therapy is an option for patients with endometrial carcinoma (EC) or endometrial intraepithelial neoplasm (EIN) who fit specific criteria of fertility-sparing treatment. However, the implantation rate remains low among females receiving in vitro fertilization (IVF) even after the complete reversal of endometrial lesions. Methods: Here, ten patients with EC/EIN achieved complete regression (CR) in histology. Their relevant metabolic and IVF parameters were collected. An endometrial sampling at the window of implantation (WOI) and transcriptome analysis were conducted among them, and four healthy controls were analyzed to analyze endometrial receptivity. Results: On average, it took ten patients five months to achieve CR after four curettage procedures. The interquartile range of endometrium thickness on trigger day was between 8.8 and 10.0 mm, while the range was 15.2-18.5 mm for controls. Five patients got pregnant after a frozen-embryo transfer. According to ERA analysis, the endometrial sampling at WOI showed pre-receptive status in four cases. In total, 1458 differential expression genes were identified, and 70 belonged to the ERA genes. ImmuneScore indicated decreased NK cells in the endometrium, affecting endometrial receptivity. Conclusions: Even after EC/EIN reversal in histology, endometrial receptivity has already been compromised regarding altered WOI and immune microenvironment, leading to a low pregnancy rate.

5.
Protein Expr Purif ; : 106607, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260807

RESUMO

Plant non-specific lipid transfer protein (nsLTP) is able to bind and transport lipids and essential oils, as well as engage in various physiological processes, including defense against phytopathogens. Kalanchoe fedtschenkoi (Lavender Scallops) is an attractive and versatile succulent. To investigate the functional mechanism of Kalanchoe fedtschenkoi nsLTP (Ka-nsLTP), we expressed, purified and successfully obtained monomeric Ka-nsLTP. Mutational experiments revealed that the C6A variant retained the same activity as the wild-type (WT) Ka-nsLTP. Ka-nsLTP showed weak antiphytopathogenic bacterial activity, but inhibited fungal growth. Ka-nsLTP possessed a hydrophobic cavity effectively binding lauric acid. Our results offer novel molecular insights into the functional mechanism of nsLTP, which broadens our knowledge of the biological function of nsLTP in crops and provides a useful locus for genetic improvement of plants.

6.
Sci Total Environ ; : 176482, 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39317259

RESUMO

Debris flows are a prevalent mountain hazard that poses severe risks to human life and property. Debris-flow hazard assessments at the regional scale are vital for risk management, which establish spatial associations between debris flows and their influencing factors based on specific evaluation units. Different spatial scales of evaluation units can influence the spatial attributes and associations obtained by statistics, and further affect the accuracy of hazard assessments. However, there is limited consensus regarding the optimal spatial scale of evaluation units for debris-flow hazard assessment. To address this issue, six different scales of grid cells and forty influencing factors related to topography, material sources, hydrology, and human activities are analyzed by the geographical detector model to assess the debris-flow hazards in the Dadu River basin, China. The results reveal that over 92 % of debris-flow points fall within hazardous zones across all spatial scales, confirming the effectiveness of the assessment model. Topography, particularly local gully topography, dominates the debris-flow occurrence in the study area, while human activities also significantly contribute. As the spatial scale of evaluation units increases, the explanatory power of the influencing factors improves, with the 90 % quantile ranging from 0.23 to 0.46. This result suggests that larger spatial scales weaken the spatial characteristics of the factors. The finer and more informative the factors are, the more sensitive to spatial scale effects. The 10 km × 10 km is identified as the optimal spatial scale, which effectively preserves the local spatial characteristics while avoiding information loss or overload. These findings provide valuable insights for enhancing the accuracy of hazard assessments and improving the efficiency of risk management.

7.
Mol Plant ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39318094
8.
Brain Res Bull ; 217: 111077, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39265741

RESUMO

Neuropathic pain results from damage to nerves or the brain, and is characterized by symptoms such as allodynia, spontaneous pain, and hyperalgesia. The causes of this type of pain are intricate, which can make it difficult to treat. Sodium aescinate (SA), a natural extract from horse chestnut tree seeds, has been shown to act as a neuroprotector by inhibiting microglia activation. This study aims to explore the therapeutic potential of SA for neuropathic pain and the molecular mechanisms regulated by SA treatment. Through in vivo animal models and experiments, we found that SA treatment significantly reduced mechanical allodynia and heat hyperalgesia in neuropathic pain models. Additionally, SA inhibited O-GlcNAc-transferase (OGT)-induced O-GlcNAcylation (O-GlcNAc) modification in neuropathic pain mice. OGT overexpression could impede the therapeutic effects of SA on neuropathic pain. Further investigation revealed that Toll-like receptor 3 (TLR3), stabilized by OGT-induced O-GlcNAc modification, could activate the Mitogen activated protein kinase (MAPK) signaling pathway. Further in vivo experiments demonstrated that TLR3-mediated p38 mitogen-activated protein kinase (p38MAPK) activation is involved in SA-mediated relief of neuropathic pain. In conclusion, this study uncovers a novel molecular pathway deactivated by SA treatment in neuropathic pain.

9.
Medicine (Baltimore) ; 103(38): e39683, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312368

RESUMO

To explore the feasibility and application value of texture analysis based on computed tomography (CT) for predicting the differentiation of esophageal squamous cell carcinoma (ESCC). Patients diagnosed with ESCC who underwent chest contrast-enhanced CT before treatment were selected. Based on the pathological results, the patients were stratified into poorly differentiated and moderately well-differentiated groups. FireVoxel software was used to analyze the region of interest based on venous phase CT images. Texture parameters including the mean, median, standard deviation (SD), inhomogeneity, skewness, kurtosis, and entropy were obtained automatically. Differences in the texture parameters and their relationship with the degree of differentiation between the 2 groups were analyzed. The value of CT texture parameters in identifying poor differentiation and moderate-well differentiation of esophageal cancer was analyzed using the ROC curve. A total of 48 patients with ESCC were included, including 24 patients in the poorly differentiated group and 24 patients in the moderate-well-differentiated group. There were negative correlations between SD, inhomogeneity, entropy, and the degree of differentiation of esophageal cancer (P < .05). The correlation of inhomogeneity was the highest (r = -0.505, P < .001). SD, inhomogeneity, and entropy could effectively distinguish between the poorly and moderately well-differentiated groups, with statistically significant differences between the 2 groups (P < .05). The best critical values for SD, inhomogeneity, and entropy were 17.538, 0.017, and 3.917, respectively. The areas under the ROC curve were 0.793, 0.792, and 0.729, respectively, with the SD and inhomogeneity being the best. The application of texture analysis on venous phase CT images holds promise as a method for forecasting the degree of differentiation in esophageal cancers, which could significantly contribute to the preoperative noninvasive evaluation of tumor differentiation.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Tomografia Computadorizada por Raios X , Humanos , Masculino , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Idoso , Curva ROC , Diagnóstico Diferencial , Adulto , Estudos de Viabilidade , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos
11.
Epilepsy Behav ; 159: 110014, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39236374

RESUMO

PURPOSE: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE). METHODS: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE. RESULTS: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups. CONCLUSION: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe.


Assuntos
Circulação Cerebrovascular , Epilepsia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Feminino , Masculino , Adulto , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Epilepsia/complicações , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Adulto Jovem , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Qualidade do Sono , Idoso , Eletroencefalografia , Transtornos do Sono-Vigília/diagnóstico por imagem , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/etiologia
12.
Water Res ; 266: 122371, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39236500

RESUMO

Ambient operation and large-scale demonstration have limited the implementation and evaluation of anaerobic membrane bioreactors (AnMBRs) for low-strength wastewater treatment. Here, we studied these issues at an AnMBR demo plant that treats domestic wastewater and food waste together at ambient temperatures (7-28 °C). At varied hydraulic retention times (HRTs, 8-42 h), the AnMBR achieved a COD removal efficiency and biogas production of 80.4% ± 3.9% and 66.5 ± 9.4 NL/m3-Influent, respectively. Moreover, a stable high membrane flux of 14.4 L/m2/h was reached. The electric energy consumption for the AnMBR operation was 0.269-0.433 kW·h/m3, and 49.4%-91.3% could be compensated by the electric energy produced from methane production. At an HRT of 10 h, the AnMBR system demonstrated an impressively low net electric energy consumption of merely 0.05 kW·h/m3, resulting in a net greenhouse gas emission of 0.015 CO2-eq/m3, cutting 85% compared to the conventional activated sludge process. Achievements in this study provide key parameters for the ambient operation of AnMBR and demonstrate that AnMBR is an energy-saving and low-carbon solution for low-strength wastewater treatment.

13.
Int J Biol Macromol ; 279(Pt 4): 135455, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260653

RESUMO

(-)-ß-Elemene is a primary bioactive compound derived from Curcuma wenyujin and has been widely utilized as an anti-tumor agent for various types of cancer. Due to the inefficiency of plant extraction methods for ß-elemene, significant efforts have been directed toward the heterogeneous biosynthesis of ß-elemene using microbial cell factories. However, there has been less emphasis on the stereochemical configuration of germacrene A and its rearranged product, ß-elemene. In this study, we constructed a yeast cell factory to produce (-)-ß-elemene by optimizing the mevalonate pathway and screening for germacrene A synthases (GASs) from both plant and microbial sources. Notably, we discovered that the rearranged products of GASs exhibited different conformations, and only (+)-germacrene A produced by plant-derived GASs could rearrange to form (-)-ß-elemene. Building on this discovery, we further investigated the catalytic mechanisms of GASs and developed an efficient catalytic gene module for generating (+)-germacrene A. Ultimately, the engineered yeast produced 1152 mg/L of (-)-ß-elemene, marking the highest titer reported in yeast to date. Overall, this work highlights the differences in the stereoconformations of catalytic products between plant- and microbial-derived germacrene A synthases and establishes a foundation for the green and efficient production of ß-elemene with a specific stereochemical configuration.

14.
Int J Surg ; 110(9): 5496-5504, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39275772

RESUMO

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.


Assuntos
Procedimentos Cirúrgicos Eletivos , Ketamina , Complicações Pós-Operatórias , Humanos , Ketamina/administração & dosagem , Idoso , Feminino , Masculino , Método Duplo-Cego , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Anestesia Geral/efeitos adversos , Ritmo Circadiano , Delírio/prevenção & controle , Delírio/epidemiologia , Delírio/diagnóstico , Delírio do Despertar/prevenção & controle , Delírio do Despertar/epidemiologia , Delírio do Despertar/diagnóstico
15.
Int Immunopharmacol ; 142(Pt A): 113148, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39276449

RESUMO

Osteoarthritis (OA) is the most prevalent degenerative arthritis disease linked to aging, obesity, diet, and accumulation of octacalcium phosphate (OCP) crystals in joints. Current research has focused on inflammation and chondrocytes apoptosis as underlying OA mechanisms. Inflammatory cytokines like IL-1ß activate matrix metalloproteinase-13 (MMP-13) and aggrecanase (the member of A Disintegrin and Metalloproteinase with Thrombospondin motifs family, ADAMTS), leading to cartilage matrix degradation. The NLRP3 inflammasome also contributes to OA pathogenesis by maturing IL-1ß. Natural products like chondroitin sulfate oligosaccharides (oligo-CS) show promise in OA treatment by inhibiting inflammation. Our study evaluates the protective effects of oligo-CS against OA by targeting NLRP3 inflammation. Stimulating human SW1353 chondrocytes and human mononuclear macrophage THP-1 cells with OCP showed increased NLRP3 inflammation initiation, NF-κB pathway activation, and the production of inflammatory cytokines (IL-1ß, IL-6) and the metabolic index (MMP-13, ADAMTS-5), leading to cartilage matrix degradation. However, oligo-CS treatment significantly reduced inflammation. In a 28-day in vivo study with C57BL/6 female mice, OCP was injected into their right knee and oligo-CS was orally administered. The OCP group exhibited significant joint space narrowing and chondrocyte loss, while the oligo-CS group maintained cartilage integrity. Oligo-CS groups also regulated gut microbiota composition to a healthier state. Taken together, our findings suggest that oligo-CS can be considered as a protective compound against OA.

16.
Small ; : e2405748, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248683

RESUMO

Pt-based alloy with high mass activity and durability is highly desired for proton exchange membrane fuel cells, yet a great challenge remains due to the high mass transport resistance near catalysts with lowering Pt loading. Herein, an extensible approach employing atomic layer deposition to accurately introduce a gas-phase metal precursor into platinum nanoparticles (NPs) pre-filled mesoporous channels is reported, achieved by controlling both the deposition site and quantity. Following the spatially confined alloying treatment, the prepared PtSn alloy catalyst within mesopores demonstrates a small size and homogeneous distribution (2.10 ± 0.53 nm). The membrane electrode assembly with mesoporous carbon-supported PtSn alloy catalyst achieves a high initial mass activity of 0.85 A mg Pt - 1 ${\mathrm{mg}}_{\mathrm{Pt}}^{-1}$ at 0.9 V, which is attributed to the smallest local oxygen transport resistance (3.68 S m-1) ever reported. The mass activity of the catalyst only decreases by 11% after 30000 cycles of accelerated durability test, representing superior full-cell durability among the reported Pt-based alloy catalysts. The enhanced activity and durability are attributed to the decreased adsorption energy of oxygen intermediates on Pt surface and the strong electronic interaction between Pt and Sn inhibiting Pt dissolution.

17.
Vet Comp Oncol ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221701

RESUMO

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

18.
Bioorg Chem ; 151: 107697, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121594

RESUMO

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.


Assuntos
Imunoconjugados , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Estrutura Molecular , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/farmacologia , Anticorpos Monoclonais/química
19.
Environ Pollut ; 360: 124653, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39095002

RESUMO

Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 105, 5 × 105, and 1 × 106 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 µm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O2˙─) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate.


Assuntos
Antioxidantes , Cilióforos , Microplásticos , Cilióforos/fisiologia , Antioxidantes/metabolismo , Microplásticos/toxicidade , Poluentes Químicos da Água , Nanopartículas/toxicidade , Sulfetos/toxicidade
20.
Environ Pollut ; 360: 124649, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39095004

RESUMO

Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.


Assuntos
Bactérias , Poluentes Químicos da Água , Zooplâncton , Animais , Zooplâncton/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Microplásticos/toxicidade , Compostos de Enxofre , Sulfetos/toxicidade , Nanopartículas/toxicidade , Clorofila A/metabolismo , Plásticos
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