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1.
Angew Chem Int Ed Engl ; : e202410743, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963024

ABSTRACT

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

2.
Front Vet Sci ; 11: 1388532, 2024.
Article in English | MEDLINE | ID: mdl-38988981

ABSTRACT

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn't impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

3.
Front Psychol ; 15: 1331425, 2024.
Article in English | MEDLINE | ID: mdl-38873500

ABSTRACT

Background: Occupational commitment (OC) is a multidimensional construct that predicts turnover intentions. The interindividual variability of nurses' OC merits further exploration. Therefore, this study aims to examine patterns of OC and its relationship with psychological empowerment and job crafting in nurses. Methods: A sample of 1,061 nurses was recruited from February 2022 to April 2022 by using a stratified four-stage cluster sampling procedure. A self-report survey included the Psychological Empowerment Scale, Job Crafting Scale, and Occupational Commitment Scale. Latent profile analysis (LPA) was used to examine the patterns of OC. Associations of the latent class membership with individual characteristics, psychological empowerment and job crafting were examined using multinomial logistic regression. Results: Three patterns of OC were identified: (1) "Low OC group" (n = 224, 21.1%); (2) "Moderate OC group" (n = 665, 62.7%); (3) "High OC group" (n = 172, 16.2%). Nurses with higher education, fewer years of service, working in medicine, lower psychological empowerment and lower job crafting had a higher likelihood of belonging to Class 1 (Low OC group). In contrast, nurses working in emergency and with higher psychological empowerment and job crafting were more likely to belong to Class 3 (High OC group). Conclusion: The findings revealed the heterogeneity of occupational commitment among nurses in China and could guide the identification and early intervention of nurses with low level of occupational commitment.

4.
Org Lett ; 26(26): 5528-5533, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38901007

ABSTRACT

This paper outlines an innovative three-component coupling strategy for the 1,4-difunctionalization of 1,3-butadiene, utilizing sodium decatungstate (NaDT) as a hydrogen atom transfer (HAT) photocatalyst. The photoinduced process efficiently generates homoallylic amino acid esters with 100% atom economy, employing readily available components under mild reaction conditions. This light-induced protocol eliminates the need for an additional transition metal catalysts, additives, or equivalent reducing agents. The study explored various C(sp3)-H bearing partners, butadienes, and α-iminoesters, demonstrating the versatility and synthetic utility of this method.

5.
Aquat Toxicol ; 272: 106967, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38833998

ABSTRACT

Microplastics (MPs) are ubiquitous in aquatic environments, which can act as carriers to affect the bioavailability of heavy metals. The aging process in the environment changes the physicochemical properties of MPs, thereby affecting their environmental behavior and co-toxicity with other pollutants. However, relevant research is limited. In this study, we compared the properties and Cu2+ adsorption capacity of pristine and aged polytetrafluoroethylene (PTFE) MPs and further explored the influence on copper bioavailability and bio-effects on Microcystis aeruginosa. Aging process induced surface oxidation and cracks of PTFE MPs, and decreased the stability of MPs in water by increasing zeta potential. PTFE MPs had a strong adsorption capacity for Cu2+ and increased the bioavailability of copper to microalgae, which was not affected by the aging process. Pristine and aged PTFE MPs adhered to cyanobacterium surfaces and caused shrinkage and deformation of cells. Inhibition of cyanobacterium growth, photosynthesis and reduction of total antioxidant capacity were observed in the treatment of PTFE MPs. Combined exposure of pristine MPs and Cu2+ had stronger toxic effects to cyanobacterium, and increased Microcystin-LR release, which could cause harm to aquatic environment. Aging reduced the toxic effects of PTFE MPs on microalgae. Furthermore, soluble exopolysaccharide (EPS) content was significantly higher in co-exposure of aged MPs and Cu2+, which could reduce the toxicity to cyanobacterium cells. These results indicate that aging process alleviates the toxicity to microalgae and environmental risks caused by PTFE MPs. This study improves understanding of the combined toxicity of aged MPs and metals in freshwater ecosystems.


Subject(s)
Biological Availability , Copper , Microcystis , Microplastics , Polytetrafluoroethylene , Water Pollutants, Chemical , Microcystis/drug effects , Copper/toxicity , Water Pollutants, Chemical/toxicity , Microplastics/toxicity , Polytetrafluoroethylene/chemistry , Polytetrafluoroethylene/toxicity , Ultraviolet Rays , Adsorption , Microalgae/drug effects
7.
Heliyon ; 10(9): e30131, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707430

ABSTRACT

Utilizing city-level data from China, the paper employs a spatial econometric analysis to investigate the impact of fiscal decentralization on urban pollution. Empirical evidence indicates: (1) In the context of the emphasis of ecological civilization construction in China, an increase of fiscal autonomy for local governments is conducive to mitigating urban pollution intensity. Specifically, fiscal decentralization in one city not only promotes a reduction in local pollution intensity but alleviates environmental pollution problems in adjacent cities through spatial spillover effects. (2) Industrial structure upgrading and green technology progress become crucial measures for local governments to realize pollution reduction targets through fiscal expenditure. (3) Heterogeneity analysis reveals that the positive significance of decentralization is most prominent in the eastern China, while local governments with fiscal autonomy in central region tend to transfer pollution to neighboring cities. (4) There is a threshold characteristic for fiscal decentralization to promote a reduction in urban pollution intensity, and its marginal effect becomes more significant accompanied by continuous introduction of sophisticated foreign direct investment. Finally, the paper summarizes the potential significance of fiscal decentralization among Chinese local governments against the background of "Chinese-style decentralization" and proposes corresponding policy recommendations.

8.
J Biomed Res ; : 1-15, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38807380

ABSTRACT

Given the extremely high inter-patient heterogeneity among acute myeloid leukemia (AML), identifying biomarkers for prognostic assessment and therapeutic guidance is crucial. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In this study, we evaluate the prognostic potential of all human CSMs in AML patients based on differential gene expression analysis and univariate Cox regression analysis. Utilizing multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we construct a 9-CSMs prognostic model for risk stratification of AML patients. The predictive value of the 9-CSMs risk score is further confirmed in three independent datasets. Multivariate Cox regression analysis shows that the risk score is an independent prognostic factor for AML patients. AML patients with high 9-CSMs risk scores have shorter overall and event-free survival time than those with lower scores. Notably, our single-cell RNA-seq analysis indicates that patients with high 9-CSMs risk scores exhibit chemotherapy resistance. Further, PI3K inhibitors are identified as potential treatments for these high-risk patients. In conclusion, we construct a 9-CSMs prognostic model which is an independent prognostic factor for the survival of AML patients and has the potential to guide drug therapy.

9.
Food Res Int ; 187: 114345, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763637

ABSTRACT

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.


Subject(s)
Chenopodium quinoa , Diet, Western , Fermentation , Gastrointestinal Microbiome , Hordeum , Lactobacillus , Rats, Sprague-Dawley , Animals , Hordeum/chemistry , Male , Lactobacillus/metabolism , Chenopodium quinoa/chemistry , Rats , Liver/metabolism , Dysbiosis , Metabolomics , Fermented Foods , Multiomics
10.
J Am Chem Soc ; 146(17): 12053-12062, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38622809

ABSTRACT

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

11.
Front Psychol ; 15: 1308863, 2024.
Article in English | MEDLINE | ID: mdl-38659680

ABSTRACT

Introduction: The mental health of university students is influenced by a variety of factors, including self-esteem and personality traits, with resilience playing a crucial role in mediating and moderating these relationships. This study investigates the intricate dynamics affecting mental well-being in Chinese university students, focusing on the roles of self-esteem, personality traits, and the interventional effects of resilience. Methods: A cross-sectional survey was conducted with 689 students, aged on average 20.3 years, between April and July 2022. The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) was used to assess mental well-being, while resilience, personality traits, and self-esteem were evaluated using the revised Connor-Davidson Resilience Scale (CD-RISC), the Chinese version of the Big Five Inventory-2 (BFI-2), and the Texas Social Behavior Inventory (TSBI), respectively. Results: Analysis revealed significant correlations between self-esteem, personality traits, and both resilience and mental well-being. Resilience was found to partially mediate the relationship between self-esteem and mental well-being and fully mediate certain aspects of the relationship between personality traits and mental well-being. Additionally, tenacity and autonomy were identified as moderators in the link between specific personality traits and mental well-being. Discussion: The findings highlight the complex interplay between self-esteem, personality traits, resilience, and mental well-being, underscoring the critical role of resilience. This insight is pivotal for developing targeted interventions to bolster mental well-being among university students, emphasizing the need for multifaceted support strategies to enhance student mental health.

12.
Heliyon ; 10(5): e27417, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38486755

ABSTRACT

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

13.
Clin Epigenetics ; 16(1): 48, 2024 03 26.
Article in English | MEDLINE | ID: mdl-38528641

ABSTRACT

BACKGROUND: miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. METHODS: To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. RESULTS: miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. CONCLUSIONS: Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.


Subject(s)
Antineoplastic Agents , MicroRNAs , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Adult , Animals , Humans , Mice , Antineoplastic Agents/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , DNA Methylation/genetics , Lymphocytes/metabolism , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Sulfonamides/therapeutic use , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism
14.
Commun Biol ; 7(1): 280, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38448784

ABSTRACT

X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.


Subject(s)
Research , Tomography, X-Ray Computed , X-Rays , Radiography , Optical Imaging
15.
J Phys Chem A ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38477590

ABSTRACT

Zero-dimensional kinetic modeling of atmospheric pressure Ar-N2-H2 nonthermal plasma was carried out to gain mechanistic insights into plasma-assisted catalytic synthesis of ammonia. Ar dilution is a common technique for tailoring plasma discharge properties and has been shown to enhance NH3 formation when added to N2-H2 plasma. The kinetic model was developed for a coaxial dielectric barrier discharge quartz wool-packed bed reactor operating at near room temperature using a kHz-frequency plasma source. With 30% Ar mixed in a 1:1 N2-H2 plasma at 760 Torr, we find that NH3 production is dominated by Eley-Rideal (E-R) surface reactions, which heavily involve surface NHx species derived from N and H radicals in the gas phase, while the influence of excited N2 molecules is negligible. This is contrary to the commonly proposed mechanism that excited N2 molecules created by Penning excitation of N2 by Ar(4s) and Ar(4p) play a significant role in assisting NH3 formation. Our model shows that the enhanced NH3 formation upon Ar dilution is unlikely due to the interactions between Ar and H species, as excited Ar atoms have a weak effect on H radical formation through H2 dissociation compared to electrons. We find that excited Ar atoms contribute to 28% of the N radical production in the gas phase via N2 dissociation, while the rest are dominated by electron-impact dissociation. Furthermore, Ar species play a negligible role in the product NH3 dissociation. N2 conversion sensitivity analyses were carried out for electron number density (ne) and reduced electric field (E/N), and contributions from Ar to gas-phase N radical production were quantified. The model can provide guidance on potential reasons for observing enhanced NH3 formation upon Ar dilution in N2-H2 plasma beyond changes in the discharge characteristics.

16.
Microorganisms ; 12(2)2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38399655

ABSTRACT

Clubroot (Plasmodiophora brassicae) is an important soilborne disease that causes severe damage to cruciferous crops in China. This study aims to compare the differences in chemical properties and microbiomes between healthy and clubroot-diseased soils. To reveal the difference, we measured soil chemical properties and microbial communities by sequencing 18S and 16S rRNA amplicons. The available potassium in the diseased soils was higher than in the healthy soils. The fungal diversity in the healthy soils was significantly higher than in the diseased soils. Ascomycota and Proteobacteria were the most dominant fungal phylum and bacteria phylum in all soil samples, respectively. Plant-beneficial microorganisms, such as Chaetomium and Sphingomonas, were more abundant in the healthy soils than in the diseased soils. Co-occurrence network analysis found that the healthy soil networks were more complex and stable than the diseased soils. The link number, network density, and clustering coefficient of the healthy soil networks were higher than those of the diseased soil networks. Our results indicate that the microbial community diversity and network structure of the clubroot-diseased soils were different from those of the healthy soils. This study is of great significance in exploring the biological control strategies of clubroot disease.

17.
Exp Hematol Oncol ; 13(1): 19, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378601

ABSTRACT

BACKGROUND: Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. METHODS: Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. RESULTS: We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. CONCLUSIONS: Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

18.
J Assist Reprod Genet ; 41(3): 591-608, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38315418

ABSTRACT

Precise extravillous trophoblast (EVT) invasion is crucial for successful placentation and pregnancy. This review focuses on elucidating the mechanisms that promote heightened EVT invasion. We comprehensively summarize the pivotal roles of hormones, angiogenesis, hypoxia, stress, the extracellular matrix microenvironment, epithelial-to-mesenchymal transition (EMT), immunity, inflammation, programmed cell death, epigenetic modifications, and microbiota in facilitating EVT invasion. The molecular mechanisms underlying enhanced EVT invasion may provide valuable insights into potential pathogenic mechanisms associated with diseases characterized by excessive invasion, such as the placenta accreta spectrum (PAS), thereby offering novel perspectives for managing pregnancy complications related to deficient EVT invasion.


Subject(s)
Extravillous Trophoblasts , Trophoblasts , Pregnancy , Female , Humans , Trophoblasts/metabolism , Placentation/physiology , Epithelial Cells , Placenta/metabolism
19.
Int J Biol Macromol ; 264(Pt 1): 130323, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38387628

ABSTRACT

Clubroot, caused by the obligate parasite Plasmodiophora brassicae, is one of the most important diseases of brassicas. The antagonistic bacterium Paenibacillus polymyxa ZF129 can suppress clubroot while its effectiveness is often unstable. To control clubroot more effectively, the macrobeads for controlled release of ZF129 were prepared using microencapsulation technology. Macrobeads with various ratios of chitosan (2 % w/w): carrageenan (0.3 % w/v) were prepared by an ionotropic gelation method and the bacteria ZF129 was loaded into macrobeads. The 1:1 chitosan: carrageenan showed the maximum swelling ratio (634 %), and the maximum survival rate (61.52 ± 1.12 %) after freeze-drying. Fourier transform infrared revealed the electrostatic interactions between chitosan and carrageenan. The macrobeads can efficiently release ZF129 strains into phosphate buffer solution and reach equilibrium in 48 h. The maximum number of bacteria cells to be released in the soil was observed after 25-30 days. The control efficacy of ZF129 macrobeads (chitosan: carrageenan, 1:1) and ZF129 culture against clubroot disease was 76.33 ± 3.65 % and 59.76 ± 4.43 % in greenhouse experiments, respectively and the control efficacy was calculated as 60.74 ± 5.00 % for ZF129 macrobeads and 40.94 ± 4.05 % for ZF129 culture under field experiments, respectively. The ZF129 macrobeads had significant growth-promoting effects on pak choi and Chinese cabbage. The encapsulation method described in this study is a prudent approach toward efficient biopesticides utilization with reduced environmental implications.


Subject(s)
Brassica , Chitosan , Paenibacillus polymyxa , Carrageenan , Crops, Agricultural
20.
Environ Sci Pollut Res Int ; 31(6): 9062-9077, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38182959

ABSTRACT

Based on the panel data of 259 cities across China from 2011 to 2019, the study investigates the long-run impact of digital economy on regional pollution intensity by employing multiple models. The estimation results reveal that (1) the relatively heavily polluted areas are concentrated in the north, especially in the northeast of China; the overall pollution intensity is decreasing year by year at the national level; (2) the development of digital economy can significantly contribute to the reduction of regional pollution intensity and it has a statistically significant negative spatial spillover effect on the pollution intensity of neighboring cities; (3) mechanism analysis shows that the development of digital economy not only has a direct effect on the reduction of pollution intensity but also promotes the reduction through the channel of industrial structure upgrading and green technology progress; (4) the results of threshold model suggest that as the level of development of the digital economy increases, its marginal inhibitory effect of promoting the decrease in pollution intensity will diminish; (5) heterogeneity analysis shows that the development of digital economy makes the strongest marginal contribution to pollution intensity reduction in the northeast region. Finally, the conclusions remain valid after controlling for exogenous shocks such as "smart city" policy, various robustness, and endogeneity tests.


Subject(s)
Environmental Pollution , Industry , China , Cities , Policy , Economic Development
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