RÉSUMÉ
Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.
RÉSUMÉ
High basal autophagy and enhanced mitochondrial fission in triple-negative breast cancer (TNBC) cells support cell migration and promote plasticity of cancer cell metabolism. Here, we suggest a novel combination therapy approach for the treatment of TNBC that targets Drp1-mediated mitochondrial fission and autophagy pathways. Hydrogen sulfide (H2S) mediates a myriad of biological processes, including autophagy and mitochondrial function. In this study, we demonstrated that 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), one of the most widely utilized sustained-release H2S donors, effectively suppresses metastasis of TNBC cells in the absence of proliferation inhibition in vitro and in vivo. ADT-OH treatment ameliorated autophagy flux by suppressing autophagosome formation and induced mitochondrial elongation through decreasing expression of dynamin-related protein 1 (Drp1) and increasing expression of mitochondrial fusion protein (Mfn2). At the same time, ADT-OH downregulated mitophagy flux and inhibited mitochondrial function, eventually leading to the inhibition of migration and invasion in TNBC cells. In vivo, intraperitoneal administration of ADT-OH revealed a potent anti-metastatic activity in three different animal models, the MDA-MB-231 orthotopic xenograft model, the 4T1-Luci orthotopic model and the 4T1-Luci tail vein metastasis model. However, ADT-OH has an extremely low water solubility, which is a significant barrier to its effectiveness. Thus, we demonstrated that the solubility of ADT-OH in water can be improved significantly by absorption with hydroxypropyl-ß-cyclodextrin (CD). Remarkably, the obtained CD-ADT-OH demonstrated superior anti-cancer effect to ADT-OH in vivo. Altogether, this study describes a novel regulator of mammalian mitochondrial fission and autophagy, with potential utility as an experimental therapeutic agent for metastatic TNBC.
Sujet(s)
Autophagie , Dynamique mitochondriale , Tumeurs du sein triple-négatives , Tumeurs du sein triple-négatives/traitement médicamenteux , Tumeurs du sein triple-négatives/anatomopathologie , Tumeurs du sein triple-négatives/métabolisme , Dynamique mitochondriale/effets des médicaments et des substances chimiques , Humains , Animaux , Autophagie/effets des médicaments et des substances chimiques , Femelle , Lignée cellulaire tumorale , Souris , Mouvement cellulaire/effets des médicaments et des substances chimiques , Souris nude , Thiones/pharmacologie , Tests d'activité antitumorale sur modèle de xénogreffe , Souris de lignée BALB C , Mitochondries/métabolisme , Mitochondries/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Métastase tumorale , Sulfure d'hydrogène/pharmacologie , Sulfure d'hydrogène/métabolisme , Dynamines/métabolisme , Thiophènes/pharmacologieRÉSUMÉ
Protein homeostasis is essential for cyanobacteria to maintain proper cellular function under adverse and fluctuating conditions. The AAA+ superfamily of proteolytic complexes in cyanobacteria plays a critical role in this process, including ClpXP, which comprises a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. Despite the physiological effects of ClpX on growth and photosynthesis, its potential substrates and underlying mechanisms in cyanobacteria remain unknown. In this study, we employed a streptavidin-biotin affinity pull-down assay coupled with label-free proteome quantitation to analyze the interactome of ClpX in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis). We identified 503 proteins as potential ClpX-binding targets, many of which had novel interactions. These ClpX-binding targets were found to be involved in various biological processes, with particular enrichment in metabolic processes and photosynthesis. Using protein-protein docking, GST pull-down, and biolayer interferometry assays, we confirmed the direct association of ClpX with the photosynthetic proteins, ferredoxin-NADP+ oxidoreductase (FNR) and phycocyanin subunit (CpcA). Subsequent functional investigations revealed that ClpX participates in the maintenance of FNR homeostasis and functionality in Synechocystis grown under different light conditions. Overall, our study provides a comprehensive understanding of the extensive functions regulated by ClpX in cyanobacteria to maintain protein homeostasis and adapt to environmental challenges.
Sujet(s)
Photosynthèse , Synechocystis , Photosynthèse/génétique , Synechocystis/génétique , Synechocystis/métabolisme , Adenosine triphosphatases/génétique , Adenosine triphosphatases/métabolisme , Phycocyanine/métabolismeRÉSUMÉ
BACKGROUND: Ferroptosis, an iron-dependent process that regulates cell death. Emerging evidences suggest that ferroptosis induces acute kidney injury (AKI) progression, and inhibiting ferroptosis provides an effect strategy for AKI treatment. The disruption of the NRF2-KEAP1 protein to protein interaction (PPI) induces NRF2 activation, which provides a promising strategy that can identify new ferroptosis inhibitors. A previous study revealed that tiliroside, a glycosidic flavonoid extracted from Edgeworthia chrysantha Lindl (buds), has anti-neuroinflammatory and neuroprotective effects via NRF2 activation. However, the mechanism through which tiliroside activates NRF2 is unknown, and it remains unclear whether it has protective effects against AKI. PURPOSE: To investigate whether tiliroside has protective effects against AKI in mice and the associated mechanisms. METHODS: Possible tiliroside substrates were analyzed using molecular docking. Cisplatin- and ischemia-reperfusion injury (IRI)-induced AKI mouse models and HK2 cells model were constructed to evaluate the protective effects of tiliroside. CRISPR/Cas9 mediated NRF2 knockout HK2 cells were used to verify whether NRF2 mediates tiliroside protective effects. RESULTS: In vivo, our results showed that tiliroside treatment preserved kidney functions in AKI mice models, as showed by lower levels of serum creatinine (SCr), blood urea nitrogen (BUN), and renal injury markers, including neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1), compared with the mice in control groups. In vitro, tiliroside treatment greatly ameliorated cisplatin-induced ferroptosis through NRF2 activation in cultured HK2 cells, as evidenced by the protective effects of tiliroside being greatly blunted after the knockout of NRF2 in HK2 cells. Mechanistic studies indicated that tiliroside promoted NRF2/GPX4 pathway activation and ferroptosis inhibition, perhaps via the disruption of the NRF2-KEAP1 PPI. CONCLUSION: Together, our results demonstrate that tiliroside may serve as a NRF2-KEAP1 PPI inhibitor and prevents ferroptosis-induced AKI, indicating its potential for clinical AKI treatment.
Sujet(s)
Atteinte rénale aigüe , Ferroptose , Animaux , Souris , Protéine-1 de type kelch associée à ECH , Facteur-2 apparenté à NF-E2 , Cisplatine , Simulation de docking moléculaire , Atteinte rénale aigüe/traitement médicamenteux , Flavonoïdes/pharmacologieRÉSUMÉ
To increase the understanding of simple thin filamentous cyanobacteria in harsh environmental areas, we previously isolated and identified four strains (XN101, XN102, GS121, NX122) from desert soils and hot spring in China. As a result, two new Oculatellacean genera of these four strains, Gansulinema gen. nov. and Komarkovaeasiopsis gen. nov., are described based on a polyphasic approach. The ultrastructure of these strains showed a similar arrangement of peripheral thylakoids with three to four parallel layers, indicating that they belonged to the orders Nodosilineales, Oculatellales, or Leptolyngbyales. In the 16S rRNA gene phylogeny, two sequences of the Gansulinema strains and the two sequences of the Komarkovaeasiopsis strains formed two independent and robust clusters, within the order Oculatellales. The 16S rRNA gene sequences of strains of Komarkovaeasiopsis and Gansulinema showed low identity to each other (≤93.2%) and to other sequences of the Oculatellacean genera (≤94.5% and ≤93.3%, respectively). Furthermore, the 16S-23S internal transcribed spacer rRNA region secondary structures of strains of Komarkovaeasiopsis and Gansulinema were not consistent with all existing descriptions of Oculatellacean taxa. These data suggest that cyanobacterial communities are rich sources of new taxa in under-exploited areas, such as desert soils and hot spring in China.
Sujet(s)
Cyanobactéries , Sources thermales , ARN ribosomique 16S/génétique , Analyse de séquence d'ADN , ADN bactérien/génétique , Cyanobactéries/génétique , ARN ribosomique 23S/génétique , Phylogenèse , Acides grasRÉSUMÉ
Ferroptosis is iron-dependent and regulates necrosis caused by lipid peroxidation and mitochondrial damage. Recent evidence has revealed an emerging role for ferroptosis in the pathophysiology of acute kidney injury (AKI). Sulfide:quinone oxidoreductase (SQOR) is a mitochondrial inner membrane protein highly expressed in the renal cortex. However, the effects of SQOR on ferroptosis and AKI have not been elucidated. In this study, we evaluated the effects of SQOR in several AKI models. We observed a rapid decrease in SQOR expression after cisplatin stimulation in both in vivo and in vitro models. SQOR-deletion mice exhibit exacerbated kidney impairment and ferroptosis in renal tubular epithelial cells following cisplatin injury. Additionally, our results showed that the overexpression of SQOR or ADT-OH (the slow-releasing H2S donor) preserved renal function in the three AKI mouse models. These effects were evidenced by lower levels of serum creatinine (SCr), blood urea nitrogen (BUN), renal neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). Importantly, SQOR knockout significantly aggravates cisplatin-induced ferroptosis by promoting mitochondrial dysfunction in renal tubular epithelial cells (RTECs). Moreover, online database analysis combined with our study revealed that SYVN1, an upregulated E3 ubiquitin ligase, may mediate the ubiquitin-mediated degradation of SQOR in AKI. Consequently, our results suggest that SYVN1-mediated ubiquitination degradation of SQOR may induce mitochondrial dysfunction in RTECs, exacerbating ferroptosis and thereby promoting the occurrence and development of AKI. Hence, targeting the SYVN1-SQOR axis could be a potential therapeutic strategy for AKI treatment.
Sujet(s)
Atteinte rénale aigüe , Ferroptose , Maladies mitochondriales , Souris , Animaux , Cisplatine/effets indésirables , Atteinte rénale aigüe/étiologie , Oxidoreductases , Quinones , SulfuresRÉSUMÉ
BACKGROUND: Chronic kidney disease (CKD) involves a variety of pathological processes, and ferroptosis plays a vital role in CKD progression. Targeting ferroptosis is a promising strategy for the treatment of CKD. However, inhibitors of ferroptosis have not been used in the clinical treatment of CKD. Vitexin is a natural flavonoid with many biological activities and protective effects against various diseases. However, whether vitexin can prevent the progression of CKD is not known. METHODS: In vivo, the effect of vitexin on CKD was evaluated by using mouse models of unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion (UIR). Western blotting, Sirius red staining and transmission electron microscopy were used to analyze renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. In vitro, CCK8 assays and lipid peroxidation assays were performed to analyze cell viability and lipid peroxidation in human renal tubular epithelial cells (HK2 cells) induced by erastin. The activation of renal fibroblasts (NRK-49 F cells) was also analyzed. Additionally, an in-silico protein-drug docking model and coimmunoprecipitation were performed to determine the direct substrate of vitexin. RESULTS: In vivo, vitexin treatment significantly ameliorated renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. Additionally, our results showed that vitexin significantly attenuated UUO- and UIR-induced ferroptosis in renal tubular epithelial cells by upregulating glutathione peroxidase 4 (GPX4) protein levels and inhibiting lipid peroxidation in mouse kidneys. In vitro, treatment with vitexin inhibited erastin-induced ferroptosis in HK2 cells. Moreover, vitexin inhibited the expression of collagen I and α-SMA (alpha-smooth muscle actin) in NRK-49 F cells induced by the supernatant of erastin-treated HK2 cells. Mechanistically, our results suggested that vitexin could activate the NRF2/heme oxygenase-1 (HO-1) pathway by inhibiting the KEAP1- and ubiquitination-mediated degradation of NRF2, thereby increasing the expression of GPX4, and further inhibiting lipid peroxidation and ferroptosis. Additionally, knockout of NRF2 greatly inhibited the antiferroptotic effects of vitexin. CONCLUSIONS: Taken together, our results indicate that vitexin can protect against renal tubular epithelial cell ferroptosis in CKD by activating the KEAP1/NRF2/HO-1 pathway and is a promising drug to treat CKD.
Sujet(s)
Ferroptose , Insuffisance rénale chronique , Obstruction urétérale , Souris , Humains , Animaux , Facteur-2 apparenté à NF-E2/métabolisme , Protéine-1 de type kelch associée à ECH/métabolisme , Rein/métabolisme , Insuffisance rénale chronique/métabolisme , Obstruction urétérale/complications , Obstruction urétérale/traitement médicamenteux , Obstruction urétérale/métabolisme , Inflammation/métabolisme , Cellules épithéliales/métabolisme , FibroseRÉSUMÉ
BACKGROUND: Colorectal cancer is one of the most prevalent cancers in the world, but the research on its prevention, early diagnosis and treatment is still a major challenge in clinical oncology. Thus, there is a pressing requirement to find effective strategies to improve the survival of colon cancer patients. METHODS: Celecoxib has been accounted to be an effective antitumor drug, but may exhibit significant side effects. In recent studies, 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), one of the most commonly used reagents for the synthesis of sustained-release H2 S donors, has also been reported to inhibit cancer progression by affecting processes such as cell cycle, angiogenesis, and apoptosis. Therefore, we evaluated the therapeutic effect of the combination of ADT-OH and celecoxib on colorectal cancer through in vitro and in vivo, hoping to achieve better therapeutic effect and reduce the effect of celecoxib on gastric injury through exogenous administration of H2 S. RESULTS: Our results demonstrated that ADT-OH combined with celecoxib synergistically inhibited the proliferation and migration ability of human colorectal cancer HCT116 cells, altered cell cycle and cytoskeleton, increased intracellular reactive oxygen species (ROS), and promoted cell apoptosis. Noteworthy, in vivo studies also indicated the excellent antitumor therapeutic effect of the combination therapy without apparent toxicity. CONCLUSIONS: In general, our results provide a reasonable combination strategy of low-dose ADT-OH and celecoxib in the preclinical application of colorectal cancer.
Sujet(s)
Tumeurs du côlon , Thiones , Humains , Célécoxib/pharmacologie , Célécoxib/usage thérapeutique , Thiones/pharmacologie , Thiones/usage thérapeutique , Tumeurs du côlon/traitement médicamenteux , Apoptose , Prolifération cellulaire , Lignée cellulaire tumoraleRÉSUMÉ
Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Sujet(s)
Colite , Microbiome gastro-intestinal , Maladies inflammatoires intestinales , Humains , Souris , Animaux , , Souris de lignée C57BL , Colite/induit chimiquement , Colite/traitement médicamenteux , Colite/métabolisme , Maladies inflammatoires intestinales/traitement médicamenteux , Inflammation , Anti-inflammatoires/pharmacologie , Modèles animaux de maladie humaineRÉSUMÉ
Lipid droplet-associated proteins (LDAPs) play essential roles in tissue growth and development and in drought stress responses in plants. Cotton is an important fiber and cash crop; however, the LDAP family has not been characterized in cotton. In this study, a total of 14, six, seven, and seven genes were confirmed as LDAP family members in Gossypium hirsutum, Gossypium raimondii, Gossypium arboreum, and Gossypium stocksii, respectively. Additionally, expansion in the LDAP family occurred with the formation of Gossypium, which is mirrored in the number of LDAPs found in five Malvaceae species (Gossypioides kirkii, Bombax ceiba, Durio zibethinus, Theobroma cacao, and Corchorus capsularis), Arabidopsis thaliana, and Carica papaya. The phylogenetic tree showed that the LDAP genes in cotton can be divided into three groups (I, II, and III). The analysis of gene structure and conserved domains showed that LDAPs derived from group I (LDAP1/2/3) are highly conserved during evolution, while members from groups II and III had large variations in both domains and gene structures. The gene expression pattern analysis of LDAP genes showed that they are expressed not only in the reproductive organs (ovule) but also in vegetative organs (root, stem, and leaves). The expression level of two genes in group III, GhLDAP6_At/Dt, were significantly higher in fiber development than in other tissues, indicating that it may be an important regulator of cotton fiber development. In group III, GhLDAP2_At/Dt, especially GhLDAP2_Dt was strongly induced by various abiotic stresses. Decreasing the expression of GhLDAP2_Dt in cotton via virus-induced gene silencing increased the drought sensitivity, and the over-expression of GhLDAP2_Dt led to increased tolerance to mannitol-simulated osmotic stress at the germination stage. Thus, we conclude that GhLDAP2_Dt plays a positive role in drought tolerance.
RÉSUMÉ
KEY MESSAGE: We demonstrated a short-cycle B. napus line, Sef1, with a highly efficient and fast transformation system, which has great potential in large-scale functional gene analysis in a controlled environment. Rapeseed (Brassica napus L.) is an essential oil crop that accounts for a considerable share of global vegetable oil production. Nonetheless, studies on functional genes of B. napus are lagging behind due to the complicated genome and long growth cycle, this is largely due to the limited availability of gene analysis and modern genome editing-based molecular breeding. In this study, we demonstrated a short-cycle semi-winter-type Brassica napus 'Sef1' with very early-flowering and dwarf phenotype, which has great potential in large-scale indoor planting. Through the construction of an F2 population of Sef1 and Zhongshuang11, bulked segregant analysis (BSA) combined with the rape Bnapus50K SNP chip assay method was used to identify the early-flowering genes in Sef1, and a mutation in BnaFT.A02 was identified as a major locus significantly affecting the flowering time in Sef1. To further investigate the mechanism of early flowering in Sef1 and discover its potential in gene function analysis, an efficient Agrobacterium-mediated transformation system was established. The average transformation efficiency with explants of hypocotyls and cotyledons was 20.37% and 12.8%, respectively, and the entire transformation process took approximately 3 months from explant preparation to seed harvest of transformed plants. This study demonstrates the great potential of Sef1 for large-scale functional gene analysis.
Sujet(s)
Brassica napus , Brassica napus/génétique , Génomique , Phénotype , Séquençage par oligonucléotides en batterie , Environnement contrôléRÉSUMÉ
The B-BOX (BBX) gene family is widely distributed in animals and plants and is involved in the regulation of their growth and development. In plants, BBX genes play important roles in hormone signaling, biotic and abiotic stress, light-regulated photomorphogenesis, flowering, shade response, and pigment accumulation. However, there has been no systematic analysis of the BBX family in Platanus × acerifolia. In this study, we identified 39 BBX genes from the P. × acerifolia genome, and used TBtools, MEGA, MEME, NCBI CCD, PLANTCARE and other tools for gene collinearity analysis, phylogenetic analysis, gene structure, conserved domain analysis, and promoter cis-element analysis, and used the qRT-PCR and transcriptome data for analyzing expression pattern of the PaBBX genes. Collinearity analysis indicated segmental duplication was the main driver of the BBX family in P. × acerifolia, and phylogenetic analysis showed that the PaBBX family was divided into five subfamilies: I, II, III, IV and V. Gene structure analysis showed that some PaBBX genes contained super-long introns that may regulate their own expression. Moreover, the promoter of PaBBX genes contained a significant number of cis-acting elements that are associated with plant growth and development, as well as hormone and stress responses. The qRT-PCR results and transcriptome data indicated that certain PaBBX genes exhibited tissue-specific and stage-specific expression patterns, suggesting that these genes may have distinct regulatory roles in P. × acerifolia growth and development. In addition, some PaBBX genes were regularly expressed during the annual growth of P. × acerifolia, corresponding to different stages of flower transition, dormancy, and bud break, indicating that these genes may be involved in the regulation of flowering and/or dormancy of P. × acerifolia. This article provided new ideas for the study of dormancy regulation and annual growth patterns in perennial deciduous plants.
Sujet(s)
Protéines végétales , Facteurs de transcription , Protéines végétales/génétique , Protéines végétales/métabolisme , Phylogenèse , Facteurs de transcription/métabolisme , Génome végétal , Hormones , Régulation de l'expression des gènes végétauxRÉSUMÉ
Background: The aim of this study was to investigate the current state of disaster preparedness and to determine associated factors among emergency nurses from tertiary hospitals in Henan Province of China. Methods: This multicenter descriptive cross-sectional study was conducted with emergency nurses from 48 tertiary hospitals in Henan Province of China between September 7, 2022-September 27, 2022. Data were collected through a self-designeds online questionnaire using the mainland China version of the Disaster Preparedness Evaluation Tool (DPET-MC). Descriptive analysis and multiple linear regression analysis were used to evaluate disaster preparedness and to determine factors affecting disaster preparedness, respectively. Results: A total of 265 emergency nurses in this study displayed a moderate level of disaster preparedness with a mean item score of 4.24 out 6.0 on the DPET-MC questionnaire. Among the five dimensions of the DPET-MC, the mean item score for pre-disaster awareness was highest (5.17 ± 0.77), while that for disaster management (3.68 ± 1.36) was the lowest. Female gender (B = -9.638, p = 0.046) and married status (B = -8.618, p = 0.038) were negatively correlated with the levels of disaster preparedness. Five factors positively correlated with the levels of disaster preparedness included having attended in the theoretical knowledge training of disaster nursing since work (B = 8.937, p = 0.043), having experienced the disaster response (B = 8.280, p = 0.036), having participated in the disaster rescue simulation exercise (B = 8.929, p = 0.039), having participated in the disaster relief training (B = 11.515, p = 0.025), as well as having participated in the training of disaster nursing specialist nurse (B = 16.101, p = 0.002). The explanatory power of these factors was 26.5%. Conclusion: Emergency nurses in Henan Province of China need more education in all areas of disaster preparedness, especially disaster management, which needs to be incorporated into nursing education, including formal and ongoing education. Besides, blended learning approach with simulation-based training and disaster nursing specialist nurse training should be considered as novel ways to improve disaster preparedness for emergency nurses in mainland China.
Sujet(s)
Protection civile , Catastrophes , Infirmières et infirmiers , Humains , Femelle , Études transversales , Centres de soins tertiaires , ChineRÉSUMÉ
Although imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), s develop resistance to imatinib when progress to blast phase and relapse. Myricetin, a flavonoid compound found in natural plants, has multiple biological functions. In this study, we show that myricetin demonstrated potent efficacy in imatinib-resistant CML CD34 + stem/progenitor cells with less toxicity in normal bone marrow. Myricetin is also active against imatinib-resistant CML bulk cells. The in vitro observations on the therapeutic effects of myricetin were translatable to in vivo imatinib-resistant CML xenograft mouse models. Mechanism studies showed that myricetin decreased the phosphorylation of eIF4E and Ak strain transforming, and the protein level of c-Myc and Cyclin D1. Rescue studies using eIF4E (S209D) and (S209A) confirmed that eIF4E phosphorylation inhibition was the mechanism of myricetin's action in CML. Our results suggest that myricetin may be a potential lead for drug development to overcome imatinib resistance in CML.
Sujet(s)
Facteur-4E d'initiation eucaryote , Leucémie myéloïde chronique BCR-ABL positive , Humains , Animaux , Souris , Mésilate d'imatinib/pharmacologie , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Flavonoïdes/pharmacologie , Résistance aux médicaments antinéoplasiques , ApoptoseRÉSUMÉ
As the global climate problem becomes increasingly serious, the green technology innovation to achieve "carbon peak and carbon neutral" has gradually become the global consensus of major countries, and how the rapid development of artificial intelligence (AI) technology affects green technology innovation (GTI) has received a great deal of attention in the field of economics. Therefore, based on China's inter-provincial panel data from 2006 to 2019, the system GMM, dynamic panel threshold model, and quantile regression model were constructed to examine various influences of AI development on GTI under different environmental regulation intensity, research and development (R&D) investment, and institutional environmental threshold conditions. The findings presented that AI development significantly contributes to GTI and GTFP, with an impact coefficient of 0.0122 and 0.0084, and this influence is mainly reflected in the western region of China and is more obvious in the 2006-2012 period. AI development mainly enhances green technological efficiency, and it has dampening effects on green technological progress during the period 2013-2019. Additionally, there are non-linear threshold effects in the relationship between the level of AI development and GTI when environmental regulatory intensity, R&D investment, and institutional environment are in different level intervals. AI development will boost GTI only when the intensity of environmental regulation and institutional environment is above a certain threshold value. However, the AI development represented by industrial robot applications still has no obvious effect on GTI even when the R&D investment exceeds a certain threshold. Furthermore, the growth effect of AI development on GTI indicates a decreasing nonlinear pattern as the GTI's quantile rises under the condition that R&D investment and institutional environment intensity cross the threshold, while this growth effect increases gradually with the rise of GTI's quantile when the environmental regulation is above the threshold.
Sujet(s)
Intelligence artificielle , Inventions , Technologie , Développement économique , Chine , CarboneRÉSUMÉ
FADD, a classical apoptotic signaling adaptor, has recently been reported to exhibit a series of non-apoptotic functions. Here, we report that FADD may play a critical role in the development of renal fibrosis. Neutrophil infiltration in the renal interstitial part, glomerular mesangial cell proliferation, and base-membrane thickening were observed in FADD-D mice by H&E, PAS, and PASM staining. Immunofluorescence analysis revealed that macrophage infiltration was significantly enhanced in FADD-D mice. Renal fibrosis might be induced by IgA nephritis in FADD-D mice as evidenced by increased Ki67 and type IV collagen. Additionally, the levels of α-SMA, Fibronectin, and Vimentin were also found to be elevated. Mechanism study indicated that the TLR4/myD88/NF-κB signaling pathway was activated in FADD-D mice. Moreover, FADD phosphorylation activated the mTOR and TGF-ß/Smad pathway and accelerated the process of epithelial mesenchymal transition. Further studies indicated that the TGF-ß1 pathway was also activated and the process of EMT was accelerated in both FADD-disrupted HEK293 cells and FADD-deficient MES cells. Thus, we concluded that FADD phosphorylation could lead to IgA nephritis and eventually result in renal fibrosis. Taken together, our study provides evidence, for the first time, that FADD, especially in its phosphorylated form, has an effect on the development of renal fibrosis.Abbreviations: FADD: FAS-associated protein with death domain; DED: death effector domain; DD: death domain; CKD: chronic kidney disease; ECM: extracellular matrix; ESRD: end-stage renal disease; RRT: renal replacement therapy; H&E: hematoxylin and eosin; PASM: periodic acid silver methenamine.
Sujet(s)
Maladies du rein , Néphrite , Souris , Humains , Animaux , Transition épithélio-mésenchymateuse , Phosphorylation , Cellules HEK293 , Maladies du rein/métabolisme , Facteur de croissance transformant bêta-1/métabolisme , Fibrose , Immunoglobuline A/métabolisme , Protéine à domaine de mort associée à Fas/métabolisme , Protéine à domaine de mort associée à Fas/pharmacologieRÉSUMÉ
Background and aims: Hypercholesterolemia has been identified as risk factor for severe acute pancreatitis (AP). We aimed to identify the common differentially expressed genes (DEGs) between a high-cholesterol diet and AP. Methods: We retrived gene expression profiles from the GEO database. DEGs were assessed using GEO2R. For AP hub genes, we conducted functional enrichment analysis and protein-protein interaction (PPI) analysis. GeneMANIA and correlation analysis were employed to predict potential DEG mechanisms. Validation was done across various healthy human tissues, pancreatic adenocarcinoma, peripheral blood in AP patients, and Sprague-Dawley rats with AP. Results: The gene "Fabp5" emerged as the sole common DEG shared by a high-cholesterol diet and AP. Using the 12 topological analysis methods in PPI network analysis, Rela, Actb, Cdh1, and Vcl were identified as hub DEGs. GeneMANIA revealed 77.6% physical interactions among Fabp5, TLR4, and Rela, while genetic correlation analysis indicated moderate associations among them. Peripheral blood analysis yielded area under the ROC curve (AUC) values of 0.71, 0.63, 0.74, 0.64, and 0.91 for Fabp5, TLR4, Actb, Cdh1 genes, and artificial neural network (ANN) model respectively, in predicting severe AP. In vivo immunohistochemical analysis demonstrated higher Fabp5 expression in the hyperlipidemia-associated AP group compared to the AP and control groups. Conclusion: Fabp5 emerged as the common DEG connecting a high-cholesterol diet and AP. Rela was highlighted as a crucial hub gene in AP. Genetic interactions were observed among Fabp5, TLR4, and Rela. An ANN model consisting of Fabp5, TLR4, Actb, and Cdh1 was helpful in predicting severe AP.
RÉSUMÉ
Background: Sleep disorders are prevalent among patients with schizophrenia and are associated with several negative consequences. Although, researchers have recently suggested that sleep disorders have a close correlation with alexithymia, and schizophrenia also has a strong correlation with alexithymia, there have been few studies on the relationships between schizophrenia, sleep disorders and alexithymia. Therefore, this study aimed to explore the relationships between psychiatric symptoms, alexithymia and sleep problems in patients with schizophrenia so as to provide a reference for the clinical treatment of this comorbidity. Methods: In total, 977 patients with schizophrenia were recruited for this study. The Insomnia Severity Index (ISI) was used to assess sleep disorders, and the Positive and Negative Syndrome Scale (PANSS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Toronto Alexithymia Scale (TAS) were used to evaluate clinical symptoms, cognitive functions and the ability to express emotion, respectively. Results: The results indicated that the PANSS subscales (G-subscore) and TAS group were risk factors for insomnia in schizophrenia patients (all p < 0.05). The mediation model showed the standardized path coefficients from schizophrenia to alexithymia (ß = 0.104, p < 0.001) and from alexithymia to insomnia (ß = 0.038, p < 0.001) were statistically significant. Conclusion: The results of this study indicated that alexithymia is associated with sleep disturbance in patients with schizophrenia. These findings may provide a new avenue for the treatment of schizophrenia patients with sleep disorders.