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1.
Inflammation ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963571

ABSTRACT

Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1ß, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1ß, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.

2.
Cell Biol Toxicol ; 40(1): 52, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967699

ABSTRACT

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.


Subject(s)
Extracellular Vesicles , Glial Fibrillary Acidic Protein , Mesenchymal Stem Cells , MicroRNAs , Osteoclasts , Osteoporosis , Rats, Sprague-Dawley , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Mesenchymal Stem Cells/metabolism , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Osteoporosis/metabolism , Osteoporosis/genetics , Glial Fibrillary Acidic Protein/metabolism , Glial Fibrillary Acidic Protein/genetics , Rats , Osteoclasts/metabolism , Male , Cell Differentiation , Magnetite Nanoparticles , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/genetics , Diabetes Complications/metabolism , Diabetes Complications/genetics
3.
J Biomed Mater Res A ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949056

ABSTRACT

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

4.
Geriatr Nurs ; 58: 472-479, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955038

ABSTRACT

AIM: This study aimed to investigate factors affecting physical activity (PA) among elderly stroke survivors living in the community and assess the mediating role of exercise planning in the relationship between exercise self-efficacy and PA. METHODS: 300 participants were surveyed using questionnaires and scales, with data analyzed using SPSS 26.0. RESULTS: Univariate analysis identified sociological, disease-related factors, exercise self-efficacy, and exercise planning as influencing PA. Ordered logistic regression showed significant associations between PA, exercise self-efficacy (OR 1.093, 95 % CI 1.055-1.133, P < 0.001), and exercise planning (OR 1.296, 95 % CI 1.202-1.398, P < 0.001). Exercise planning partially mediated the relationship between exercise self-efficacy and PA, accounting for 64.86 % of the total effect. CONCLUSIONS: Multiple factors, including sociological and disease-related ones, as well as exercise self-efficacy and planning, influence PA in elderly stroke survivors. Exercise planning partially mediates the relationship between exercise self-efficacy and PA.

5.
Front Endocrinol (Lausanne) ; 15: 1405283, 2024.
Article in English | MEDLINE | ID: mdl-38938514

ABSTRACT

Background: A common sense is that lower serum cholesterol levels are better. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over. Methods: We selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey(CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome was all-cause mortality. The univariate and multivariate Cox regression analyses were used to estimate risk levels of all-cause mortality. We stratified the participants into three groups (<3.40, 3.40-4.39, ≥4.39 mmol/L) based on the restricted cubic splines methods. The survival probability according to total cholesterol category was calculated using the Kaplan-Meier curves, and the log-rank test was performed to analyze differences between the groups. Results: During the follow-up of three years, 282 participants died, 497 survived and 124 lost to follow-up. There was significant relationship between the total cholesterol and lower risk of all-cause mortality in the multivariable Cox regression analysis (HR=0.88, 95% CI: 0.78-1.00). Based on the restricted cubic splines methods, the total cholesterol was converted from a continuous variable to a categorical variable. The populations were divided into three groups (<3.40, 3.40-4.39, ≥4.39 mmol/L) according to the total cholesterol categorized by cutoff values. Compared to the total cholesterol level of <3.40 mmol/L, populations in the total cholesterol level of 3.40-4.39 mmol/L (HR = 0.72, 95% CI: 0.53-0.97) and ≥4.39 mmol/L (HR = 0.71, 95% CI: 0.52-0.96) groups had lower all-cause mortality in multivariate Cox regression analysis and higher survival probability in survival analysis. When two groups were divided, similar results were found among the populations in the total cholesterol level of ≥3.40 mmol/L compared to the populations in the total cholesterol level of <3.40 mmol/L groups. Conclusion: In oldest old aged 85 and older, serum total cholesterol levels are inversely associated with all-cause mortality. This study suggested that total cholesterol should be maintained to acceptable levels (≥ 3.40 mmol/L) in oldest old to achieve longevity.


Subject(s)
Cholesterol , Mortality , Humans , Cholesterol/blood , Female , Longitudinal Studies , Male , Aged, 80 and over , Mortality/trends , China/epidemiology , Cause of Death , Longevity , Risk Factors , Follow-Up Studies
6.
Fundam Res ; 4(1): 103-112, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38933835

ABSTRACT

Oceanic uptake and storage of anthropogenic CO2 (CANT) are regulated by ocean circulation and ventilation. To decipher the storage and redistribution of CANT in the western North Pacific, where a major CANT sink develops, we investigated the water column carbonate system, dissolved inorganic radiocarbon and ancillary parameters in May and August 2018, spanning the Kuroshio Extension (KE, 35-39 °N), Kuroshio Recirculation (KR, 27-35 °N) and subtropical (21-27 °N) zones. Water column CANT inventories were estimated to be 40.5 ± 1.1 mol m-2 in the KR zone and 37.2 ± 0.9 mol m-2 in the subtropical zone. In comparison with historical data obtained in 2005, relatively high rates of increase of the CANT inventory of 1.05 ± 0.20 and 1.03 ± 0.12 mol m-2 yr-1 in the recent decade were obtained in the KR and subtropical zones, respectively. Our water-mass-based analyses suggest that formation and transport of subtropical mode water dominate the deep penetration, storage, and redistribution of CANT in those two regions. In the KE zone, however, both the water column CANT inventory and the decadal CANT accumulation rate were small and uncertain owing to the dynamic hydrology, where the naturally uplifting isopycnal surfaces make CANT penetration relatively shallow. The findings of this study improve the understanding of the spatiotemporal variations of CANT distribution, storage, and transport in the western North Pacific.

7.
Entropy (Basel) ; 26(6)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38920520

ABSTRACT

Adopting biomass energy as an alternative to fossil fuels for electricity production presents a viable strategy to address the prevailing energy deficits and environmental concerns, although it faces challenges related to suboptimal energy efficiency levels. This study introduces a novel combined cooling and power (CCP) system, incorporating an externally fired gas turbine (EFGT), steam Rankine cycle (SRC), absorption refrigeration cycle (ARC), and organic Rankine cycle (ORC), aimed at boosting the efficiency of biomass integrated gasification combined cycle systems. Through the development of mathematical models, this research evaluates the system's performance from both thermodynamic and exergoeconomic perspectives. Results show that the system could achieve the thermal efficiency, exergy efficiency, and levelized cost of exergy (LCOE) of 70.67%, 39.13%, and 11.67 USD/GJ, respectively. The analysis identifies the combustion chamber of the EFGT as the component with the highest rate of exergy destruction. Further analysis on parameters indicates that improvements in thermodynamic performance are achievable with increased air compressor pressure ratio and gas turbine inlet temperature, or reduced pinch point temperature difference, while the LCOE can be minimized through adjustments in these parameters. Optimized operation conditions demonstrate a potential 5.7% reduction in LCOE at the expense of a 2.5% decrease in exergy efficiency when compared to the baseline scenario.

8.
Article in English | MEDLINE | ID: mdl-38878896

ABSTRACT

OBJECTIVE: The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae. METHODS: Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model. RESULTS: A 2-4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56. CONCLUSION: The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

9.
Pestic Biochem Physiol ; 202: 105959, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879341

ABSTRACT

ε-Poly-l-lysine (ε-PL) is an effective antimicrobial peptide for controlling fungal plant diseases, exhibiting significant antifungal activity and safety. Despite its known efficacy, the potential of ε-PL in combating plant bacterial diseases remains underexplored. This study evaluated the effectiveness of ε-PL and its nanomaterial derivative in managing tomato bacterial spot disease caused by Pseudomonas syringae pv. tomato. Results indicated that ε-PL substantially inhibited the growth of Pseudomonas syringae pv. tomato. Additionally, when ε-PL was loaded onto attapulgite (encoded as ATT@PL), its antibacterial effect was significantly enhanced. Notably, the antibacterial efficiency of ATT@PL containing 18.80 µg/mL ε-PL was even close to that of 100 µg/mL pure ε-PL. Further molecular study results showed that, ATT@PL stimulated the antioxidant system and the salicylic acid signaling pathway in tomatoes, bolstering the plants disease resistance. Importantly, the nanocomposite demonstrated no negative effects on both seed germination and plant growth, indicating its safety and aligning with sustainable agricultural practices. This study not only confirmed the effectiveness of ε-PL in controlling tomato bacterial spot disease, but also introduced an innovative high antibacterial efficiency ε-PL composite with good bio-safety. This strategy we believe can also be used in improving other bio-pesticides, and has high applicability in agriculture practice.


Subject(s)
Anti-Bacterial Agents , Plant Diseases , Polylysine , Pseudomonas syringae , Silicon Compounds , Solanum lycopersicum , Pseudomonas syringae/drug effects , Solanum lycopersicum/microbiology , Polylysine/pharmacology , Polylysine/chemistry , Anti-Bacterial Agents/pharmacology , Plant Diseases/microbiology , Plant Diseases/prevention & control , Silicon Compounds/pharmacology , Silicon Compounds/chemistry , Magnesium Compounds
10.
Small ; : e2402206, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38881367

ABSTRACT

The challenges of sodium metal anodes, including formation of an unstable solid-electrolyte interphase (SEI) and uncontrolled growth of sodium dendrites during charge-discharge cycles, impact the stability and safety of sodium metal batteries. Motivated by the promising commercialization potential of sodium metal batteries, it becomes imperative to systematically explore innovative protective interlayers specifically tailored for sodium metal anodes. In this work, a NaBix/NaVyOz hybrid and porous interfacial layer on sodium anode is successfully fabricated via pretreating sodium with bismuth vanadate. The hybrid interlayer effectively combines the advantages of sodium vanadates and alloys, raising a synergistic effect in facilitating sodium deposition kinetics and inhibiting the growth of sodium dendrites. As a result, the modified sodium electrodes (BVO-Na) can stably cycle for 2000 h at 0.5 mA cm-2 with a fixed capacity of 1 mAh cm-2, and the BVO-Na||Na3V2(PO4)3 full cell sustains a high capacity of 94 mAh g-1 after 600 cycles at 5 C. This work demonstrates that constructing an artificial hybrid interlayer is a practical solution to obtain high performance anodes in sodium metal batteries.

11.
Nat Commun ; 15(1): 5107, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877001

ABSTRACT

Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.


Subject(s)
14-3-3 Proteins , Arabidopsis Proteins , Arabidopsis , Phytic Acid , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Phytic Acid/metabolism , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Phosphorylation , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Mutation , Cell Membrane/metabolism , Gene Expression Regulation, Plant , Inositol Phosphates/metabolism
12.
Bioconjug Chem ; 35(6): 758-765, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38857526

ABSTRACT

Bacterial keratitis, an ocular emergency, is the predominant cause of infectious keratitis. However, diagnostic procedures for it are invasive, time-consuming, and expeditious, thereby limiting effective treatment for the disease in the clinic. It is imperative to develop a timely and convenient method for the noninvasive diagnosis of bacterial keratitis. Fluorescence imaging is a convenient and noninvasive diagnostic method with high sensitivity. In this study, a type of nitroreductase-responsive probe (NTRP), which responds to nitroreductase to generate fluorescence signals, was developed as an activatable fluorescent probe for the imaging diagnosis of bacterial keratitis. Imaging experiments both in vitro and in vivo demonstrated that the probe exhibited "turn-on" fluorescence signals in response to nitroreductase-secreting bacteria within 10 min. Furthermore, the fluorescence intensity reached its highest at 4 or 6 h in vitro and at 30 min in vivo when the excitation wavelength was set at 520 nm. Therefore, the NTRP has the potential to serve as a feasible agent for the rapid and noninvasive in situ fluorescence diagnosis of bacterial keratitis.


Subject(s)
Fluorescent Dyes , Keratitis , Nitroreductases , Fluorescent Dyes/chemistry , Nitroreductases/metabolism , Nitroreductases/analysis , Keratitis/diagnosis , Keratitis/microbiology , Animals , Humans , Optical Imaging/methods , Mice
13.
Appl Opt ; 63(16): 4284-4292, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38856604

ABSTRACT

The development of modern large-scale spectroscopic survey telescopes responds to the urgent demand for spectral information in astronomical research. Tsinghua University has previously proposed a 6.5 m MUltiplexed Survey Telescope consisting of a Ritchey-Chretien configuration and a 1.8 m multi-element wide-field corrector, achieving excellent performance and world-leading survey efficiency. However, an optimized 1.65 m multi-element corrector with five lenses is proposed to overcome the constraints on glass uniformity and verification in fabrication of the previous corrector design. It maintains outstanding image quality, with the 80% enclosed energy diameter not more than 0.559 arcsec within 3° FoV over up to a 55° zenith angle. The optimized optical system does not revise the working mode of the ADC or the curvature of the primary mirror while ensuring the reasonability and accuracy of manufacturing of large corrector elements. It provides a more feasible reference optical design for the MUltiplexed Survey Telescope in subsequent iterations and communications with manufacturers.

14.
Eur J Gastroenterol Hepatol ; 36(7): 815-830, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829940

ABSTRACT

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.


Subject(s)
Acupuncture Therapy , Constipation , Dietary Fiber , Fecal Microbiota Transplantation , Probiotics , Constipation/therapy , Constipation/microbiology , Humans , Fecal Microbiota Transplantation/adverse effects , Dietary Fiber/therapeutic use , Probiotics/therapeutic use , Probiotics/adverse effects , Chronic Disease , Acupuncture Therapy/methods , Treatment Outcome , Network Meta-Analysis , Randomized Controlled Trials as Topic , Quality of Life , Laxatives/therapeutic use
15.
Sci Rep ; 14(1): 13244, 2024 06 09.
Article in English | MEDLINE | ID: mdl-38853158

ABSTRACT

Aiming at the problem of image classification with insignificant morphological structural features, strong target correlation, and low signal-to-noise ratio, combined with prior feature knowledge embedding, a deep learning method based on ResNet and Radial Basis Probabilistic Neural Network (RBPNN) is proposed model. Taking ResNet50 as a visual modeling network, it uses feature pyramid and self-attention mechanism to extract appearance and semantic features of images at multiple scales, and associate and enhance local and global features. Taking into account the diversity of category features, channel cosine similarity attention and dynamic C-means clustering algorithms are used to select representative sample features in different category of sample subsets to implicitly express prior category feature knowledge, and use them as the kernel centers of radial basis probability neurons (RBPN) to realize the embedding of diverse prior feature knowledge. In the RBPNN pattern aggregation layer, the outputs of RBPN are selectively summed according to the category of the kernel center, that is, the subcategory features are combined into category features, and finally the image classification is implemented based on Softmax. The functional module of the proposed method is designed specifically for image characteristics, which can highlight the significance of local and structural features of the image, form a non-convex decision-making area, and reduce the requirements for the completeness of the sample set. Applying the proposed method to medical image classification, experiments were conducted based on the brain tumor MRI image classification public dataset and the actual cardiac ultrasound image dataset, and the accuracy rate reached 85.82% and 83.92% respectively. Compared with the three mainstream image classification models, the performance indicators of this method have been significantly improved.


Subject(s)
Deep Learning , Neural Networks, Computer , Humans , Algorithms , Image Processing, Computer-Assisted/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/classification , Brain Neoplasms/pathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods
16.
Heliyon ; 10(11): e31865, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845899

ABSTRACT

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of ß2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of ß2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-ß2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between ß2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-ß2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting ß2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

18.
Cancer Res ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861363

ABSTRACT

Colorectal cancer (CRC) is the second most common malignant tumor world-wide. Analysis of the changes that occur during CRC progression could provide insights into the molecular mechanisms driving CRC development and identify improved treatment strategies. Here, we performed an integrated multi-omics analysis of 435 trace-tumor-samples from 148 colorectal cancer (CRC) patients, covering non-tumor (NT), intraepithelial neoplasia (IEN), infiltration (IFT), and advanced-stage CRC (A-CRC) phases. Proteogenomics analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidation phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, occurred predominantly in the IEN and IFT phases, respectively, and impacted the cell cycle. Mutation of TP53 was frequent in the A-CRC phase and associated with tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of CRC based on CMS and CRIS classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of CRC based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided CRC. The AOM/DSS-induced CRC carcinogenesis mouse model in mice indicated that DDX5 deletion due to chr17q loss promoted CRC development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of CRC and identifying the potential therapeutic targets.

19.
Mol Plant ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38902921

ABSTRACT

Xenia, the phenomenon in which the pollen genotype directly affects the phenotypic characteristics of the maternal tissues (i.e., fruit ripening), has applications in crop production and breeding. However, the underlying molecular mechanism has yet to be elucidated. Here, we investigated whether mobile mRNAs from the pollen affect the ripening and quality-related characteristics of the fruit using cross-pollination between distinct Malus domestica (apple) cultivars. We demonstrated that hundreds of mobile mRNAs originating from the seeds are delivered to the fruit. We also found that the movement of one of these mRNAs, ACC oxidase 3 (MdACO3), is coordinated with fruit ripening. Salicylic acid treatment, which can cause plasmodesmal closure, blocks MdACO3 movement, indicating that MdACO3 transcripts may move through plasmodesmata. To assess the role of mobile MdACO3 transcripts in apple fruit, we created MdACO3-GFP-expressing apple seeds using MdACO3-GFP-overexpressing pollen for pollination and showed that MdACO3 transcripts in the transgenic seeds move to the flesh where they regulate fruit ripening. Furthermore, we demonstrated that MdACO3 can be transported from the seeds to fruit in the fleshy-fruited species tomato and strawberry. These results underscore the potential of mobile mRNAs from seeds to influence fruit characteristics, providing an explanation for the xenia phenomenon. Notably, our findings highlight the feasibility of leveraging diverse pollen genomic resources, without resorting to genome editing, to improve fruit quality.

20.
Plant Physiol Biochem ; 212: 108783, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824694

ABSTRACT

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 µmol m-2·s-1; T2, 3R: 1B, 279.69 µmol m-2·s-1; T3, 7R: 1B, 211.16 µmol m-2·s-1). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment.


Subject(s)
Chlorophyll , Cimicifuga , Light , Photosynthesis , Chlorophyll/metabolism , Cimicifuga/metabolism , Seedlings/growth & development , Seedlings/metabolism , Carotenoids/metabolism , Plant Leaves/metabolism , Plant Leaves/growth & development , Chlorophyll A/metabolism
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