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1.
Synth Syst Biotechnol ; 10(1): 39-48, 2025.
Article in English | MEDLINE | ID: mdl-39224148

ABSTRACT

Bacillus licheniformis is a significant industrial microorganism. Traditional gene editing techniques relying on homologous recombination often exhibit low efficiency due to their reliance on resistance genes. Additionally, the established CRISPR gene editing technology, utilizing Cas9 endonuclease, faces challenges in achieving simultaneous knockout of multiple genes. To address this limitation, the CRISPR-Cpf1 system has been developed, enabling multiplexed gene editing across various microorganisms. Key to the efficient gene editing capability of this system is the rigorous screening of highly effective expression elements to achieve conditional expression of protein Cpf1. In this study, we employed mCherry as a reporter gene and harnessed P mal for regulating the expression of Cpf1 to establish the CRISPR-Cpf1 gene editing system in Bacillus licheniformis. Our system achieved a 100 % knockout efficiency for the single gene vpr and up to 80 % for simultaneous knockout of the double genes epr and mpr. Furthermore, the culture of a series of protease-deficient strains revealed that the protease encoded by aprE contributed significantly to extracellular enzyme activity (approximately 80 %), whereas proteases encoded by vpr, epr, and mpr genes contributed to a smaller proportion of extracellular enzyme activity. These findings provide support for effective molecular modification and metabolic regulation in industrial organisms.

2.
Article in English | MEDLINE | ID: mdl-39225219

ABSTRACT

OBJECTIVE: Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS. METHODS: We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot. RESULTS: The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway. CONCLUSION: The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.

3.
Microbiol Res ; 289: 127881, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39241502

ABSTRACT

Mannitol, one of the most widespread sugar alcohols, has been integral to daily human life for two centuries. Global population growth and competition for freshwater, food, and land have prompted a shift in the fermentation industry from terrestrial to marine raw materials. Mannitol is a readily available carbohydrate in brown seaweed from the ocean and possess a higher reducing power than glucose, making it a promising substrate for biological manufacturing. This has spurred numerous explorations into converting mannitol into high-value chemicals. Researchers have engineered microorganisms to utilize mannitol in various synthetic biological applications, including: (1) employing mannitol as an inducer to control the activation and deactivation of genetic circuits; (2) using mannitol as a carbon source for synthesizing high-value chemicals through biomanufacturing. This review summarizes the latest advances in the application of mannitol in synthetic biology. AIM OF REVIEW: The aim is to present a thorough and in-depth knowledge of mannitol, a marine carbon source, and then use this carbon source in synthetic biology to improve the competitiveness of biosynthetic processes. We outlined the methods and difficulties of utilizing mannitol in synthetic biology with a variety of microbes serving as hosts. Furthermore, future research directions that could alleviate the carbon catabolite repression (CCR) relationship between glucose and mannitol are also covered. EXPECTED CONTRIBUTIONS OF REVIEW: Provide an overview of the current state, drawbacks, and directions for future study on mannitol as a carbon source or genetic circuit inducer in synthetic biology.

4.
Breast Cancer Res ; 26(1): 129, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232806

ABSTRACT

BACKGROUND: The internal heterogeneity of breast cancer, notably the tumor microenvironment (TME) consisting of malignant and non-malignant cells, has been extensively explored in recent years. The cells in this complex cellular ecosystem activate or suppress tumor immunity through phenotypic changes, secretion of metabolites and cell-cell communication networks. Macrophages, as the most abundant immune cells within the TME, are recruited by malignant cells and undergo phenotypic remodeling. Tumor-associated macrophages (TAMs) exhibit a variety of subtypes and functions, playing significant roles in impacting tumor immunity. However, their precise subtype delineation and specific function remain inadequately defined. METHODS: The publicly available single-cell transcriptomes of 49,141 cells from eight breast cancer patients with different molecular subtypes and stages were incorporated into our study. Unsupervised clustering and manual cell annotation were employed to accurately classify TAM subtypes. We then conducted functional analysis and constructed a developmental trajectory for TAM subtypes. Subsequently, the roles of TAM subtypes in cell-cell communication networks within the TME were explored using endothelial cells (ECs) and T cells as key nodes. Finally, analyses were repeated in another independent publish scRNA datasets to validate our findings for TAM characterization. RESULTS: TAMs are accurately classified into 7 subtypes, displaying anti-tumor or pro-tumor roles. For the first time, we identified a new TAM subtype capable of proliferation and expansion in breast cancer-TUBA1B+ TAMs playing a crucial role in TAMs diversity and tumor progression. The developmental trajectory illustrates how TAMs are remodeled within the TME and undergo phenotypic and functional changes, with TUBA1B+ TAMs at the initial point. Notably, the predominant TAM subtypes varied across different molecular subtypes and stages of breast cancer. Additionally, our research on cell-cell communication networks shows that TAMs exert effects by directly modulating intrinsic immunity, indirectly regulating adaptive immunity through T cells, as well as influencing tumor angiogenesis and lymphangiogenesis through ECs. CONCLUSIONS: Our study establishes a precise single-cell atlas of breast cancer TAMs, shedding light on their multifaceted roles in tumor biology and providing resources for targeting TAMs in breast cancer immunotherapy.


Subject(s)
Breast Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Tumor-Associated Macrophages , Humans , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Female , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Cell Communication/immunology , Biomarkers, Tumor/genetics , Endothelial Cells/metabolism , Endothelial Cells/pathology
5.
Front Microbiol ; 15: 1412502, 2024.
Article in English | MEDLINE | ID: mdl-39247700

ABSTRACT

Objective: Pulmonary artery hypertension (PAH) poses a significant challenge due to its limited therapeutic options and high mortality rates. The ACE2-Ang-(1-7)-Mas axis plays a pivotal role in regulating blood pressure and inhibiting myocardial remodeling. However, the precise mechanistic links between the ACE2-Ang-(1-7)-Mas axis and PAH remain poorly understood. This study aimed to elucidate the involvement of the ACE2-Ang-(1-7)-Mas axis in the development of PAH. Methods: PAH was induced in mice using Sugen5416/hypoxia, PAAT/PET ratio and PA were detected using cardiac ultrasound; inflammation related factors such as MCP-1, TNF, IL-10and IL-12p70 were detected in intestines using cytometric bead array (CBA) kits; histopathological and morphological changes in lung and intestinal tissues were assessed via HE staining and Masson staining to evaluate the progression of PAH. Immunohistochemistry and western blotting were employed to determine the expression levels of two tight junction proteins, occludin and ZO-1, in intestinal tissues. Additionally, 16rRNA sequencing and non-targeted metabolomics by LC-MS/MS techniques were utilized to investigate the impact of the ACE2-Ang-(1-7)-Mas axis on microbial diversity and metabolomics of intestinal contents. Results: Activation of the ACE2-Ang-(1-7)-Mas axis improves heart function, reduces intestines inflammatory factors and ameliorates pathological and histological alterations in SuHx mice. This activation notably upregulated the expression of occludin and ZO-1 proteins in intestinal tissues and promoted the proliferation of SCFA-producing bacteria genera, such as g_Candidatus_Saccharimonas. Furthermore, it enhanced the abundance of beneficial metabolites, including tryptophan and butyric acid. Conclusion: The findings suggest that modulation of the ACE2-Ang-(1-7)-Mas axis can alleviate PAH by regulating intestinal microbes and metabolites. These results highlight the potential of the ACE2-Ang-(1-7)-Mas axis as a promising therapeutic target for clinical management of PAH.

6.
J Neurointerv Surg ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39209427

ABSTRACT

BACKGROUND: Cerebral arteriovenous malformation (AVM) is a cerebrovascular disorder posing a risk for intracranial hemorrhage. However, there are few reliable quantitative indices to predict hemorrhage risk accurately. This study aimed to identify potential biomarkers for hemorrhage risk by quantitatively analyzing the hemodynamic and morphological features within the AVM nidus. METHODS: This study included three datasets comprising consecutive patients with untreated AVMs between January 2008 to December 2023. Training and test datasets were used to train and evaluate the model. An independent validation dataset of patients receiving conservative treatment was used to evaluate the model performance in predicting subsequent hemorrhage during follow-up. Hemodynamic and morphological features were quantitatively extracted based on digital subtraction angiography (DSA). Individual models using various machine learning algorithms and an ensemble model were constructed on the training dataset. Model performance was assessed using the confusion matrix-related metrics. RESULTS: This study included 844 patients with AVMs, distributed across the training (n=597), test (n=149), and validation (n=98) datasets. Five hemodynamic and 14 morphological features were quantitatively extracted for each patient. The ensemble model, constructed based on five individual machine-learning models, achieved an area under the curve of 0.880 (0.824-0.937) on the test dataset and 0.864 (0.769-0.959) on the independent validation dataset. CONCLUSION: Quantitative hemodynamic and morphological features extracted from DSA data serve as potential indicators for assessing the rupture risk of AVM. The ensemble model effectively integrated multidimensional features, demonstrating favorable performance in predicting subsequent rupture of AVM.

7.
Microorganisms ; 12(8)2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39203534

ABSTRACT

Bacillus licheniformis is recognised as an exceptional expression platform in biomanufacturing due to its ability to produce high-value products. Consequently, metabolic engineering of B. licheniformis is increasingly pursued to enhance its utility as a biomanufacturing vehicle. Effective B. licheniformis cell factories require promoters that enable regulated expression of target genes. This review discusses recent advancements in the characterisation, synthesis, and engineering of B. licheniformis promoters. We highlight the application of constitutive promoters, quorum sensing promoters, and inducible promoters in protein and chemical synthesis. Additionally, we summarise efforts to expand the promoter toolbox through hybrid promoter engineering, transcription factor-based inducible promoter engineering, and ribosome binding site (RBS) engineering.

8.
Sci Rep ; 14(1): 20018, 2024 08 28.
Article in English | MEDLINE | ID: mdl-39198599

ABSTRACT

Deep learning techniques were used in ophthalmology to develop artificial intelligence (AI) models for predicting the short-term effectiveness of anti-VEGF therapy in patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME). 180 BRVO-ME patients underwent pre-treatment FFA scans. After 3 months of ranibizumab injections, CMT measurements were taken at baseline and 1-month intervals. Patients were categorized into good and poor prognosis groups based on macular edema at the 4th month follow-up. FFA-Net, a VGG-based classification network, was trained using FFA images from both groups. Class activation heat maps highlighted important locations. Benchmark models (DesNet-201, MobileNet-V3, ResNet-152, MansNet-75) were compared for training results. Performance metrics included accuracy, sensitivity, specificity, F1 score, and ROC curves. FFA-Net predicted BRVO-ME treatment effect with an accuracy of 88.63% and an F1 score of 0.89, with a sensitivity and specificity of 79.40% and 71.34%, respectively.The AUC of the ROC curve for the FFA-Net model was 0.71. The use of FFA based on deep learning technology has feasibility in predicting the treatment effect of BRVO-ME. The FFA-Net model constructed with the VGG model as the main body has good results in predicting the treatment effect of BRVO-ME. The typing of BRVO in FFA may be an important factor affecting the prognosis.


Subject(s)
Fluorescein Angiography , Neural Networks, Computer , Ranibizumab , Retinal Vein Occlusion , Humans , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/diagnostic imaging , Retinal Vein Occlusion/complications , Male , Female , Treatment Outcome , Fluorescein Angiography/methods , Ranibizumab/therapeutic use , Ranibizumab/administration & dosage , Middle Aged , Aged , Macular Edema/drug therapy , Macular Edema/diagnostic imaging , Macular Edema/etiology , Deep Learning , Angiogenesis Inhibitors/therapeutic use , Prognosis , ROC Curve
9.
Clin Neurol Neurosurg ; 245: 108515, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39178636

ABSTRACT

BACKGROUND: Cognard type IIa+b dural arteriovenous fistulas (DAVFs) in the lateral sinuses are often complicated with venous sinus obstruction and accompanied by clinical symptoms and a risk of hemorrhage. The purpose of this study was to assess venous sinus stenting as a viable alternative treatment in complex lateral sinus DAVFs and examine its efficacy and safety. METHODS: We retrospectively examined patients diagnosed with type IIa+b DAVF in the transverse or sigmoid sinus with associated venous sinus occlusion who were treated via stent placement between April 2017 and June 2019. RESULTS: Six patients were included in this study. Three patients had DAVFs in both the transverse and sigmoid sinuses, two in the transverse sinus and confluence of sinuses, and one in the transverse sinus. The most common symptoms were headache, dizziness, and limb weakness. At the last follow-up, three patients had significant improvement, and three were asymptomatic. Angiograms performed immediately after the surgery showed restoration of the anterograde venous drainage in all patients. According to the follow-up angiography results, two DAVFs were completely obliterated, and four remained as stable type I DAVFs. Most patients had satisfactory venous sinus drainage, except one who had in-stent stenosis. CONCLUSIONS: Stent placement can restore sinus patency, improve clinical symptoms, and decrease intracranial hemorrhage risk. This approach may be an effective option for treating type IIa+b lateral DAVFs complicated by sinus occlusion.


Subject(s)
Central Nervous System Vascular Malformations , Cranial Sinuses , Stents , Humans , Male , Middle Aged , Female , Central Nervous System Vascular Malformations/complications , Central Nervous System Vascular Malformations/surgery , Central Nervous System Vascular Malformations/diagnostic imaging , Aged , Retrospective Studies , Cranial Sinuses/surgery , Cranial Sinuses/diagnostic imaging , Adult , Treatment Outcome , Transverse Sinuses/surgery , Plastic Surgery Procedures/methods , Endovascular Procedures/methods
10.
Article in English | MEDLINE | ID: mdl-39135387

ABSTRACT

Aims: Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. Results: The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. Innovation and Conclusion: In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity.

11.
Am J Transl Res ; 16(7): 2921-2930, 2024.
Article in English | MEDLINE | ID: mdl-39114671

ABSTRACT

BACKGROUND: Prostate cancer poses a significant risk to men's health. In this study, a model for differentiating benign and malignant nodules in the central region of the prostate was constructed by combining multi-parametric MRI and hematological lab values. METHODS: This retrospective study analyzed the data acquired from Lianyungang First People's Hospital and The Second Affiliated Hospital of Hainan Medical College from January 2018 to December 2021. We included 310 MRI-confirmed prostatic nodule patients. The data were split into a training set (260 cases) and an external validation set (50 cases), with the latter exclusively from The Second Affiliated Hospital of Hainan Medical College to test the model's generalizability. Univariate and multivariate logistic regression identified critical measurements for differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH), which were then integrated into a nomogram model. RESULTS: The key indicators determined by multivariate logistic regression analysis included apparent diffusion coefficient (ADC), standard deviation (StDev), neutrophil to lymphocyte ratio (NLR), and prostate specific antigen (PSA). The nomogram's performance, as indicated by the area under the curve (AUC), was 0.844 (95% CI: 0.811-0.938) in the training set and 0.818 (95% CI: 0.644-0.980) in the external validation set. Calibration and decision curves demonstrated that the nomogram was well-calibrated and could serve as an effective tool in clinical practice. CONCLUSION: The nomogram model based on ADC, StDev, NLR and PSA may be helpful to identify PCa and BPH.

12.
Heliyon ; 10(15): e35406, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39170288

ABSTRACT

Background: This study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. Methods: The 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. Findings: Visual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. Interpretation: Treatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

13.
Imeta ; 3(4): e215, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39135688

ABSTRACT

BioLadder (https://www.bioladder.cn/) is an online data analysis platform designed for proteomics research, which includes three classes of experimental data analysis modules and four classes of common data analysis modules. It allows for a variety of proteomics analyses to be conducted easily and efficiently. Additionally, most modules can also be utilized for the analysis of other omics data. To facilitate user experience, we have carefully designed four different kinds of functions for customers to quickly and accurately utilize the relevant analysis modules.

14.
Antioxidants (Basel) ; 13(7)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-39061877

ABSTRACT

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation, affecting physiological and pathological processes. Fatty liver disease associated with metabolic dysfunction is a common pathological condition in aquaculture. However, the exact role and mechanism of ferroptosis in its pathogenesis and progression remains unclear. In this study, an experiment was conducted using different dietary lipid levels in the feeding of largemouth bass (Micropterus salmoides) for 11 weeks. The results revealed that the growth performance and whole-body protein content significantly increased with the elevation of dietary lipid levels up to 12%. The activities of antioxidant enzymes as well as the content of GSH (glutathione) in the liver initially increased but later declined as the lipid levels increased; the contents of MDA (malondialdehyde) and GSSG (oxidized glutathione) demonstrated an opposite trend. Moreover, elevating lipid levels in the diet significantly increased liver Fe2+ content, as well as the expressions of TF (Transferrin), TFR (Transferrin receptor), ACSL4 (acyl-CoA synthetase long-chain family member 4), LPCAT3 (lysophosphatidylcholine acyltransferase 3), and LOX12 (Lipoxygenase-12), while decreasing the expressions of GPX4 (glutathione peroxidase 4) and SLC7A11 (Solute carrier family 7 member 11). In conclusion, the optimal lipid level is 12.2%, determined by WG-based linear regression. Excess lipid-level diets can up-regulate the ACSL4/LPCAT3/LOX12 axis, induce hepatic oxidative stress and cell death through a ferroptotic-like program, and decrease growth performance.

15.
Research (Wash D C) ; 7: 0407, 2024.
Article in English | MEDLINE | ID: mdl-38979515

ABSTRACT

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through ß1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

17.
Cell Prolif ; : e13700, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38924190

ABSTRACT

Tamoxifen resistance is a common and difficult problem in the clinical treatment of breast cancer (BC). As a novel antitumor agent, Micheliolide (MCL) has shown a better therapeutic effect on tumours; however, little is known about MCL and its role in BC therapy. With tamoxifen stimulation, drug-resistant BC cells MCF7TAMR and T47DTAMR obtained a high oxidative status and Amidohydrolase 1 (ASAH1) was abnormally activated. The inhibition of ASAH1 rescued the sensitivity of resistant cells to tamoxifen. We found that MCL inhibited the expression of ASAH1 and cell proliferation, especially in MCF7TAMR and T47DTAMR cells. The high oxidative stress status of resistant cells stimulated the expression of ASAH1 by positively regulating AKT, which was restrained by MCL. MCL activated NRF2 by directly binding to KEAP1 and promoting the antioxidant level of tamoxifen-resistant (TAMR) cells. In addition, ACT001, the prodrug of MCL, significantly inhibited the tumour growth of TAMR cells in preclinical xenograft tumour models. In conclusion, ASAH1 mediates tamoxifen resistance in ER-positive BC cells. MCL could activate the cellular antioxidant system via NRF2/KEAP1 and inhibit ASAH1 expression through the ROS/AKT signalling pathway, thus suppressing cell proliferation. MCL could be used as a potential treatment for TAMR-BC.

18.
Chemosphere ; 362: 142640, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38901697

ABSTRACT

Exogenous quorum sensing (QS) molecular can regulate the activity and granulation process of anaerobic sludge in anaerobic digestion process, but would be impractical as a standalone operation. Here we demonstrated that application of 1 mg L-1 boric acid assisted in an upflow anaerobic sludge blanket (UASB) reactor recovery from volatile fatty acids (VFAs) accumulation. After VFAs accumulation, the chemical oxygen demand (COD) removal suddenly reduced from 78.98% to 55.86%. The relative abundance of acetoclastic methanogens decreased from 55.79% to 68.28%-23.14%∼25.41%, and lead to the acetate accumulate as high as 1317.03 mg L-1. Granular sludge disintegrated and the average size of sludge decreased to 586.38 ± 42.45 µm. Application of 1 mg L-1 boric acid activated the interspecies QS signal (AI-2) and then induced the secretion of intraspecies QS signal (N-acyl-homoserine lactones, AHLs). AHLs were then stimulated the growth of syntrophic acetate oxidizing bacteria and hydrogenotrophic methanogen. Moreover, the concentration of acetate decreased to 224.50 mg‧L-1, and the COD removal increased to 75.10% after application of 1 mg L-1 boric acid. The activated AI-2 may induce multiple quorum-sensing circuits enhance the level of AI-2 and AHLs in parallel, and in turn assisted in anaerobic digestion recovery from VFAs accumulation.


Subject(s)
Bioreactors , Fatty Acids, Volatile , Quorum Sensing , Sewage , Fatty Acids, Volatile/metabolism , Anaerobiosis , Sewage/microbiology , Bioreactors/microbiology , Boron , Waste Disposal, Fluid/methods , Boric Acids/metabolism , Biological Oxygen Demand Analysis , Bacteria/metabolism , Acyl-Butyrolactones/metabolism
19.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1089-1097, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38856421

ABSTRACT

In hyperspectral images, every pixel encompasses continuous spectral information. Compared with traditional colorimeters, using hyperspectral imaging systems (HIS) for fabric color measurement can result in obtaining richer color information. However, measuring fabric colors with liquid crystal tunable filter HIS can lead to challenges related to light consistency. In this paper, we adopted an innovative approach, integrating gradient boosted decision trees with a sliding window algorithm to develop a uniformity calibration model addressing the illumination uniformity issue. To address the consistency issues across various light sources, we further adopted a deep neural network (DNN) model to correct the reflectance measurements under different light sources. Subsequently, this model was merged with the uniformity calibration model to form a light-consistency correction model. Through calibration, we successfully reduced the color difference of the corrected samples from 3.636 to 0.854, an enhancement of 76.51%. This means that after calibration we can achieve consistency in fabric color measurements under nonuniform lighting and different light sources.

20.
J Hazard Mater ; 472: 134516, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38714056

ABSTRACT

There are many heavy metal stresses in agricultural biological systems, especially cadmium (Cd) stress, which prevent the full growth of plants, lead to a serious decline in crop yield, and endanger human health. Molybdenum (Mo), an essential nutrient element for plants, regulates plant growth mainly by reducing the absorption of heavy metals and protecting plants from oxidative damage. The aim of this study was to determine the protective effect of Mo (1 µM) application on wheat plants under conditions of Cd (10 µM) toxicity. The biomass, Cd and Mo contents, photosynthesis, leaf and root ultrastructure, antioxidant system, and active oxygen content of the wheat plants were determined. Mo increased the total chlorophyll content of wheat leaves by 43.02% and the net photosynthetic rate by 38.67%, and ameliorated the inhibitory effect of cadmium on photosynthesis by up-regulating photosynthesis-related genes and light-trapping genes. In addition, Mo reduced the content of superoxide anion (O2•-) by 16.55% and 31.12%, malondialdehyde (MDA) by 20.75% and 7.17%, hydrogen peroxide (H2O2) by 24.69% and 8.17%, and electrolyte leakage (EL) by 27.59% and 16.82% in wheat leaves and roots, respectively, and enhanced the antioxidant system to reduce the burst of reactive oxygen species and alleviate the damage of Cd stress on wheat. According to the above results, Mo is considered a plant essential nutrient that enhances Cd tolerance in wheat by limiting the absorption, accumulation and transport of Cd and by regulating antioxidant defence mechanisms. ENVIRONMENTAL IMPLICATION: Cadmium (Cd),is one of the most toxic heavy metals in the environment, and Cd pollution is a global environmental problem that threatens food security and human health. Molybdenum (Mo), as an essential plant nutrient, is often used to resist environmental stress. However, the mechanism of Mo treatment on wheat subjected to Cd stress has not been reported. In this study, we systematically analysed the effects of Mo on the phenotype, physiology, biochemistry, ultrastructure and Cd content of wheat subjected to Cd stress, and comprehensively analysed the transcriptomics. It not only reveals the mechanism of Mo tolerance to Cd stress in wheat, but also provides new insights into phytoremediation and plant growth in Cd-contaminated soil.


Subject(s)
Cadmium , Molybdenum , Photosynthesis , Plant Leaves , Triticum , Triticum/drug effects , Triticum/metabolism , Triticum/genetics , Cadmium/toxicity , Molybdenum/toxicity , Plant Leaves/drug effects , Plant Leaves/metabolism , Photosynthesis/drug effects , Plant Roots/drug effects , Plant Roots/metabolism , Soil Pollutants/toxicity , Antioxidants/metabolism , Transcriptome/drug effects , Chlorophyll/metabolism , Hydrogen Peroxide , Oxidative Stress/drug effects , Malondialdehyde/metabolism , Gene Expression Regulation, Plant/drug effects
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