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1.
Medicine (Baltimore) ; 103(23): e38484, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847679

ABSTRACT

The correlation between hematopoietic cell-specific lyn substrate 1 (HCLS1) expression levels and heart failure (HF) remains unclear. HF datasets GSE192886 and GSE196656 profiles were generated from GPL24676 and GPL20301 platforms in gene expression omnibus (GEO) database and differentially expressed genes (DEGs) were obtained, which was followed by weighted gene co-expression network analysis, protein-protein interaction (PPI) networks, functional enrichment analysis and comparative toxicogenomics database (CTD) analysis. Heatmaps of gene expression levels were plotted. TargetScan was used to screen miRNAs regulating central DEGs. A total of 500 DEGs were found and mainly concentrated in leukocyte activation, protein phosphorylation, and protein complexes involved in cell adhesion, PI3K Akt signaling pathway, Notch signaling pathway, and right ventricular cardiomyopathy. PPI network identified 15 core genes (HCLS1, FERMT3, CD53, CD34, ITGAL, EP300, LYN, VAV1, ITGAX, LEP, ITGB1, IGF1, MMP9, SMAD2, RAC2). Heatmap shows that 4 genes (EP300, CD53, HCLS1, LYN) are highly expressed in HF tissue samples. We found that 4 genes (EP300, CD53, HCLS1, LYN) were associated with heart diseases, cardiovascular diseases, edema, rheumatoid arthritis, necrosis, and inflammation. HCLS1 is highly expressed in HF and maybe its target.


Subject(s)
Biomarkers , Heart Failure , Humans , Heart Failure/genetics , Heart Failure/metabolism , Biomarkers/metabolism , Protein Interaction Maps/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Gene Expression Profiling
2.
Sci Total Environ ; 937: 173534, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38802020

ABSTRACT

Granite, as the natural barrier for the disposal of high-level radioactive waste, plays an important role in ensuring environmental and public safety. The safety assessment of the repository depends on the reliable migration parameters of radionuclides in granite. In this study, we developed a kinetic adsorption-advection-dispersion model based on first-order adsorption kinetics. It introduces a first-order adsorption rate coefficient to describe the kinetics of adsorption process and accounts for other crucial mechanisms affecting the migration of radionuclide ions, namely, the electromigration, electroosmosis, and dispersion. This model is then applied to interpret the experimental results of electromigration of tracer ions in intact granite. The results show that for the weakly adsorbed radionuclides studied, iodide and selenite, the effective diffusion coefficients and formation factors calculated by this model are in constant with those derived from the classical advection-dispersion model based on linear adsorption equilibrium. By contrast, for the moderately or strongly adsorbed tracer ions studied, including cobalt, cesium, and strontium, the migration parameters calculated by this model exhibit significantly less uncertainty than those obtained from the advection-dispersion model simulations. The advection-dispersion model based on the first order adsorption kinetics introduces the first order adsorption rate coefficient, and considers the influence of electromigration, electroosmosis and dispersion mechanism, which helps to explain the migration mechanism of nuclide ions in intact granite more accurately.

3.
Nano Lett ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38620050

ABSTRACT

Understanding the structure-performance relationships of a frustrated Lewis pair (FLP) at the atomic level is key to yielding high efficiency in activating chemically "inert" molecules into value-added products. A sound strategy was developed herein through incorporating oxygen defects into a Zr-based metal-organic layer (Zr-MOL-D) and employing Lewis basic proximal surface hydroxyls for the in situ formation of solid heterogeneous FLP (Zr4-δ-VO-Zr-OH). Zr-MOL-D exhibits a superior CO2 to CO conversion rate of 49.4 µmol g-1 h-1 in water vapor without any sacrificing agent or photosensitizer, which is about 12 times higher than that of pure MOL (Zr-MOL-P), with extreme stability even after being placed for half a year. Theoretical and experimental results reveal that the introduction of FLP converts the process of the crucial intermediate COOH* from an endothermic reaction to an exothermic spontaneous reaction. This work is expected to provide new prospects for developing efficient MOL-based photocatalysts in FLP chemistry through a sound defect-engineering strategy.

4.
Mikrochim Acta ; 191(5): 259, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38605266

ABSTRACT

A three-dimensional (3D) self-assembled AuNPs/Ti3C2 MXene hydrogel (AuNPs/Ti3C2 MXH) nanocomposite was prepared for the fabrication of a novel microRNA-122 electrochemical biosensor. The 3D hydrogel structure was gelated from two-dimensional MXene nanosheets with the assistance of graphite oxide and ethylenediamine. MXene hydrogels supported the in situ formation of Au nanoparticles (AuNPs) that predominantly exploring the (111) facet, and these AuNPs are utilized as carriers for hairpin DNA (hpDNA) probes, facilitating DNA hybridization. MXene acted as both a reductant and stabilizer, significantly improving the electrochemical signal. In addition, the conjugation of PAMAM dendrimer-encapsulated AuNPs and H-DNA worked as an ideal bridge to connect targets and efficient electrochemical tags, providing a high amplification efficiency for the sensing of microRNA-122. A linear relationship between the peak currents and the logarithm of the concentrations of microRNA-122 from 1.0 × 10-2 to 1.0 × 102 fM (I = 1.642 + 0.312 lgc, R2 = 0.9891), is obtained. The detection limit is  0.8 × 10-2 fM (S/N = 3). The average recovery for human serum detection ranged from 97.32 to 101.4% (RSD < 5%).


Subject(s)
Metal Nanoparticles , MicroRNAs , Nitrites , Transition Elements , Humans , Gold/chemistry , Metal Nanoparticles/chemistry , Hydrogels , Titanium/chemistry , DNA/chemistry
5.
Analyst ; 149(9): 2756-2761, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38563766

ABSTRACT

New dynamic, wireless and cost-effective analytical devices are developing rapidly in biochemical analysis. Here, we report on a remotely-controlled rotating electrochemiluminescence (ECL) sensing system for enzymatic detection of a model analyte, glucose, on both polarized sides of an iron wire acting as a bipolar electrode. The iron wire is controlled by double contactless mode, involving remote electric field polarization, and magnetic field-induced rotational motion. The former triggers the interfacial polarization of both extremities of the wire by bipolar electrochemistry, which generates ECL emission of the luminol derivative (L-012) with the enzymatically produced hydrogen peroxide in presence of glucose, at both anodic and cathodic poles, simultaneously. The latter generates a convective flow, leading to an increase in mass transfer and amplifying the corresponding ECL signals. Quantitative glucose detection in human serum samples is achieved. The ECL signals were found to be a linear function of the glucose concentration within the range of 10-1000 µM and with a limit of detection of 10 µM. The dynamic bipolar ECL system simultaneously generates light emissions at both anodic and cathodic poles for glucose detection, which can be further applied to biosensing and imaging in autonomous devices.


Subject(s)
Electrochemical Techniques , Luminescent Measurements , Luminescent Measurements/methods , Humans , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Electrodes , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Limit of Detection , Blood Glucose/analysis , Wireless Technology , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Luminol/chemistry
6.
In Vitro Cell Dev Biol Anim ; 60(4): 382-396, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38625487

ABSTRACT

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers. The AOM/DSS mouse model of colorectal cancer was constructed. The expression levels of JAML, CXADR and PD-1 were detected by PCR and Western blot, and the proportion of CD8+ T cells and exhausted T cells were detected by flow cytometry. The expression levels of JAML and CXADR were significantly decreased in colon cancer tissues. Overexpression of JAML can promote the proliferation of T cells, secrete a variety of inflammatory factors. Overexpression of CXADR can reduce the proliferation of colorectal cancer cells, promote apoptosis, and down-regulate the migration and invasion ability of tumor cells. Both JAML agonists and PD-L1 inhibitors can effectively treat colorectal cancer, and the combined use of JAML agonists and PD-L1 inhibitors can enhance the effect. JAML can promote the proliferation and toxicity of CD8+ T cells and down-regulate the expression of immune checkpoints in colon cancer. CXADR can inhibit the proliferation of cancer cells and promote the apoptosis. JAML agonist can effectively treat colorectal cancer by regulating CD8+ T cells.


Subject(s)
Carcinogenesis , Colorectal Neoplasms , Tumor Microenvironment , Animals , Humans , Male , Mice , Apoptosis/drug effects , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Carcinogenesis/drug effects , Carcinogenesis/immunology , Carcinogenesis/genetics , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic/drug effects , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
7.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38492559

ABSTRACT

OBJECTIVES: Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample. METHODS: We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method. RESULTS: This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality. CONCLUSIONS: Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.


Subject(s)
Esophageal Neoplasms , Respiratory Insufficiency , Humans , Esophagectomy/adverse effects , Esophagectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , China/epidemiology , Esophageal Neoplasms/complications , Risk Factors , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/etiology , Retrospective Studies , Minimally Invasive Surgical Procedures/methods
8.
Front Nutr ; 11: 1372982, 2024.
Article in English | MEDLINE | ID: mdl-38533461

ABSTRACT

A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC-MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 µg/mL Dex + 2,400 µg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 µg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

9.
Biol Direct ; 19(1): 20, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454507

ABSTRACT

CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.


Subject(s)
Carcinoma , MicroRNAs , Urinary Bladder Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder/metabolism , Urinary Bladder/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Carcinoma/genetics , Cell Movement , Gene Expression Regulation, Neoplastic , Membrane Glycoproteins/metabolism
10.
Article in English | MEDLINE | ID: mdl-38231812

ABSTRACT

Neural architecture search (NAS) has shown great promise in automatically designing neural network models. Recently, block-wise NAS has been proposed to alleviate deep coupling problem between architectures and weights existed in the well-known weight-sharing NAS, by training the huge weight-sharing supernet block-wisely. However, the existing block-wise NAS methods, which resort to either supervised distillation or self-supervised contrastive learning scheme to enable block-wise optimization, take massive computational cost. To be specific, the former introduces an external high-capacity teacher model, while the latter involves supernet-scale momentum model and requires a long training schedule. Considering this, in this work, we propose a resource-friendly deeply supervised block-wise NAS (DBNAS) method. In the proposed DBNAS, we construct a lightweight deeply-supervised module after each block to enable a simple supervised learning scheme and leverage ground-truth labels to indirectly supervise optimization of each block progressively. Besides, the deeply-supervised module is specifically designed as structural and functional condensation of the supernet, which establishes global awareness for progressive block-wise optimization and helps search for promising architectures. Experimental results show that the DBNAS method only takes less than 1 GPU day to search out promising architectures on the ImageNet dataset with less GPU memory footprint than the other block-wise NAS works. The best-performing model among the searched DBNAS family achieves 75.6% Top-1 accuracy on ImageNet, which is competitive with the state-of-the-art NAS models. Moreover, our DBNAS family models also achieve good transfer performance on CIFAR-10/100, as well as two downstream tasks: object detection and semantic segmentation.

11.
Cell Signal ; 117: 111066, 2024 05.
Article in English | MEDLINE | ID: mdl-38281617

ABSTRACT

Lung adenocarcinoma (LUAD) is the most commonly diagnosed subtype of lung cancer worldwide. Inhibitor of growth 3 (ING3) serves as a tumor suppressor in many cancers. This study aimed to elucidate the role of ING3 in the progression of LUAD and investigate the underlying mechanism related to integrin ß4 (ITGB4) and Src/focal adhesion kinase (FAK) signaling. ING3 expression in LUAD tissues and the correlation between ING3 expression and prognosis were analyzed by bioinformatics databases. After evaluating ING3 expression in LUAD cells, ING3 was overexpressed to assess the proliferation, cell cycle arrest, migration and invasion of LUAD cells. Then, ITGB4 was upregulated to observe the changes of malignant activities in ING3-overexpressed LUAD cells. The transplantation tumor model of NCI-H1975 cells in nude mice was established to analyze the antineoplastic effect of ING3 upregulation in vivo. Downregulated ING3 expression was observed in LUAD tissues and cells and lower ING3 expression predicated the poor prognosis. ING3 upregulation restrained the proliferation, migration, invasion and induced the cell cycle arrest of NCI-H1975 cells. Additionally, ITGB4 expression was negatively correlated with ING3 expression in LUAD tissue. ING3 led to reduced expression of ITGB4, Src and p-FAK. Moreover, ITGB4 overexpression alleviated the effects of ING3 upregulation on the malignant biological properties of LUAD cells. It could be also found that ING3 upregulation limited the tumor volume, decreased the expression of ITGB4, Src and p-FAK, which was restored by ITGB4 overexpression. Collectively, ING3 inhibited the malignant progression of LUAD by negatively regulating ITGB4 expression to inactivate Src/FAK signaling.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Animals , Mice , Adenocarcinoma/metabolism , Adenocarcinoma of Lung/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Gene Expression Regulation, Neoplastic , Integrin beta4/genetics , Lung Neoplasms/metabolism , Mice, Nude , src-Family Kinases , Humans
12.
J Thorac Cardiovasc Surg ; 167(3): 838-847.e1, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37696429

ABSTRACT

OBJECTIVE: This study aims to report the 2-year outcomes of patients with clinical stage N2-3 esophageal squamous cell carcinoma who received neoadjuvant chemotherapy and immunotherapy followed by surgery from a phase 2 NICE trial. METHODS: Eligible patients with clinical stage N2-3 esophageal squamous cell carcinoma were screened and enrolled, then treated with regimen of nab-paclitaxel (100 mg/m2, days 1, 8, 15), carboplatin (area under the curve = 5, day 1), camrelizumab (200 mg, day 1) of two 21-day cycles and esophagectomy 4 to 6 weeks after the last chemotherapy. Oncologic outcomes, recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) were explored. RESULTS: From November 20, 2019, to December 22, 2020, 60 patients were recruited. After a median follow-up of 27.4 months, disease recurrence was observed in 19 (37.3%) patients, with 5 (9.8%) locoregional recurrence, 9 (17.6%) distant metastasis, and 5 (9.8%) combined recurrence. Lung was the most commonly involved metastatic site. The median time to recurrence was 10.8 months (interquartile range, 7.5-12.7 months). The 2-year OS and RFS rates were 78.1% and 67.9%, respectively. Patients who achieved major pathologic response (MPR) had a significantly greater 2-year OS rate (91.4% vs 47.7%; P < .001) and RFS rate (77.1% vs 45.9%; P = .003). On multivariable analysis, MPR was indicated as an independent prognostic factor for disease recurrence (hazard ratio, 0.39; 95% confidence interval, 0.21-0.82; P = .029). CONCLUSIONS: In patients receiving neoadjuvant chemotherapy and immunotherapy, distant metastasis remains the predominant recurrence pattern. MPR is associated with lower recurrence and better survival. Long-term results derived from randomized controlled trials are further required. TRIAL REGISTRATION NUMBER: ChiCTR1900026240.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Cisplatin , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/pathology , Immunotherapy
13.
Front Oncol ; 13: 1198592, 2023.
Article in English | MEDLINE | ID: mdl-37941542

ABSTRACT

Objective: Colon cancer with retroperitoneal abscess is a rare and easily misdiagnosed disease and has only been reported via case. There is an urgent need to conduct a dataset analysis for such patients, which is crucial to improving the survival rate and quality of life of these patients. Methods: Patients with colon cancer associated with retroperitoneal abscess were extracted from our hospital and the PubMed, EMBASE and Web of Science databases. Clinical information, including the patients' basic characteristics, clinical symptoms, laboratory tests, imaging examinations, treatment methods and prognosis was analyzed. Results: Sixty-one patients were analyzed, with an average age of 65 years. The proportions of right and left colon cancers were 63.9% and 36.1%, respectively. A total of 98.0% of the patients had adenocarcinoma. Many patients have insidious symptoms such as fever and weight loss. At the first medical visit, pain was the most common symptom (71%), with pain in the thigh (21.8%), abdomen (21.8%), and waist and back (14.5%) ranking among the top three. The misdiagnosis rate of the patients referred to our department was 75%, while the overall misdiagnosis rate in the literature was 43.9%. Laboratory tests show that these patients often have elevated white blood cells and anemia. CT examination showed that 87.2% of patients had an iliopsoas muscle abscess, and tumors were not simultaneously detected in 37.2%. A total of 33.9% of patients had local abscesses of the iliopsoas muscle, 26.4% had drainage into the subcutaneous tissue of the waist and upper buttocks, and 22.6% had drainage around the adductor muscle group of the thigh. These patients have a variety of treatments, and many patients have undergone multiple and unnecessary treatments. Thirteen patients died after surgery, and 6 died in the hospital, of whom four were patients undergoing direct surgery, and the other 7 died after discharge due to cachexia. Conclusion: Colorectal cancer with retroperitoneal abscess is a relatively rare and easily misdiagnosed subtype of colon cancer. It is more likely to occur in right-sided colon adenocarcinoma. The main clinical symptom is pain caused by the drainage of pus to the corresponding areas of the waist, abdomen, and legs. CT is the preferred diagnostic method. Actively treating the abscess and then transitioning to standard colon cancer treatment can prevent patient death and improve treatment quality.

14.
Int Immunopharmacol ; 125(Pt A): 111167, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37931392

ABSTRACT

Regulatory T cells (Tregs) have critical roles in maintaining immune hemostasis and have important anti-inflammatory functions in diseases. Recently, we identified that CX-5461 (a selective RNA polymerase I inhibitor and p53 activator) acted as a potent immunosuppressive agent, which prevented allogeneic acute rejection in animal models via a molecular mechanism distinct from all those of conventional immunosuppressive drugs. Unexpectedly, we discovered that CX-5461 could promote Treg differentiation. In this review, we have summarized the evidence for a potential role of p53 in mediating Treg differentiation and its possible mechanisms, including regulation of FoxP3 transcription, regulation of the expression of PTEN (phosphatase and tensin homolog), as well as protein-protein interaction with the transcription factor STAT5 (signal transducer and activator of transcription 5). Evidence also suggests that pharmacological p53 activators may potentially be used to boost Treg-mediated immune tolerance. Based on these data, we argue that novel p53 activators such as CX-5461 may represent a distinct class of immunosuppressants that repress conventional T cell-mediated alloimmunity with concomitant boosting of Treg-dependent immune tolerance.


Subject(s)
T-Lymphocytes, Regulatory , Tumor Suppressor Protein p53 , Animals , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Immune Tolerance , Gene Expression Regulation , Forkhead Transcription Factors/metabolism
15.
Int J Mol Sci ; 24(20)2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37894734

ABSTRACT

The gut microbiota undergoes metabolic processes to produce by-products (gut metabolites), which play a vital role in the overall maintenance of health and prevention of disease within the body. However, the use of gut metabolites as anticancer agents and their molecular mechanisms of action are largely unknown. Therefore, this study evaluated the anti-proliferative effects of three key gut microbial metabolites-sodium butyrate, inosine, and nisin, against MCF7 and MDA-MB-231 breast adenocarcinoma cell lines. To determine the potential mechanistic action of these gut metabolites, flow cytometric assessments of apoptotic potential, reactive oxygen species (ROS) production measurements and proteomics analyses were performed. Sodium butyrate exhibited promising cytotoxicity, with IC50 values of 5.23 mM and 5.06 mM against MCF7 and MDA-MB-231 cells, respectively. All three metabolites were found to induce apoptotic cell death and inhibit the production of ROS in both cell lines. Nisin and inosine indicated a potential activation of cell cycle processes. Sodium butyrate indicated the possible initiation of signal transduction processes and cellular responses to stimuli. Further investigations are necessary to ascertain the effective therapeutic dose of these metabolites, and future research on patient-derived tumour spheroids will provide insights into the potential use of these gut metabolites in cancer therapy.


Subject(s)
Adenocarcinoma , Gastrointestinal Microbiome , Nisin , Humans , Nisin/pharmacology , Butyric Acid/pharmacology , Reactive Oxygen Species/metabolism , Adenocarcinoma/drug therapy , Inosine
17.
J Am Chem Soc ; 145(31): 17309-17320, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37525440

ABSTRACT

Organic materials are promising for cation storage in calcium ion batteries (CIBs). However, the high solubility of organic materials in an electrolyte and low electronic conductivity remain the key challenges for high-performance CIBs. Herein, a nitrogen-rich covalent organic framework with multiple carbonyls (TB-COF) is designed as an aqueous anode to address those obstacles. TB-COF demonstrates a high reversible capacity of 253 mAh g-1 at 1.0 A g-1 and long cycle life (0.01% capacity decay per cycle at 5 A g-1 after 3000 cycles). The redox mechanism of Ca2+/H+ co-intercalated in COF and chelating with C═O and C═N active sites is validated. In addition, a novel C═C active site was identified for Ca2+ ion storage. Both computational and empirical results reveal that per TB-COF repetitive unit, up to nine Ca2+ ions are stored after three staggered intercalation steps, involving three distinct Ca2+ ion storage sites. Finally, the evolution process of radical intermediates further elucidates the C═C reaction mechanism.

18.
Front Neurorobot ; 17: 1205775, 2023.
Article in English | MEDLINE | ID: mdl-37614967

ABSTRACT

Considering the dynamics and non-linear characteristics of biped robots, gait optimization is an extremely challenging task. To tackle this issue, a parallel heterogeneous policy Deep Reinforcement Learning (DRL) algorithm for gait optimization is proposed. Firstly, the Deep Deterministic Policy Gradient (DDPG) algorithm is used as the main architecture to run multiple biped robots in parallel to interact with the environment. And the network is shared to improve the training efficiency. Furthermore, heterogeneous experience replay is employed instead of the traditional experience replay mechanism to optimize the utilization of experience. Secondly, according to the walking characteristics of biped robots, a biped robot periodic gait is designed with reference to sinusoidal curves. The periodic gait takes into account the effects of foot lift height, walking period, foot lift speed and ground contact force of the biped robot. Finally, different environments and different biped robot models pose challenges for different optimization algorithms. Thus, a unified gait optimization framework for biped robots based on the RoboCup3D platform is established. Comparative experiments were conducted using the unified gait optimization framework, and the experimental results show that the method outlined in this paper can make the biped robot walk faster and more stably.

19.
Front Hum Neurosci ; 17: 1205858, 2023.
Article in English | MEDLINE | ID: mdl-37554408

ABSTRACT

Accurate recognition of patients' movement intentions and real-time adjustments are crucial in rehabilitation exoskeleton robots. However, some patients are unable to utilize electromyography (EMG) signals for this purpose due to poor or missing signals in their lower limbs. In order to address this issue, we propose a novel method that fits gait parameters using cerebral blood oxygen signals. Two types of walking experiments were conducted to collect brain blood oxygen signals and gait parameters from volunteers. Time domain, frequency domain, and spatial domain features were extracted from brain hemoglobin. The AutoEncoder-Decoder method is used for feature dimension reduction. A regression model based on the long short-term memory (LSTM) model was established to fit the gait parameters and perform incremental learning for new individual data. Cross-validation was performed on the model to enhance individual adaptivity and reduce the need for individual pre-training. The coefficient of determination (R2) for the gait parameter fit was 71.544%, with a mean square error (RMSE) of less than 3.321%. Following adaptive enhancement, the coefficient of R2 increased by 6.985%, while the RMSE decreased by 0.303%. These preliminary results indicate the feasibility of fitting gait parameters using cerebral blood oxygen information. Our research offers a new perspective on assisted locomotion control for patients who lack effective myoelectricity, thereby expanding the clinical application of rehabilitation exoskeleton robots. This work establishes a foundation for promoting the application of Brain-Computer Interface (BCI) technology in the field of sports rehabilitation.

20.
Article in English | MEDLINE | ID: mdl-37432819

ABSTRACT

Modeling the architecture search process on a supernet and applying a differentiable method to find the importance of architecture are among the leading tools for differentiable neural architectures search (DARTS). One fundamental problem in DARTS is how to discretize or select a single-path architecture from the pretrained one-shot architecture. Previous approaches mainly exploit heuristic or progressive search methods for discretization and selection, which are not efficient and easily trapped by local optimizations. To address these issues, we formulate the task of finding a proper single-path architecture as an architecture game among the edges and operations with the strategies "keep" and "drop" and show that the optimal one-shot architecture is a Nash equilibrium of the architecture game. Then, we propose a novel and effective approach for discretizing and selecting a proper single-path architecture, which is based on extracting the single-path architecture that associates the maximal coefficient of the Nash equilibrium with the strategy "keep" in the architecture game. To further improve the efficiency, we employ a mechanism of entangled Gaussian representation of mini-batches, inspired by the classic Parrondo's paradox. If some mini-batch formed uncompetitive strategies, the entanglement of mini-batches would ensure the games be combined and, thus, turn into strong ones. We conduct extensive experiments on benchmark datasets and demonstrate that our approach is significantly faster than the state-of-the-art progressive discretizing methods while maintaining competitive performance with higher maximum accuracy.

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