The current state of MRI-based radiomics in pituitary adenoma: promising but challenging.

In the clinical diagnosis and treatment of pituitary adenomas, MRI plays a crucial role. However, traditional manual interpretations are plagued by inter-observer variability and limitations in recognizing details. Radiomics, based on MRI, facilitates quantitative analysis by extracting high-throughput data from images. This approach elucidates correlations between imaging features and pituitary tumor characteristics, thereby establishing imaging biomarkers. Recent studies have demonstrated the extensive application of radiomics in differential diagnosis, subtype identification, consistency evaluation, invasiveness assessment, and treatment response in pituitary adenomas. This review succinctly presents the general workflow of radiomics, reviews pertinent literature with a summary table, and provides a comparative analysis with traditional methods. We further elucidate the connections between radiological features and biological findings in the field of pituitary adenoma. While promising, the clinical application of radiomics still has a considerable distance to traverse, considering the issues with reproducibility of imaging features and the significant heterogeneity in pituitary adenoma patients.

Losartan rewires the tumor-immune microenvironment and suppresses IGF-1 to overcome resistance to chemo-immunotherapy in ovarian cancer.

BACKGROUND: Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. METHODS: Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. RESULTS: Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. CONCLUSION: The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.

Enhancing vaccine efficacy: Evaluating the superiority of cationic liposome-embedded squalene adjuvant against PCV2 infection.

Cationic liposome-embedded squalene (CLS) is a promising adjuvant that enhances antigen stability and mobility and improves immune response. This study compares the efficacy of a CLS-adjuvant porcine circovirus type 2 (PCV2) vaccine (CSV) with a conventional vaccine against PCV2. The CSV vaccine showed superior stability and was effective against PCV2-induced growth decline. It significantly increased serum immunoglobulin and cytokine levels, reduced serum PCV2 DNA, shortened the duration of viremia, and provided robust protection. CSV outperformed conventional vaccines, highlighting its potential for innovative vaccine development.

Microenvironment-responsive nano-bioconjugated vesicles for the multi-pronged treatment of liver fibrosis.

Liver fibrosis represents an inevitable stage of various chronic liver diseases. The activated hepatic stellate cells (aHSCs) are the main drivers for promoting the development of liver fibrosis. Meanwhile, liver macrophages can secrete pro-inflammatory cytokines, thus accelerating the deterioration of the liver. Regulating both aHSCs and the inflammatory microenvironment in the liver simultaneously may be an effective strategy for treating liver fibrosis. A multi-pronged nano-bioconjugated system, HNP-B-aEV, was developed according to the above strategy. Based on cell aggregate-derived extracellular vesicles (aEVs) and hydroxychloroquine (HCQ)-loaded nanoparticles (HNP) modified with retinol, HNP-B-aEV is prepared via a reactive oxygen species (ROS)-responsive boronate linker. In the ROS-rich microenvironment of liver fibrosis, aEVs and HNP are released, eliminating ROS, and targeting aHSCs and macrophages respectively to inhibit the activation of HSCs. Both in vitro and in vivo studies demonstrated that HNP-B-aEV can significantly inhibit the release of inflammatory factors from M1 macrophages, remodeling the microenvironment and preventing the activation of HSCs, offering a multi-pronged treatment for liver fibrosis. This strategy can inhibit the progression of liver fibrosis at its source, providing a new perspective for the clinical treatment of liver fibrosis.

Risk assessment of Arsenic in surface water of China water systems based on a time-dependent species sensitivity distribution (SSD) method.

Arsenic (As) is a naturally occurring metalloid element widespread in the environment. Assessing the ecological risk of As in surface water, especially the acute risk caused by emergent pollution incidents, is of great significance. However, acute toxicity data including median lethal concentration (LC50) and median effective concentration (EC50) of As derived by toxicology experiment may vary according to the exposure time, which is referred as time dependence effect. Time dependence not only affects toxicity data but also influences the characterization of acute risk in the ecosystem. However, previous research on the time dependence effect of As, especially the quantitative influence on the risk assessment is still limited. In this research, acute toxicity data of As(III) and As(V) was collected. Time dependence of toxicology data of inorganic As was studied. Time-dependent species sensitivity distributions of freshwater species were established. The hazardous concentration for 5% of species (HC5) values in different exposure time were further derived. Finally, the dynamic ecological risk of As in major Chinese water basins was evaluated. The results suggested that the toxicity data of inorganic As had a significant linear relationship (p < 0.01) with time. The HC5 values of As (III) and As (V) at an exposure time of four days were reduced by 15.5% and 77.5%, respectively, as compared to the HC5 value of one day. According to the ecological risk characterized by the probability density overlapping area method, the ecological risk of As(III) and As(V) increases with the exposure duration. The Yangtze River had the highest risk, with risk values ranging from 19.9% to 22.6%. According to the results, the time dependence of toxicity data should be fully considered in the formulation of water quality criteria or ecological risk assessment so as to provide better protection for the water ecosystem security.

Relationships Between Quality of Discharge Teaching, Readiness for Hospital Discharge, Self-Efficacy and Self-Management in Patients With First-Episode Stroke: A Cross-Sectional Study.

AIMS: The study investigated the influence of quality of discharge teaching (QDT) on readiness for hospital discharge (RHD) and pathways involved in patients with first-episode stroke, aiming to provide a theoretical framework for enhancing RHD levels and reducing readmission rates. DESIGN: Cross-sectional study. METHODS: A total of 372 inpatients completed the Quality of Discharge Teaching Scale, Readiness for Hospital Discharge Scale, Chronic Disease Self-efficacy Scale and Southampton Stroke Self-Management Questionnaire. Structural equation modelling and Pearson's correlation analysis were utilised to elucidate relationships and action pathways among these variables. RESULTS: The correlation analysis demonstrated significant positive pairwise correlations between QDT, RHD, self-efficacy and self-management (r = 0.376-0.678, p < 0.01). The final model exhibited a good fit with the following indices: χ2/df = 3.286, RMSEA = 0.078, SRMR = 0.0303, GFI = 0.984, AGFI = 0.926, CFI = 0.991 and TLI = 0.970. The impact of QDT on RHD in patients with first-episode stroke was observed through one direct and three indirect pathways: (1) QDT exerted a direct influence on RHD (p < 0.001); (2) QDT indirectly influenced RHD via self-efficacy (p < 0.001); (3) QDT indirectly affected RHD through self-management (p < 0.001); and (4) QDT had an indirect effect on RHD via both self-efficacy and self-management (p < 0.05). CONCLUSION: QDT was found to directly influence RHD in patients with first-episode stroke and also exerted indirect effects through self-efficacy and self-management, either independently or in combination. Early screening of RHD levels in patients before discharge is recommended, along with the enhancement of QDT through the development of tailored guidance plans according to different disease stages, ultimately improving RHD levels and facilitating a safer transition from hospital to home or community. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should assess both QDT and RHD levels to provide targeted interventions. The establishment of transitional care teams and implementation of long-term poststroke management are essential for reducing stroke recurrence and mortality rates.

More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis.

We investigated the association between cerebral small vessel disease (CSVD) and ipsilateral leptomeningeal collateral (LMC) status in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). In 108 patients with 50-99% symptomatic intracranial internal carotid artery or M1 middle cerebral artery stenosis, 4 CSVD imaging markers (lacunes, cerebral microbleeds, enlarged perivascular spaces [EPVSs], and white matter hyperintensities [WMHs]) were assessed in MRI. Score of 0 or 1 was assigned to each marker and added up as a summary CSVD score (ranging 0-4) to reflect an overall CSVD burden. Ipsilateral LMC status was assessed by determining the laterality of distal vessels in anterior and posterior cerebral artery territories on CT angiography. Moderate-to-severe EPVSs (adjusted odds ratio [aOR] = 4.15; p = 0.031) and WMHs (aOR = 5.90; p = 0.010), and higher summary CSVD score (aOR = 1.66; p = 0.030) were independently associated with poor LMCs. There was significant interaction between stenosis percentage in sICAS and summary CSVD score on poor LMCs (p = 0.022 for interaction), when higher CSVD score was significantly associated with poor LMCs in patients with severe sICAS (aOR = 2.84; p = 0.011) but not in those with moderate sICAS. The findings indicated possibly adverse effect of CSVD on the recruitment or development of LMCs in sICAS patients, especially in patients with severe sICAS.

Ephrin A1 Stimulates CCL2 Secretion to Facilitate Pre-metastatic Niche Formation and Promote Gastric Cancer Liver Metastasis.

The liver is a primary target for distal metastasis of gastric cancer (GC). The hepatic pre-metastatic niche (PMN) facilitates crucial communications between primary tumor and liver, thereby playing an essential role in hepatic metastasis. Identification of the molecular mechanisms driving PMN formation in GC could facilitate development of strategies to prevent and treat liver metastasis. Here, we uncovered a role for ephrin A1 (EFNA1) signaling in development of the PMN. EFNA1 overexpression in GC cells significantly increased CCL2 secretion through the Hippo-YAP pathway. Secreted CCL2 activated hepatic stellate cells (HStCs) within the hepatic PMN via the WNT/ß-catenin pathway. Inhibition of CCL2 significantly suppressed HStC activation and reduced liver metastasis triggered by EFNA1 signaling in GC cells. Moreover, high CCL2 expression correlated with poor survival in GC patients. Overall, these findings reveal that EFNA1 signaling in GC cells upregulates CCL2, which activates HStCs to engender establishment of a hepatic pre-metastatic niche that supports liver metastasis.

Fluorescence in situ hybridization analysis of Oligonucleotide 5S rDNA, 45S rDNA, and (TTTAGGG)3 locations in Gloriosa superba L.

INTRODUCTION: Gloriosa superba L. is a horticulturally and medicinally important plant native to Africa. However, the few cytogenetic studies of the species are mainly focused on chromosome counting and chromosome morphology-based karyotyping. Fluorescence in situ hybridization (FISH) is a powerful tool for the detection of DNA repetitive elements in a specific region of a chromosome. METHODS: Here, detailed karyotypes of G. superba were constructed by FISH using 5S and 45S rDNAs, and telomeric repeat (TTTAGGG)3 oligonucleotides. RESULTS AND CONCLUSION: Twenty-two chromosomes were observed. Two 5S rDNA hybridization signals were detected in the proximal regions of the short arms of one pair of chromosomes, which were adjacent to the (TTTAGGG)3 terminal signals. Four 45S rDNA signals were detected near the centromere region of the short arm of the four chromosomes, but one of these was very weak and almost undetectable compared to the others. Telomeric repeat hybridization signals were distributed at the terminal region of each chromosome. The chromosomes displayed were intact and the chromosome counts were accurate. Chromosome length ranged from 3.46 to 9.31 µm. These results will facilitate the cytogenetic mapping of other major repeats, thus contributing to an improved understanding of the G. superba genome structure and evolutionary history.

A mechanistic review of the pharmacological aspects of Kaempferide as a natural compound.

Background: Kaempferide exhibits a range of pharmacological effects, including anti-tumor activity, kidney protection, oxidative stress relief, gastroprotection, and endocrine regulation. The increasing attention surrounding kaempferide, a promising therapeutic agent, has sparked considerable debate, making it a topic of significant interest in recent research. Purpose: This paper aims to provide a comprehensive review of the clinical applications, pharmacological properties, and underlying molecular mechanisms of kaempferide, while also examining its potential for future therapeutic applications in the field of pharmacology. Methodology: We used the keywords "kaempferide" and "kaempferide derivatives" to search for relevant articles in Science Direct, PubMed, MEDLINE, and Web of Science databases. Results: Kaempferide possesses anti-inflammatory, stomach-protective, antioxidant, anti-tumor, and anti-adipogenic activities, and thus has great potential in different systemic therapies. These interactions involve a multitude of pathways that directly or indirectly affect upstream and downstream key molecules. Conclusions: Although kaempferide has shown promising potential, its practical applications still require further in-depth investigation. Future research should prioritize elucidating its mechanisms of action, identifying specific therapeutic targets, and optimizing the compound to facilitate its translation into drug development.

A network pharmacology approach-based decoding of Resveratrol's anti-fibrotic mechanisms.

BACKGROUND: Inhalation of crystalline silica (CS) frequently leads to chronic lung inflammation and pulmonary fibrosis (PF), a condition with limited effective treatments. Resveratrol (Res) has demonstrated potential in PF treatment; however, its underlying mechanisms remain incompletely elucidated. PURPOSE: This study represents the first comprehensive attempt to uncover the novel mechanisms underlying Res's anti-fibrotic effects against PF through an innovative, integrated approach combining network pharmacology and experimental validation. METHODS: We employed network pharmacology to investigate the holistic pharmacological mechanism of Res, then validated the predicted pharmacological effects using in vivo and in vitro studies. RESULTS: In total, 216 genes were identified to be simultaneously associated with PF and Res. An integrated bioinformatics analysis implicated a crucial role of the autophagy signaling pathway in dominating PF, with AMPK and mTOR showing high docking scores. Animal studies revealed that Res significantly alleviated silica-induced lung damage in silicotic mice, with decreased collagen I (Col-I) levels and reduced expression of vimentin and α-SMA. In-depth investigation demonstrated that Res modulated CS-dysregulated autophagy by targeting the AMPK/mTOR pathway. in vitro, Res treatment significantly reduced lactate dehydrogenase (LDH), TNF-α, and TGF-ß levels and improved cell viability of Raw264.7 cells post-CS exposure. Notably, Res was demonstrated to suppress fibroblast-to-myofibroblast transition via mediating macrophage autophagy through the AMPK/mTOR pathway. CONCLUSION: Res can alleviate CS-induced PF by targeting AMPK in the autophagy signaling pathway, which sheds light on Res' therapeutic potential in treating PF.

Lemierre's syndrome associated-diabetic ketoacidosis in an elderly female: a case report.

BACKGROUND: The co-occurrence of Lemierre's syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre's syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly. CASE PRESENTATION: We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre's syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient's discharge. CONCLUSIONS: The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre's syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases.

Quercetin protects human coronary artery endothelial cells against hypoxia/reoxygenation-induced mitochondrial apoptosis via the Nrf2/HO-1 axis.

Our study explored the therapeutic effect and the mechanism of quercetin against hypoxia/reoxygenation (H/R)-induced injury in human coronary artery endothelial cells (CAECs). Quercetin was selected as a potential component for the BuShenKangShuaiPian formula (BSKSP) treatment via the Network pharmacology analysis. Cell viability and reactive oxygen species (ROS) production were measured by CCK8 assay and immunofluorescence, respectively. The expression of Bax, Bcl-2, Cle-caspase-3, cytochrome c (Cyt-C), NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein was quantified by western blotting. The superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) activity, mtDNA copy number, and ATP production were measured via corresponding kits. Quercetin was selected from the BSKSP for its high degree value (Degree value: 22). Besides, quercetin protected CAECs against H/R-induced cytotoxicity and apoptosis. The H/R-induced increased ROS level, ATP production, Cyt-C release, and decreased mtDNA copy number were removed by the quercetin. Moreover, quercetin upregulated the Nrf2/ HO-1 axis, SOD, and CAT activity, and downregulated MDA levels in H/R treated CAECs, while knockdown Nrf2 reversed the protection of quercetin against H/R-induced oxidative stress, mitochondrial damage, and apoptosis. Quercetin protects CAECs against H/R-induced mitochondrial apoptosis via the Nrf2/HO-1 axis, which innovatively suggests the therapeutic potential of quercetin for coronary heart disease (CHD) treatment.

MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats.

Objective: Our previous studies established that microRNA (miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) alleviates acute lung injury (ALI). This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy. Methods: Exosomes were isolated from hUC-MSCs. Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor. Hematoxylin-eosin staining evaluated inflammatory injury. Enzyme-linked immunosorbnent assay measured lipopolysaccharide (LPS), tumor necrosis factor-α, and interleukin-1ß levels. qRT-PCR detected miR-451 and tuberous sclerosis complex 1 (TSC1) expressions. The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system. Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin (mTOR) pathway and autophagy. Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level. Results: hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy. MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1. Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages. Silencing TSC1 activated mTOR signaling and inhibited autophagy, while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced. Conclusion: miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway, providing a potential therapeutic strategy for ALI.

Internal Capsulation Via Self-Cross-linking and π-Effects Achieves Highly Stable Perovskite Solar Cells.

Pursuing high stability becomes the core challenge in realizing the widespread application of perovskite solar cells (PerSCs). Here, a practical internal-capsulation strategy is proposed by introducing cross-linkable methacrylate analogs upon the perovskite layer, hindering ion migration and preventing lead leakage to achieve stable PerSCs. Butyl methacrylate (UMA) and benzyl methacrylate (BMA) can chemically interact with the perovskite layer, especially for the BMA dimer with significant π-interactions among the hanging benzene rings. Such configuration facilitated more compact coordination, thereby restoring the Fermi level of perovskite to a defect-free state and reducing carrier recombination losses. Moreover, by integrating the self-cross-linking and intermolecular π-effect, the application of BMA upgraded the internal capsulation from linear protection to a compact mesh-like scale. Consequently, the application of BMA not only boosted the efficiency to 25.31% but also greatly enhanced the stability of the perovskite layer, especially for water resistance and preventing lead linkage. The internal capsulation strategy upgrading from linear to mesh-like marked an innovative direction in protecting the perovskite layer, paving the way for more sustainable PerSCs in further application.

Acupuncture ameliorates synovitis in mice with collagen-induced arthritis by repressing ferroptosis via butyric acid.

It has been reported that the symptoms of rheumatoid arthritis (RA) can be ameliorated by acupuncture, an external treatment of traditional Chinese medicine. However, the immune mechanism underlying its action is elusive. Accordingly, this study investigated the role and mechanism of manual acupuncture (MA) in collagen-induced arthritis (CIA) in mice. The results demonstrated that MA or NaB treatment reduced Articular Index scores and right paw thickness and alleviated synovial inflammation and cartilage damage. MA or NaB treatment altered the content and relative abundance of short-chain fatty acids, particularly butyric and propionic acids, in feces. Additionally, MA or NaB treatment elevated SCD1, SREBP1, and GPX4 protein expression in synovial tissues and GSH-px contents in serum while decreasing ROS fluorescence intensity and MDA contents in peripheral blood. A linear correlation was found between the relative expression of SCD1 and SREBP1 in synovial tissues and the contents of propionic acids and butyric acids in feces, as well as between the contents of propionic acids and butyric acids. In summary, MA regulates butyric acids to inhibit ferroptosis, therefore suppressing inflammation in RA.

A highly elastic, moisturizing, and adhesion conductive hydrogel designed for cuffless blood pressure measurement.

Real-time monitoring of blood pressure in athletes during exercise is of great importance, however, conventional methods pose challenges in achieving portable and instantaneous measurements. While, the electrodes used in emerging wearable blood pressure monitoring instruments still have certain defects. In this study, a novel cuffless blood pressure monitoring system was developed using a self-developed polyacrylamide/trehalose/LiCl (PAM/Trehalose/LiCl) conductive hydrogel as the electrode material. The hydrogel electrode has high tensile (strain: 3568 %) and conductive properties (7.57 S/m), while also exhibiting low toughness, moisture retention, and adhesion. While ensuring the comfort of the monitoring system, it can also accurately detect strain over a wide range of deformations (GF value of up to 6.31 in the strain interval of 2000-3400 %). Finally, this system accurately extracts relevant features of PPG and ECG signals and predicts cuff-less blood pressure using the BP Transformer-XL model. The main control chip, ECG detection module, Bluetooth module, and PPG detection module are integrated, and band-pass filtering and data feature extraction techniques are combined. The study found that the average errors in systolic and diastolic readings were 2.09 mmHg and 1.57 mmHg, respectively, compared to those measured by an electronic sphygmomanometer. Therefore, this study successfully combined hydrogel electrodes with a cuffless blood pressure monitoring system to provide technical support for the development of personalized training programs for future athletes and the guarantee of long-term competitive performance.

Cobalt vanadate intertwined in carboxylated multiple-walled carbon nanotubes for simultaneous electrochemical detection of ascorbic acid, dopamine and uric acid.

Low-cost transition metal vanadate-based electrochemical sensors have attracted a lot of attention recently. A cobalt vanadate and carboxylated multi-walled carbon nanotube composite (CoV/MWCNTs-COOH) was prepared by an ultrasonic-assisted assembly method. The uniform and dense MWCNTs-COOH attached to the surface of CoV not only combines the large surface area and superior conductivity of MWCNTs-COOH with the excellent electrochemical activity of CoV, but also enhances the redox reaction between CoV/MWCNTs-COOH composite and the analyte through synergistic effect of hydrogen bonding and electrostatic interaction. The electrochemical behaviors of CoV/MWCNTs-COOH composite modified glassy carbon electrode (CoV/MWCNTs-COOH/GCE) were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The simultaneous electrochemical sensing of ascorbic acid (AA), dopamine (DA) and uric acid (UA) on CoV/MWCNTs-COOH/GCE possesses good peak current signals with well-defined peak potentials. The linear ranges of AA, DA, and UA at CoV/MWCNTs-COOH/GCE are 1.0-100.0 µM, and the limits of detection (LODs; S/N = 3) are 0.4 µM, 0.03 µM, and 0.1 µM, respectively. The practicality of the designed sensor was further confirmed by the good recoveries obtained in the simultaneous measurement of actual samples including fetal bovine serum, human serum, urine, and Vitamin C tablets. Overall, the developed electrochemical sensor shows potential therapeutic applications for simultaneous determination of AA, DA and UA in biological fluids.

Identification of Potential Key Genes for the Comorbidity of Myasthenia Gravis With Thymoma by Integrated Bioinformatics Analysis and Machine Learning.

Background: Thymoma is a key risk factor for myasthenia gravis (MG). The purpose of our study was to investigate the potential key genes responsible for MG patients with thymoma. Methods: We obtained MG and thymoma dataset from GEO database. Differentially expressed genes (DEGs) were determined and functional enrichment analyses were conducted by R packages. Weighted gene co-expression network analysis (WGCNA) was used to screen out the crucial module genes related to thymoma. Candidate genes were obtained by integrating DEGs of MG and module genes. Subsequently, we identified several candidate key genes by machine learning for diagnosing MG patients with thymoma. The nomogram and receiver operating characteristics (ROC) curves were applied to assess the diagnostic value of candidate key genes. Finally, we investigated the infiltration of immunocytes and analyzed the relationship among key genes and immune cells. Results: We obtained 337 DEGs in MG dataset and 2150 DEGs in thymoma dataset. Biological function analyses indicated that DEGs of MG and thymoma were enriched in many common pathways. Black module (containing 207 genes) analyzed by WGCNA was considered as the most correlated with thymoma. Then, 12 candidate genes were identified by intersecting with MG DEGs and thymoma module genes as potential causes of thymoma-associated MG pathogenesis. Furthermore, five candidate key genes (JAM3, MS4A4A, MS4A6A, EGR1, and FOS) were screened out through integrating least absolute shrinkage and selection operator (LASSO) regression and Random forest (RF). The nomogram and ROC curves (area under the curve from 0.833 to 0.929) suggested all five candidate key genes had high diagnostic values. Finally, we found that five key genes and immune cell infiltrations presented varying degrees of correlation. Conclusions: Our study identified five key potential pathogenic genes that predisposed thymoma to the development of MG, which provided potential diagnostic biomarkers and promising therapeutic targets for MG patients with thymoma.

Inhibiting circ_0000673 blocks the progression of colorectal cancer through downregulating CPSF6 via targeting miR-548b-3p.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers, and its progression is regulated by several factors, including circular RNA (circRNA). OBJECTIVES: The objective of this study was to determine the role, or roles, of circ_0000673 in CRC. MATERIAL AND METHODS: We used quantitative real-time polymerase chain reaction (qPCR) to detect the expression of circ_0000673, miR-548b-3p and cleavage and polyadenylation specific factor 6 (CPSF6) in DLD-1 and RKO cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine circ_0000673 roles in proliferation. Wound healing and transwell assays were used to detect cell migration and invasion abilities. Expression of CPSF6 protein and stem cell-associated proteins were examined using western blot. The putative relationship between miR-548b-3p and circ_0000673 or CPSF6 was verified with dual-luciferase reporter assay. The role of circ_0000673 in CRC was also investigated in a tumor xenograft assay in nude mice. RESULTS: Circ_0000673 expression was increased in CRC tissues and cancer cells. Silencing circ_0000673 reduced tumor cell proliferation, migration and invasion, while also decreasing cell stemness. MiR-548b-3p was found to be a target of circ_0000673, while CPSF6 was a downstream target of miR-548b-3p. The tumor-regulatory effects of si-circ_0000673, anti-miR-548b-3p and oe-CPSF6 were partially reversed by anti-miR-548b-3p, si-CPSF6 and si-circ_0000673, respectively, in rescue assays. Downregulation of circ_0000673 reduced solid tumor growth in vivo. CONCLUSIONS: Circ_0000673 inhibition reduced CPSF6 expression by targeting miR-548b-3p, thereby blocking proliferation, migration and invasion of CRC tumor cells.