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This study investigated dissolved PAHs and OCPs in Quanzhou Bay estuaries, assessed their ecological risk, and examined anthropogenic impacts on contaminant distribution. Results showed that dissolved ∑24PAH concentrations ranged from 117 to 709 ng/L (mean: 358 ng/L), with dominance of 2-ring PAHs (Naphthalene, 1-Methylnaphthalene, and 2-Methylnaphthalene). Dissolved DDT levels ranged from 0.06 to 0.49 ng/L (mean: 0.28 ng/L), while HCBz concentrations varied from 0.02 to 0.44 ng/L (mean: 0.20 ng/L). PAHs were higher in the north due to urbanization and transport, while OCPs showed higher levels in the south due to historical agricultural use. Rural areas, water bodies, and wetlands significantly influenced the behavior of PAHs according to Spearman correlation and lasso regression analyses. Quanzhou Bay was categorized as a low to medium risk area based on dispersion simulation and ecological risk assessment, highlighting implications for future sustainable development and policy planning. CAPSULE: The coupled relationship between human activities and the distribution of dissolved PAHs and OCPs in urbanized estuaries was explored using statistical methods and GIS technology, providing valuable insights into environmental processes and pollutant control policies.
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Long-term aluminum (Al) exposure increases the risk of mild cognitive impairment (MCI). The aim of the present study was to investigate the neural mechanisms of Al-induced MCI. In our study, a total of 52 individuals with occupational Al exposure >10â years were enrolled and divided into two groups: MCI (Al-MCI) and healthy controls (Al-HC). Plasma Al concentrations and Montreal Cognitive Assessment (MoCA) score were collected for all participants. And diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to examine changes of white matter (WM) and functional connectivity (FC). There was a negative correlation between MoCA score and plasma Al concentration. Compared with the Al-HC, fractional anisotropy value for the right fornix (cres)/stria terminalis (FX/ST) was higher in the Al-MCI. Furthermore, there was a difference in FC between participants with and without MCI under Al exposure. We defined the regions with differing FC as a "pathway," specifically the connectivity from the right temporal pole to the right FX/ST, then to the right sagittal stratum, and further to the right anterior cingulate and paracingulate gyri and right inferior frontal gyrus, orbital part. In summary, we believe that the observed differences in WM integrity and FC in the right FX/ST between participants with and without MCI under long-term Al exposure may represent the neural mechanisms underlying MCI induced by Al exposure.
Subject(s)
Aluminum , Cognitive Dysfunction , Diffusion Tensor Imaging , Fornix, Brain , Magnetic Resonance Imaging , Occupational Exposure , White Matter , Humans , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Male , White Matter/drug effects , White Matter/diagnostic imaging , White Matter/pathology , Female , Middle Aged , Aged , Aluminum/toxicity , Fornix, Brain/pathology , Fornix, Brain/diagnostic imaging , Fornix, Brain/drug effects , Occupational Exposure/adverse effects , Neural Pathways/drug effects , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Neural Pathways/pathologyABSTRACT
Purpose: This study aims to evaluate the predictive efficacy of the C-reactive protein/albumin ratio (CAR), a cost-effective, easily accessible, and reproducible biomarker obtained from standard blood tests, in forecasting acute kidney injury (AKI) among patients undergoing acute pancreatitis (AP). Considering that changes in the CAR are associated with AKI incidence in AP cases, this work aims to explore whether CAR can be used as the innovative, inflammation-based diagnostic marker for AKI in AP patients. Methods: The current retrospective cohort study consecutively enrolled AP patients admitted to First College of Clinical Medical Science of China Three Gorges University during the period from January 2019 to October 2023. Data were extracted systematically in electronic medical records from these hospitalized individuals, including baseline demographic and clinical characteristics. To ascertain the association of the CAR level with the development of AKI, we carried out multivariate logistic regression, adjusting for potential confounders. These confounders were initially identified through univariate regression. Furthermore, the potential effect modifiers in the relationship between CAR and AKI occurrence were explored by stratified logistic regression. Results: Totally, 1514 AP were recruited, including 257 (16.9%) with AKI. CAR was positively correlated with AKI. When adjusting for potential confounders, the AKI risk in patients in the upper CAR tertile (2.628-22.994) increased by 83% relative to those in lower tertile (0.05-0.289) (OR 1.83, 95% CI 1.13-2.96, P = 0.013). The AKI risk tended to increase according to the increasing CAR tertile (P for trend = 0.013). No significant interactions were observed among subgroups based on age, sex, BMI, admission to ICU, hypertension, DM, chronic obstructive pulmonary disease, severity of AP, etiology of AP, demand for CRRT, mechanical ventilation, and blood transfusion (all P > 0.05). Conclusion: A higher CAR is significantly related to the higher AKI incidence in AP patients in the Chinese population.
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[This corrects the article DOI: 10.3389/fcimb.2022.1021320.].
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OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.
Subject(s)
Follicle Stimulating Hormone , Luteinizing Hormone , Sex Hormone-Binding Globulin , Humans , Male , Follicle Stimulating Hormone/blood , Middle Aged , Adult , Luteinizing Hormone/blood , Risk Factors , Sex Hormone-Binding Globulin/metabolism , Sex Hormone-Binding Globulin/analysis , Estradiol/blood , Non-alcoholic Fatty Liver Disease/blood , China/epidemiology , Case-Control Studies , ROC Curve , Biomarkers/blood , Fatty Liver/blood , AgedABSTRACT
Objective: SAF-189s is a potent ALK/ROS1 inhibitor that is currently in clinical development for treating advanced ALK+/ROS1+ non-small cell lung cancer (NSCLC). Comprehensive population pharmacokinetics (PopPK) and exposure-response models were developed to evaluate the efficacy and safety of SAF-189s by integrating data from two clinical studies. Methods: The PopPK model was developed using plasma concentration data collected from patients with ALK+/ROS1+ advanced NSCLC (n = 299) and healthy subjects (n = 24). The covariates (demographics, laboratory values, subject types, and concomitant medications) were evaluated to determine their potential influence on the between-patient variability in the pharmacokinetics of SAF-189s. Individual exposure values were then used to investigate the relationships with the efficacy endpoints (overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR)) and key safety endpoints (adverse events of interest). Results: The final PopPK model of SAF-189s was described by a one-compartment model with delayed first-order absorption and time-dependent elimination by allowing the clearance to decrease stepwise over time. Age was included as a covariate for apparent clearance (CL/F), while prior anti-cancer therapy in ALK+ patients (ALKPOT) was included for apparent volume of distribution (V/F). There were no apparent exposure-response relationships for any of the efficacy endpoints at doses of 80-210 mg. The relationship between exposure and safety suggested that a higher steady-state exposure was associated with more frequent incidences of hyperglycemia and proteinuria; the 210-mg dose group was also less tolerated than the other low-dose groups. Conclusion: PopPK and exposure-response models were developed for SAF-189s, and their results demonstrate that SAF-189s exposures are at the plateau of exposure-response for efficacy. The 210-mg dose group had a significantly higher safety risk, while the 160-mg dose group was well-tolerated. Thus, 160 mg of SAF-189s once daily was selected as the recommended phase III dose for the ALK+/ROS1+ or ROS1+ NSCLC patients.
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The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.
Subject(s)
Benzylisoquinolines , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Interferon Regulatory Factor-3 , Lung Neoplasms , Membrane Proteins , Programmed Cell Death 1 Receptor , Protein Serine-Threonine Kinases , Signal Transduction , Animals , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Benzylisoquinolines/pharmacology , Benzylisoquinolines/therapeutic use , Humans , Membrane Proteins/metabolism , Interferon Regulatory Factor-3/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Mice , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Immunotherapy/methods , Female , Mice, Inbred C57BL , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Tumor Microenvironment/drug effects , Mice, Inbred BALB C , Drug SynergismABSTRACT
Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.
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Background: Many studies have pointed out that iron overload in the body is a risk factor for coronary atherosclerosis (AS), while there are also studies that show that iron deficiency is associated with coronary AS. There is still no consensus on how iron metabolism affects coronary artery disease (CAD). This study aimed to analyze the relationship between iron metabolism indexes and CAD, investigate the diagnostic value of soluble transferrin receptor (sTfR) in suspected CAD, and establish a diagnostic model. Methods: This was a retrospective study. A total of 268 people with CAD-like symptoms who underwent coronary angiography in the Department of Cardiovascular Medicine, The Second Affiliated Hospital of Anhui Medical University from September 2022 to May 2023 without other chronic diseases or related medication history were included in the study and formed a continuous series including 188 CAD patients and 80 control subjects. Each iron metabolism index was divided into a grade variable according to tertile. The comparison of CAD morbidity between the tertiles and nonlinear correlation test was conducted to investigate the relationship between iron metabolism indexes and CAD risk. We used restricted cubic spline (RCS) to plot the relationship curve between sTfR and CAD risk and to determine the sTfR value corresponding to the minimal odds, according to which we divided the total sample into the "sTfR low level" subgroup and the "sTfR high level" subgroup. Logistic regression analyses were used to establish diagnostic models in both subgroups. The diagnostic efficiency of the indexes and models was compared by receiver operating characteristic (ROC) analysis. Results: There is a "J" shape correlation between sTfR and CAD risk. Age/sTfR ratio [area under the curve (AUC) =0.690, 95% confidence interval (CI): 0.598-0.782, specificity 0.488 and sensitivity 0.842] has the best diagnostic efficiency in the "sTfR low level" subgroup. The diagnostic efficiency of sTfR (AUC =0.701, 95% CI: 0.598-0.803, specificity 0.541 and sensitivity 0.797) in the "sTfR high level" subgroup was higher than that of cardiac troponin I (cTnI) (AUC =0.674, 95% CI: 0.564-0.784, specificity 0.719 and sensitivity 0.653). The specific diagnostic methods were as follows: (I) When sTfR ≤1.087 mg/L, calculate the age/sTfR ratio, which indicates the diagnosis of CAD when the result is >58.595; (II) We can directly make a preliminary clinical diagnosis of CAD when sTfR >1.205 mg/L. Except for the above 2 cases, we can initially rule out a diagnosis of CAD. Conclusions: The iron metabolism index sTfR correlates with CAD morbidity in a "J" shape. With superior diagnostic efficacy than cTnI, sTfR can assist in diagnosing CAD in patients with CAD-like symptoms. In addition, sTfR can provide guidance for the management of body iron levels in CAD patients.
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Background: Presenilin (PSEN, PS) is essential for γ-secretase function, and mutations can disrupt amyloid-ß (Aß) production in familial Alzheimer's disease. Targeting γ-secretase is complex due to its broad involvement in physiological processes. Objective: Our aim was to create a novel knockin (KI) mouse model expressing PSEN1 D385A mutation and investigate the efficacy of a Geniposide and Ginsenoside Rg1 combination (NeuroProtect modified formula, NP-2) in restoring γ-secretase activity. Methods: Using gene manipulation, we established the PS1 D385A KI mouse model and confirmed the mutation, mRNA, and protein levels using Southern blotting, northern blotting, and western blotting, respectively. In vitro γ-secretase assay was conducted to measure γ-secretase activity, while histological analyses examined neurogenesis effects. NP-2 administration evaluated its impact on γ-secretase activity. Results: The PS1 D385A KI homozygotes displayed severe cerebral hemorrhage, postnatal lethality, developmental disorders, reduced proliferation of neural progenitor cells, and disrupted γ-secretase function. The mutation abolished PS1 protein self-shearing, leading to compromised γ-secretase activity. NP-2 intervention effectively restored γ-secretase activity in the heterozygous mice. Conclusions: PS1 D385A mutant disrupted PS1 protein self-cleaving, impairing γ-secretase activity in KI mice. NP-2 restored γ-secretase function, offering potential for novel AD treatment strategies despite the challenges posed by γ-secretase's complex role in physiological processes.
Subject(s)
Amyloid Precursor Protein Secretases , Disease Models, Animal , Ginsenosides , Mice, Transgenic , Presenilin-1 , Animals , Presenilin-1/genetics , Amyloid Precursor Protein Secretases/metabolism , Amyloid Precursor Protein Secretases/genetics , Mice , Ginsenosides/pharmacology , Gene Knock-In Techniques , Alzheimer Disease/genetics , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Mutation/genetics , Mice, Inbred C57BL , MaleABSTRACT
Solar-to-hydrogen (H2) and oxygen (O2) conversion via photocatalytic overall water splitting (OWS) holds great promise for a sustainable fuel economy, but has been challenged by the backward O2 reduction reaction (ORR) with favored proton-coupled electron transfer (PCET) dynamics. Here, we report that molecular engineering by methylation inhibits the backward ORR of molecular photocatalysts and enables efficient OWS process. As demonstrated by a benchmark sulfone-based covalent organic framework (COF) photocatalyst, the precise methylation of its O2 adsorption sites effectively blocks electron transfer and increases the barrier for hydrogen intermediate desorption that cooperatively obstructs the PCET process of ORR. Methylation also repels electrons to the neighboring photocatalytic sulfone group that promotes the forward H2 evolution. The resultant DS-COF achieves an impressive inhibition of about 70 % of the backward reaction and a three-fold enhancement of the OWS performance with a H2 evolution rate of 124.7â µmol h-1 g-1, ranking among the highest reported for organic-based photocatalysts. This work provides insights for engineering photocatalysts at the molecular level for efficient solar-to-fuel conversion.
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A variety of strategies have been developed to enhance the cycling stability of Si-based anodes in lithium-ion batteries. Although significant progress has been made in enhancing the cycling stability of Si-based anodes, the low initial Coulombic efficiency (ICE) remains a significant challenge to their commercial application. Herein, pitch-based carbon (C) coated Si nanoparticles (NPs) were wrapped by graphene (G) to obtain Si@C/G composite with a small specific surface area of 11.3 m2g-1, resulting in a high ICE of 91.2% at 500 mA g-1. Moreover, the integrated utilization of graphene and soft carbon derived from the low-cost petroleum pitch strongly promotes the electrical conductivity, structure stability, and reaction kinetics of Si NPs. Consequently, the synthesized Si@C/G with a Si loading of 54.7% delivers large reversible capacity (1191 mAh g-1at 500 mA g-1), long cycle life over 200 cycles (a capacity retention of 87.1%), and superior rate capability (952 mAh g-1at 1500 mA g-1). When coupled with a homemade LiNi0.8Co0.1Mn0.1O2(NCM811) cathode in a full cell, it exhibits a promising cycling stability for 200 cycles. This work presents an innovative approach for the manufacture of Si-based anode materials with commercial application.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. METHODS: A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. RESULTS: The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. CONCLUSION: Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.
Subject(s)
Gene Expression Regulation, Neoplastic , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Male , Survival Rate , FemaleABSTRACT
Chronic wounds are characterized with excessive biofluid and persistent infection. Therefore, there is an urgent desire to develop a multifunctional wound dressing that can meet the extreme requirements including effective antibacterial and powerful wound microenvironment regulation and protection function to promote wounds heal quickly. In this study, a multifunctional composite dressing (HA-AMP/SF/Alg/Rb-BG-AIEgens) was synthesized by combining a mesoporous bioactive glass framework loaded with AIEgens (Rb-BG-AIEgens) with cross-linked antimicrobial peptide grafted hyaluronic acid (HA-AMP), sodium alginate (Alg), and silk fibroin (SF). It is important to note that the Rb-BG-AIEgens can achieve real-time and sensitive bacterial detection. HA-AMP can achieve broad spectrum antibacterial and avoid the residue of drug-resistant bacteria. The HA-AMP/SF/Alg/Rb-BG-AIEgens dressing can up-regulate related proliferative proteins, thereby promoting regeneration of tissue and the rapid healing of chronic wounds. With good biocompatibility and antibacterial ability, HA-AMP/SF/Alg/Rb-BG-AIEgens dressing has great potential to become a next generation wound dressing for clinical biological fluid management and chronic bacterial infection treatment.
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Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100â¯mm, 2.7⯵m analytical column. System flow rate was optimised to 2.0â¯mL/min with 40×10-6/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1â¯% o-phthaldialdehyde, 0.8â¯% 2-mercaptoethanol, 7.13â¯% methanol, and 1.81â¯% sodium tetraborate. The pre-column derivatisation program mixed 0.1⯵L sample with 25⯵L OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15â¯min, with L-aspartic acid eluted at 0.96â¯min and internal standard at 4.7â¯min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15â¯%, 3.05â¯%, and 3.09â¯% (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41â¯%, -1.37±3.04â¯%, and -3.03±3.02â¯% (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.
Subject(s)
Asparaginase , Drug Monitoring , Polyethylene Glycols , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Asparaginase/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Humans , Chromatography, High Pressure Liquid/methods , Child , Polyethylene Glycols/chemistry , Drug Monitoring/methods , Antineoplastic Agents/blood , Reproducibility of Results , Chromatography, Reverse-Phase/methods , CalibrationABSTRACT
Non-small cell lung cancer (NSCLC) is the primary inducer of cancer-related death worldwide. Asiaticoside (ATS) is a triterpenoid saponin that has been indicated to possess an antitumor activity in several malignancies. Nonetheless, its detailed functions in NSCLC remain unclarified. In this study, NSCLC cells were exposed to various doses of ATS. Functional experiments were employed to estimate the ATS effect on NSCLC cell behaviors. Western blotting was implemented for protein expression evaluation. A xenograft mouse model was established to assess the ATS effect on NSCLC in vivo. The results showed that ATS restrained NSCLC cell proliferation, cell cycle progression, migration, and invasiveness. ATS reversed TGF-ß-induced promotion in epithelial-mesenchymal transition (EMT). Mechanistically, ATS inhibited Wnt/ß-catenin signaling in NSCLC. Upregulating ß-catenin restored ATS-mediated suppression of NSCLC cell aggressiveness. Moreover, ATS administration repressed tumorigenesis in tumor-bearing mice. In conclusion, ATS represses growth and metastasis in NSCLC by blocking EMT via the inhibition of Wnt/ß-catenin signaling.
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OBJECTIVE: High-risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild-type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high-risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. METHODS: We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high-risk molecular markers were tested, and various habitat models and whole-tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high-risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank-sum test was employed to explore the correlation between habitat quantitative features (intra-tumor heterogeneity scoreï¼ITH score) and heterogeneity, as well as high-risk molecular subtypes. RESULTS: The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high-risk and non-high-risk molecular subtypes. INTERPRETATION: The habitat model based on DKI is an ideal means for preoperatively predicting high-risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.
Subject(s)
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Female , Male , Middle Aged , Glioma/diagnostic imaging , Glioma/genetics , Adult , Retrospective Studies , Aged , Diffusion Tensor Imaging/methods , Young AdultABSTRACT
BACKGROUND: To date, there is no effective treatment for Alzheimer's disease (AD), a progressive neurodegenerative disorder that is increasing in prevalence worldwide. The objective of this review was to summarize the core targets and signaling pathways involved in acupuncture treatment for AD. METHODS: We reviewed numerous signaling pathways, including mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase-protein kinase B (PI3 K/Akt), adenosine monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), nuclear factor (NF)-kB, p53, Wnt, nitric oxide (NO), Janus kinase / signal transducer and activator of transcription (JAK/ STAT), RhoA/ROCK (Rho-associated protein kinase) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) / cyclic adenosine monophosphate-response element-binding protein (CREB). The relevant data were obtained from PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases. RESULTS: In summary, the effects of acupuncture are mediated by multiple targets and pathways. Furthermore, acupuncture can improve pathological changes associated with AD (such as abnormal deposition of amyloid (A)ß, tau hyperphosphorylation, synaptic dysfunction and neuronal apoptosis) through multiple signaling pathways. CONCLUSION: Overall, our findings provide a basis for future research into the effects of acupuncture on AD.
Subject(s)
Acupuncture Therapy , Alzheimer Disease , Signal Transduction , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Humans , AnimalsABSTRACT
Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.
Subject(s)
Aluminum , Cognitive Dysfunction , Gray Matter , Magnetic Resonance Imaging , Occupational Exposure , White Matter , Humans , Gray Matter/drug effects , Gray Matter/diagnostic imaging , Gray Matter/pathology , White Matter/drug effects , White Matter/diagnostic imaging , White Matter/pathology , Cognitive Dysfunction/chemically induced , Male , Middle Aged , Female , Aluminum/toxicity , Occupational Exposure/adverse effects , Adult , Nerve Net/drug effects , Nerve Net/diagnostic imaging , Nerve Net/pathology , Nerve Net/physiopathology , AgedABSTRACT
BACKGROUND: Identifying the associations between BRAFV600E mutation, the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and clinicopathological characteristics could assist in making appropriate treatment strategies for pediatric patients with papillary thyroid carcinoma. OBJECTIVE: To retrospectively assess the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma. MATERIALS AND METHODS: Between May 2013 and May 2023, pediatric patients with papillary thyroid carcinoma who underwent thyroidectomy were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to determine the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics. The diagnostic performance of TI-RADS to predict BRAFV600E mutation was assessed. RESULTS: The BRAFV600E mutation was found in 59.1% (39/66) of pediatric patients with papillary thyroid carcinoma. Multivariate analyses showed that hypoechoic/very hypoechoic [odds ratio (OR) = 8.48; 95% confidence interval (CI) = 1.48-48.74); P-value = 0.02] and punctate echogenic foci (OR = 24.3; 95% CI = 3.80-155.84; P-value = 0.001) were independent factors associated with BRAFV600E mutation. In addition, BRAFV600E mutation was significantly associated with TI-RADS 5 (OR = 12.61; 95% CI = 1.28-124.49; P-value = 0.03). There were no associations between BRAFV600E mutation and nodule size, composition, shape, margin, cervical lymph node metastasis, or Hashimoto's thyroiditis (P-value > 0.05). Combined with hypoechoic/very hypoechoic and punctate echogenic foci, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.7%, 85.2%, 89.7%, 85.2%, and 87.9%, respectively. CONCLUSIONS: Hypoechoic/very hypoechoic, punctate echogenic foci, and TI-RADS 5 are independently associated with BRAFV600E mutation in pediatric patients with papillary thyroid carcinoma.