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In this paper, we propose the design of extending collimators aimed at reducing the radiation dose received by patients with normal tissues and protecting organs at risk in Boron Neutron Capture Therapy (BNCT). Three types of extended collimators are studied: Type 1, which is a traditional design; Type 2, which is built upon Type 1 by incorporating additional polyethylene material containing lithium fluoride (PE(LiF)); Type 3, which adds lead (Pb) to Type 1. We evaluated the dose distribution characteristics of the above-extended collimators using Monte Carlo methods simulations under different configurations: in air, in a homogeneous phantom, and a humanoid phantom model. Firstly, the neutron and gamma-ray fluxes at the collimator outlet of the three designs showed no significant changes, thus it can be expected that their therapeutic effects on tumors will be similar. Then, the dose distribution outside the irradiation field was studied. The results showed that, compared with Type 1, Type 2 has a maximum reduction of 57.14% in neutron leakage dose, and Type 3 has a maximum reduction of 21.88% in gamma-ray leakage dose. This will help to reduce the radiation dose to the local skin. Finally, the doses of different organs were simulated. The results showed that the neutron dose of Type 2 was relatively low, especially for the skin, thyroid, spinal cord, and left lung, with the neutron dose reduced by approximately 20.34%, 16.18%, 26.05%, and 18.91% respectively compared to Type 1. Type 3 collimator benefits in reducing gamma-ray dose for the thyroid, esophagus, and left lung organs, with gamma-ray dose reductions of around 10.81%, 9.45%, and 10.42% respectively. This indicates that attaching PE(LiF) or Pb materials to a standard collimator can suppress the dose distribution of patient organs, which can provide valuable insights for the design of extended collimators in BNCT., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This study aims to establish phantom-solution systems suitable for estimating doses in boron neutron capture therapy (BNCT). The phantom containing three typical solutions, H 3 BO 3 , LiOH, and Gd(NO₃)₃·6H₂O with different concentrations and nuclide abundances have been studied since the nuclides 10 B, 6 Li, and 157 Gd are capable of absorbing thermal neutrons. The results indicate that all three phantom-solution systems, with suitable concentrations and nuclide abundances, effectively distinguish between the nitrogen dose and the hydrogen dose for dose measurement in BNCT., Competing Interests: Declaration of competing interest The authors of this study are responsible for its content. All authors declare that they have no competing interests. This systematic review involved only the extraction of data from other published studies, thus, there is no need for patients’ consent and ethics committee approval was not necessary., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cirsii Japonici Herba Carbonisata (Dajitan in Chinese) has been used to treat liver disorders in Asian countries. Pectolinarigenin (PEC), an abundant constituent in Dajitan, has been found to possess a wide range of biological benefits, including hepatoprotective effects. However, the effects of PEC on acetaminophen (APAP)-induced liver injury (AILI) and the underlying mechanisms have not been studied., Purposes: To explore the role and mechanisms of PEC in protecting against AILI., Study Design and Methods: The hepatoprotective benefits of PEC were studied using a mouse model and HepG2 cells. PEC was tested for its effects by injecting it intraperitoneally before APAP administration. To assess liver damage, histological and biochemical tests were performed. The levels of inflammatory factors in the liver were measured using RT-PCR and ELISA. Western blotting was used to measure the expression of a panel of key proteins involved in APAP metabolism, as well as Nrf2 and PPARα. PEC mechanisms on AILI were investigated using HepG2 cells, while the Nrf2 inhibitor (ML385) and PPARα inhibitor (GW6471) were used to validate the importance of either Nrf2 and PPARα in the hepatoprotective effects of PEC., Results: PEC treatment decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels in the liver. PEC pretreatment increased the activity of superoxide dismutase (SOD) and glutathione (GSH) while decreasing malondialdehyde production (MDA). PEC could also up-regulate two important APAP detoxification enzymes (UGT1A1 and SULT1A1). Further research revealed that PEC reduced hepatic oxidative damage and inflammation, and up-regulated APAP detoxification enzymes in hepatocytes by activating the Nrf2 and PPARα signaling pathways., Conclusions: PEC ameliorates AILI by decreasing hepatic oxidative stress and inflammation while increasing phase Ⅱ detoxification enzymes related to APAP harmless metabolism through activation of Nrf2 and PPARα signaling. Hence, PEC may serve as a promising therapeutic drug against AILI., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Oxidative stress contributes greatly to initiation and progression of liver injury. Activation of nuclear-factor erythroid 2-related factor 2 (Nrf2) has been considered as an attractive strategy for preventing and treating the oxidative damage related to liver injury. This study aimed to find an efficacious agent to activate Nrf2/HO-1 signaling pathway from clinically used therapeutic agents and to characterize the usefulness for preventing and treating CCl 4 -induced acute liver injury. For this purpose, a series of clinically used therapeutic agents were collected and their activation potentials on Nrf2 were assayed by using 293T-Nrf2-luc cell line. Among all tested therapeutic agents, midazolam was found with good Nrf2 activation effect and this agent could significantly ameliorate CCl 4 -induced damage to HepG2 cells. In vivo animal tests showed that pretreatment with midazolam reduced the liver pathological tissue damage and the serum levels of ALT and AST in CCl 4 -induced liver injury mice. Further investigations showed that midazolam could strongly up-regulate the expression of both Nrf2 and HO-1 in the mice liver, accompanied by increasing of the levels of antioxidant enzyme SOD and reducing the production of MDA, as well as reducing the pro-inflammatory cytokines (IL-6, TNF-α) secretion. Collectively, our results clearly demonstrate that midazolam can ameliorate CCl 4 -induced acute liver injury and oxidative stress via activating the Nrf2 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhu, Li, Ji, Ge and Xu.)

Purpose: To explore the value of machine learning model based on CE-MRI radiomic features in preoperative prediction of sentinel lymph node (SLN) metastasis of breast cancer., Methods: The clinical, pathological and MRI data of 177 patients with pathologically confirmed breast cancer (81 with SLN positive and 96 with SLN negative) and underwent conventional DCE-MRI before surgery in the First Affiliated Hospital of Soochow University from January 2015 to May 2021 were analyzed retrospectively. The samples were randomly divided into the training set ( n =123) and validation set ( n = 54) according to the ratio of 7:3. The radiomic features were derived from DCE-MRI phase 2 images, and 1,316 original eigenvectors are normalized by maximum and minimum normalization. The optimal feature filter and selection operator (LASSO) algorithm were used to obtain the optimal features. Five machine learning models of Support Vector Machine, Random Forest, Logistic Regression, Gradient Boosting Decision Tree, and Decision Tree were constructed based on the selected features. Radiomics signature and independent risk factors were incorporated to build a combined model. The receiver operating characteristic curve and area under the curve were used to evaluate the performance of the above models, and the accuracy, sensitivity, and specificity were calculated., Results: There is no significant difference between all clinical and histopathological variables in breast cancer patients with and without SLN metastasis (P >0.05), except tumor size and BI-RADS classification (P< 0.01). Thirteen features were obtained as optimal features for machine learning model construction. In the validation set, the AUC (0.86) of SVM was the highest among the five machine learning models. Meanwhile, the combined model showed better performance in sentinel lymph node metastasis (SLNM) prediction and achieved a higher AUC (0.88) in the validation set., Conclusions: We revealed the clinical value of machine learning models established based on CE-MRI radiomic features, providing a highly accurate, non-invasive, and convenient method for preoperative prediction of SLNM in breast cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Yang and Shen.)

Purpose: Neuroimaging studies on migraine have revealed structural and functional alterations in the hippocampus, a region involved in pain processing and stress response. This study was designed to investigate whether effective connectivity of this region is disrupted in migraine and relates to chronicity of this disease., Patients and Methods: In 39 episodic migraine (EM) patients, 17 chronic migraine (CM) patients, and 35 healthy controls, we investigated differences in the directional influences between the hippocampus and the rest of the brain by combining resting-state functional magnetic resonance imaging and Granger causality analysis (GCA), with bilateral hippocampus as seed regions. The associations between directional influences and the clinical variables were also examined., Results: Comparing each patient group to the control group, we found increased and decreased negative influence on the hippocampus exerted by the bilateral visual areas and right dorsolateral prefrontal cortex (dlPFC), respectively. The hippocampus showed increased positive influence on the right posterior insula and medial prefrontal cortex (mPFC), as well as increased negative influence on the left cerebellum in CM patients relative to EM patients and healthy controls. Furthermore, across all patients, the migraine frequency exhibited a positive and negative association with causal influence from the hippocampus to mPFC and left cerebellum, respectively., Conclusion: Migraine patients have abnormal effective connectivity between the hippocampus and multiple brain regions involved in the sensory and cognitive processing of pain. Disrupted directional influences to the hippocampus exerted by dlPFC and bilateral visual areas were common features of EM and CM patients. Directional influences from the hippocampus to mPFC and left cerebellum may be useful imaging biomarkers for assessing migraine frequency., Competing Interests: The authors declare that they have no conflicts of interest in this study., (© 2021 Zhu et al.)

Statins are a group of hydroxymethylglutaryl coenzyme A reductase inhibitors that are used in the treatment of cardiovascular diseases. However, statins have been found to be cytotoxic, and many unexpected side effects have been reported in clinical applications. The susceptibilities of different cell lines toward statins are diverse, and the mechanisms of cytotoxicity remain unknown. Therefore, the present study aimed to investigate differences in the susceptibility to and mechanisms of statin-induced cytotoxicity in two cell lines, HT-29 and A549, using a high content screening-based multiparametric toxicity assay panel. We found that the two cell types exhibited differing susceptibilities to the cytotoxic effects of the different statins. Additionally, the cytotoxicity was inconsistent between different statins in the two cell lines. Four statins with strong cytotoxicity decreased the viability of HT-29 cells via the mitochondrial pathway, as evidenced by decreased mitochondrial membrane potential, and elevated mitochondrial mass, calcium release and cell apoptosis, and reactive oxygen species. In contrast, these four statins only induced a decrease in the mitochondrial membrane potential in A549 cells. The above results provide an objective reason for future evaluations of cytotoxic differences in cell types and the underlying mechanisms of cytotoxicity in different statins, and provide a good scientific basis for further research on countermeasures against statin-induced cell injuries., (© 2021 Wiley Periodicals LLC.)

Background: This study aimed at investigating the feasibility of testing for soluble programmed death-1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in serum samples of glioma patients and to evaluate the diagnostic and prognostic value of these two soluble molecules., Methods: Serum samples collected from 70 glioma patients before surgery were designated as the pre-operative (Pre) group, samples obtained from 90 post-surgery glioblastoma patients were designated as the Post group, and samples from 20 healthy volunteers were used as controls. Peripheral blood sPD-1 and sPD-L1 levels were detected by using ELISA kits and compared among the groups. The associations of these soluble molecule levels with clinicopathological variables and tumour progression were investigated., Results: Among the three groups, the Pre group had the highest sPD-1 levels, whereas the median sPD-L1 level was significantly lower in the Post group than in the other two groups. The area under the curve (AUC) of sPD-1 (0.762) for diagnosis was similar to that of sPD-L1 (0.718). Higher serum levels of sPD-1 and sPD-L1 were present in samples of patients with more advanced brain tumours. Kaplan-Meier analysis showed that higher serum levels of sPD-1 (>11.14 pg/mL) and sPD-L1 (>63.03 pg/mL) might predict shorter progression-free survival times of glioma patients., Conclusions: This study showed that sPD-1 and sPD-L1 might be promising predictive biomarkers for the diagnosis and prognosis of glioma patients., Competing Interests: Conflict of Interest: The authors stated that they have no conflicts of interest regarding the publication of this article., (2020 Shujun Liu, Yadi Zhu, Chenxi Zhang, Jiajia Liu, Hong Lv, Guojun Zhang, Xixiong Kang, published by CEON/CEES.)

Human carboxylesterase 2 (hCE2), one of the most principal drug-metabolizing enzymes, catalyzes the hydrolysis of a variety of endogenous esters, anticancer agents, and environmental toxicants. The significant roles of hCE2 in both endobiotic and xenobiotic metabolism sparked great interest in the discovery and development of efficacious and selective inhibitors. However, the safe and effective inhibitors of hCE2 are scarce, due to the lack of efficient screening and evaluation systems for complex biological systems. To offer a solution to this problem, a high-content analysis (HCA)-based cell imaging and multiparametric assay method was constructed for evaluating the inhibitory effect and safety of hCE2 inhibitors in living cell system. In this study, we first established a cell imaging-based method for identifying hCE2 inhibitors at the living cell level with hCE2 fluorescent probe NCEN. Meanwhile, two nuclear probes, Hoechst 33342 and PI, were integrated to evaluate the potential cytotoxicity of compounds simultaneously. Then, the accuracy of the HCA-based method was verified by the LC-FD-based method with a positive inhibitor BNPP, and the results showed that the HCA-based method exhibited excellent precision, robustness, and reliability. Finally, the newly established HCA-based multiparametric assay panel was successfully applied to re-evaluate a series of reported hCE2 inhibitors in living cells. In summary, the HCA-based multiparametric method could serve as an efficient tool for the accuracy measurement inhibitory effect and cytotoxicity of compounds against hCE2 in living cell system. Graphical abstract.

Background: Soluble PD-L1 (sPD-L1) in the circulation has been documented to activate global immunosuppression and is considered a predictor of negative clinical outcomes in several malignances. However, the clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear. Objective: The aim of this study was to detect the correlations of sPD-L1 with clinical features in brain tumors and assess the diagnostic value of this protein in gliomas. Methods: Serum samples were obtained from 73 patients with glioma, 20 patients with meningioma, and 49 healthy controls (HCs) in this study. In total, 31 CSF samples were collected from the matched glioma patients, and seven samples were collected from the matched meningioma patients. The expression of serum sPD-L1 in the glioma cohort was followed for 20 days after surgery to examine the kinetics in the circulation. Inflammatory markers were evaluated based on preoperative blood parameters. The sPD-L1 levels in the serum and CSF were determined by enzyme-linked immunosorbent assay (ELISA). The logistic regression model was used to assess the independent associations of sPD-L1 with gliomas, including high-grade gliomas. Results: Serum and CSF levels of sPD-L1 were significantly elevated in patients with gliomas compared to those with meningiomas and HCs. Additionally, increased levels of sPD-L1 were observed in relatively advanced tumors. sPD-L1 overexpression in the CSF appears to be more representative of aggressive tumor features than overexpression in the serum. For glioma diagnosis, both serum and CSF sPD-L1 showed significant value in the diagnosis and stratification of glioma, and the best diagnostic performance was obtained with serum sPD-L1 rather than blood-based inflammatory markers. In addition, a descending trend in the level of serum sPD-L1 was observed in postoperative patients. Conclusion: In gliomas, elevated circulating and CSF sPD-L1 levels are associated with aggressive biological activities. The results of the current study suggest that sPD-L1 is a promising biomarker for gliomas that can be used in clinical practice., (Copyright © 2020 Liu, Zhu, Zhang, Meng, Sun, Zhang, Fan and Kang.)