bluuebunny/crossref_metadata_2025 huggingface dataset:
Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes
Authors: Wu Xuangao , Park Sunmin
Published: November 2022

The role of gut microbes has been suggested in type 2 diabetes (T2DM) risk. However, their results remain controversial. We hypothesized that Asians with T2DM had different fecal bacterial compositions, co-abundance networks, and metagenome functions compared to healthy individuals, according to enterotypes. This hypothesis was examined using the combined gut microbiota data from human fecal samples from previous studies. The human fecal bacterial FASTA/Q files from 36 different T2DM studies in Asians were combined (healthy, n = 3378; T2DM, n = 551), and operational taxonomic units (OTUs) and their counts were obtained using qiime2 tools. In the machine learning approaches, fecal bacteria rich in T2DM were found. They were separated into two enterotypes, Lachnospiraceae (ET-L) and Prevotellaceae (ET-P). The Shannon and Chao1 indices, representing α-diversity, were significantly lower in the T2DM group compared to the healthy group in ET-L (p < 0.05) but not in ET-P. In the Shapley additive explanations analysis of ET-L, Escherichia fergusonii, Collinsella aerofaciens, Streptococcus vestibularis, and Bifidobacterium longum were higher (p < 0.001), while Phocaeicola vulgatus, Bacteroides uniformis, and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group (p < 0.00005). In ET-P, Escherichia fergusonii, Megasphaera elsdenii, and Oscillibacter valericigenes were higher, and Bacteroides koreensis and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group. In ET-L and ET-P, bacteria in the healthy and T2DM groups positively interacted with each other within each group (p < 0.0001) but negatively interacted between the T2DM and healthy groups in the network analysis (p < 0.0001). In the metagenome functions of the fecal bacteria, the gluconeogenesis, glycolysis, and amino acid metabolism pathways were higher, whereas insulin signaling and adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling pathways were lower in the T2DM group than in the healthy group for both enterotypes (p < 0.00005). In conclusion, Asians with T2DM exhibited gut dysbiosis, potentially linked to intestinal permeability and the enteric vagus nervous system.
Identification of Resting-State Network Functional Connectivity and Brain Structural Signatures in Fibromyalgia Using a Machine Learning Approach
Authors: Thanh Nhu Nguyen , Chen David Yen-Ting , Kang Jiunn-Horng
Published: November 2022

Abnormal resting-state functional connectivity (rs-FC) and brain structure have emerged as pathological hallmarks of fibromyalgia (FM). This study investigated and compared the accuracy of network rs-FC and brain structural features in identifying FM with a machine learning (ML) approach. Twenty-six FM patients and thirty healthy controls were recruited. Clinical presentation was measured by questionnaires. After MRI acquisitions, network rs-FC z-score and network-based gray matter volume matrices were exacted and preprocessed. The performance of feature selection and classification methods was measured. Correlation analyses between predictive features in final models and clinical data were performed. The combination of the recursive feature elimination (RFE) selection method and support vector machine (rs-FC data) or logistic regression (structural data), after permutation importance feature selection, showed high performance in distinguishing FM patients from pain-free controls, in which the rs-FC ML model outperformed the structural ML model (accuracy: 0.91 vs. 0.86, AUC: 0.93 vs. 0.88). The combined rs-FC and structural ML model showed the best performance (accuracy: 0.95, AUC: 0.95). Additionally, several rs-FC features in the final ML model correlated with FM’s clinical data. In conclusion, ML models based on rs-FC and brain structural MRI features could effectively differentiate FM patients from pain-free subjects.
Cardiovascular Magnetic Resonance Imaging-Based Right Atrial Strain Analysis of Cardiac Amyloidosis
Authors: Eckstein Jan , Sciacca Vanessa , Körperich Hermann , Paluszkiewicz Lech , Valdés Elena Weise , Burchert Wolfgang , Gerçek Muhammed , Farr Martin , Sommer Philipp , Sohns Christian , Piran Misagh
Published: November 2022

Background: Cardiac amyloidosis (CA) manifests in a hypertrophic phenotype with a poor prognosis, making differentiation from hypertrophic cardiomyopathy (HCM) challenging and delaying early treatment. The extent to which magnetic resonance imaging (MRI) quantifies the right atrial strain (RAS) and strain rate (RASR), providing valuable diagnostic information, is not yet clinically established. Aims: This study assesses diagnostic differences in the longitudinal RAS and RASR between CA and HCM patients, control subjects (CTRL) and CA subtypes in addition to the impact of atrial fibrillation (AF) on the right atrial function in CA patients. The RAS and RASR of tricuspid regurgitation (TR) patients are used to assess the potential for diagnostic overlap. Methods: RAS and RASR quantification was conducted via MRI feature-tracking for biopsy-confirmed CA patients with subtypes identified. Strain parameters were compared for CTRL, HCM and TR patients. Post hoc testing identified intergroup differences. Results: In total, 41 CA patients were compared to 47 CTRL, 20 HCM and 31 TR patients. Reservoir (R), conduit and booster RAS and RASRs allow for significant differentiation (p < 0.001) between CA and HCM patients (R: 10.6 ± 14.3% vs. R: 33.5 ± 16.3%) and CTRL (R: 44.6 ± 15.7%). Booster and reservoir RAS and RASRs qualified as reliable diagnostic tests (AUC > 0.8). CA patients with AF, in contrast to sinus rhythm, demonstrated a significantly impaired reservoir RAS and RASR and booster RASR. The discriminative power of RAS for CA vs. TR was insufficient (R: 10.6% ± 14.3% vs. 7.0% ± 6.0%, p = 0.069). Differentiation between 21 transthyretin and 20 light-chain amyloidosis subtypes was not achievable (R: 0.7% ± 1.0% vs. 0.7% ± 1.0%, p = 0.827). Conclusion: The MRI-derived RAS and RASR are impaired in CA patients and may support noninvasive differentiation between CA, HCM and CTRL.
Dual-Wavelength Fluorescence Polarization Immunoassay for Simultaneous Detection of Sulfonamides and Antibacterial Synergists in Milk
Authors: Duan Changfei , Zhang Yingjie , Li Peipei , Li Qiang , Yu Wenbo , Wen Kai , Eremin Sergei A. , Shen Jianzhong , Yu Xuezhi , Wang Zhanhui
Published: November 2022

Combinations of sulfonamides (SAs) and antibacterial synergists (ASGs) are frequently used for treating infectious diseases and promoting growth for animals, which cause potential hazards to food safety and human health. To realize the simultaneous detection of SAs and ASGs in food, a homogeneous and high-throughput screening dual-wavelength fluorescence polarization immunoassay (DWFPIA) was developed. In this study, three SAs tracers and three ASGs tracers were synthesized by fluoresceins with different linkers and paired with their corresponding monoclonal antibodies (mAbs), respectively. To achieve a high sensitivity and broad specificity, the combination of tracers SADMPM-HDF with the longest linker paring mAb 10E6 for SAs and tracer HaptenA-DSCA paring mAb 9C9 for ASGs were chosen for the development of DWFPIA, achieving surprising IC50 values for 23 SAs below 100 μg L−1 and 5 ASGs below 50 μg L−1. The accuracy of DWFPIA was applied in real milk samples by typical sulfamethazine (SMZ) and trimethoprim (TMP), with recoveries of 81.7–97.2% and 78.6–103.6%, and coefficient of variations (CVs) below 18.9%, which could be completed within 15 min, including sample pretreatment. We firstly developed a simultaneous screening DWFPIA, covering all of the SAs and ASGs used in clinic and providing a great application potential in food safety analysis.
Electrochemical Immunosensor for Early Detection of β-Amyloid Alzheimer’s Disease Biomarker Based on Aligned Carbon Nanotubes Gold Nanocomposites
Authors: Ranjan Pushpesh , Khan Raju
Published: November 2022

Beta-amyloid (βA) peptides accompanying the physiological change in brain induce Alzheimer’s disease. In this work, a highly sensitive electrochemical (EC) immunosensor platform has been developed for the quantitative detection of βA peptides, using the gold nanoparticle functionalized chitosan-aligned carbon nanotube (CS-aCNT-Au) nanocomposites on glassy carbon electrodes (GCE). The immunosensor has been fabricated by immobilization of the anti-βA antibody upon CS-aCNT-Au/GCE. In the CS-aCNT nanocomposite, CS has high biocompatibility. Hydroxy and amine functionalities favor the antibody immobilization and prevent the leaching of nanocomposites of the modified electrode due to the adhesive environment. Moreover, aCNT offers high conductivity, stability, and a large surface area (the calculated effective surface area of the CS-aCNT/GCE is 8.594 × 10−2 cm2). However, the incorporation of AuNPs further enhances the conductivity of the CS-aCNT-Au nanocomposite based on differential pulse voltammetry (DPV) results, and also improves the effective surface area (9.735 × 10−2 cm2). The surface morphology and electrochemical studies of the nanocomposite, as well as its modifications by the anti-βA antibody and BSA, were carried out through field emission scanning electron microscope (FESEM), cyclic voltammetry (CV), and DPV. The quantitative immunosensing of the βA in phosphate-buffered saline (PBS) solution is accomplished via DPV, which reveals that the immunosensor has a high sensitivity of 157.60 µA pg−1 mL cm−2 and a broad detection range of 10.0 pg mL−1–100.0 µg mL−1, with a limit of detection (LOD) of 0.87 pg mL−1. Subsequently, we detected the spiked βA in diluted serum with a linear detection range of 10.0 pg mL−1–1.0 ng mL−1 and LOD of 0.95 pg mL−1. Moreover, a selectivity study exhibited a high affinity of immunosensors towards βA. Thus, we propose that this highly efficient immunosensor can potentially be applied for the point-of-care (POC) sensing of βA in clinical samples.
Flash Characterization of Smartphones Used in Point-of-Care Diagnostics
Authors: Vu Binh V. , Lei Rongwei , Mohan Chandra , Kourentzi Katerina , Willson Richard C.
Published: November 2022

Rapidly growing interest in smartphone cameras as the basis of point-of-need diagnostic and bioanalytical technologies increases the importance of quantitative characterization of phone optical performance under real-world operating conditions. In the context of our development of lateral-flow immunoassays based on phosphorescent nanoparticles, we have developed a suite of tools for characterizing the temporal and spectral profiles of smartphone torch and flash emissions, and their dependence on phone power state. In this work, these tools are described and documented to make them easily available to others, and demonstrated by application to characterization of Apple iPhone 5s, iPhone 6s, iPhone 8, iPhone XR, and Samsung Note8 flash performance as a function of time and wavelength, at a variety of power settings. Flash and torch intensity and duration vary with phone state and among phone models. Flash has high variability when the battery charge is below 10%, thus, smartphone-based Point-of-Care (POC) tests should only be performed at a battery level of at least 15%. Some output variations could substantially affect the results of assays that rely on the smartphone flash.
A Label-Free Gold Nanoparticles-Based Optical Aptasensor for the Detection of Retinol Binding Protein 4
Authors: Moabelo Koena L. , Lerga Teresa M. , Jauset-Rubio Miriam , Sibuyi Nicole R. S. , O’Sullivan Ciara K. , Meyer Mervin , Madiehe Abram M.
Published: November 2022

Retinol-binding protein 4 (RBP4) has been implicated in insulin resistance in rodents and humans with obesity and T2DM, making it a potential biomarker for the early diagnosis of T2DM. However, diagnostic tools for low-level detection of RBP4 are still lagging behind. Therefore, there is an urgent need for the development of T2DM diagnostics that are rapid, cost-effective and that can be used at the point-of-care (POC). Recently, nano-enabled biosensors integrating highly selective optical detection techniques and specificity of aptamers have been widely developed for the rapid detection of various targets. This study reports on the development of a rapid gold nanoparticles (AuNPs)-based aptasensor for the detection of RBP4. The retinol-binding protein aptamer (RBP-A) is adsorbed on the surface of the AuNPs through van der Waals and hydrophobic interactions, stabilizing the AuNPs against sodium chloride (NaCl)-induced aggregation. Upon the addition of RBP4, the RBP-A binds to RBP4 and detaches from the surface of the AuNPs, leaving the AuNPs unprotected. Addition of NaCl causes aggregation of AuNPs, leading to a visible colour change of the AuNPs solution from ruby red to purple/blue. The test result was available within 5 min and the assay had a limit of detection of 90.76 ± 2.81 nM. This study demonstrates the successful development of a simple yet effective, specific, and colorimetric rapid assay for RBP4 detection.
Nano-Engineered Surface Comprising Metallic Dendrites for Biomolecular Analysis in Clinical Perspective
Authors: Kumari Rohini , Dkhar Daphika S. , Mahapatra Supratim , Divya  , Singh Surinder P. , Chandra Pranjal
Published: November 2022

Metallic dendrites, a class of three-dimensional nanostructured materials, have drawn a lot of interests in the recent years because of their interesting hierarchical structures and distinctive features. They are a hierarchical self-assembled array of primary, secondary, and terminal branches with a plethora of pointed ends, ridges, and edges. These features provide them with larger active surface areas. Due to their enormous active areas, the catalytic activity and conductivity of these nanostructures are higher as compared to other nanomaterials; therefore, they are increasingly used in the fabrication of sensors. This review begins with the properties and various synthetic approaches of nanodendrites. The primary goal of this review is to summarize various nanodendrites-engineered biosensors for monitoring of small molecules, macromolecules, metal ions, and cells in a wide variety of real matrices. Finally, to enlighten future research, the limitations and future potential of these newly discovered materials are discussed.
Data-Driven Based Prediction of the Energy Consumption of Residential Buildings in Oshawa
Authors: Lin Yaolin , Liu Jingye , Gabriel Kamiel , Yang Wei , Li Chun-Qing
Published: November 2022

Buildings consume about 40% of the global energy. Building energy consumption is affected by multiple factors, including building physical properties, performance of the mechanical system, and occupants’ activities. The prediction of building energy consumption is very complicated in actual practice. Accurate and fast prediction of the building energy consumption is very important in building design optimization and sustainable energy development. This paper evaluates 24 energy consumption models for 83 houses in Oshawa, Canada. The energy consumption, social and demographic information of the occupants, and the physical properties of the houses were collected through smart metering, a phone survey, and an energy audit. A total of 63 variables were determined, and based on the variable importance, three groups with different numbers of variables were selected, i.e., 26, 12, and 6 for electricity consumption; and 26, 13, and 6 for gas consumption. A total of eight data-driven algorithms, namely Multiple Linear Regression (MLR), Stepwise Regression (SR), Support Vector Machine (SVM), Backpropagation Neural Network (BPNN), Radial Basis Function Neural Network (RBFN), Classification and Regression Tree (CART), Chi-Square Automatic Interaction Detector (CHAID), and Exhaustive CHAID (ECHAID), were used to develop energy prediction models. The results show that the BPNN model has the best accuracies in predicting both the annual electricity consumption and gas consumption, with mean absolute percentage errors (MAPEs) of 0.94% and 0.94% for training and validation data for electricity consumption, and 2.63% and 0.16% for gas consumption, respectively.
Evaluation and Optimization of Daylighting in Heritage Buildings: A Case-Study at High Latitudes
Authors: Piraei Farimah , Matusiak Barbara , Lo Verso Valerio R. M.
Published: November 2022

Transforming historical listed buildings into workplaces is a serious challenge, particularly for buildings with relatively small windows in the façades, which determine scarce daylighting indoors. This paper studied how daylighting can be significantly increased in a case-study historical building through rooflighting systems, as the façade cannot be modified. The case-study was a historic and iconic warehouse built-in 1681 in Trondheim, Norway. The optimized configuration was analyzed in terms of daylight amount and view analysis, according to EN 17037 and to LEED v4.1 protocol. A critical evaluation of the actual applicability of the optimized Scenario in the real building was carried out along with the constructors. A 3D model was built in Rhinoceros, and daylighting simulations of the base-case (the building in the existing configuration) and for 6 alternative Scenarios were run through Climate Studio. The following metrics were calculated: Daylight Factor (DF), Spatial Daylight Autonomy (sDA), Annual Sunlight Exposure (ASE), and views. An optimized configuration was eventually identified through the Galapagos component in Grasshopper, with an average DF value of 2.7% (against 0.9% in the base-case configuration), higher than the target DFm of 2.4% for Norway), and a sDA value of 50.2% (14.2% in base-case configuration).
Lipocalin 2 Reduces MET Levels by Inhibiting MEK/ERK Signaling to Inhibit Nasopharyngeal Carcinoma Cell Migration
Authors: Li Ju-Pi , Lin Chiao-Wen , Huang Cheng-Chen , Lu Yen-Ting , Ho Yu-Ting , Yang Shun-Fa , Hsin Chung-Han
Published: November 2022

Nasopharyngeal carcinoma (NPC) is the most common cancer that occurs in the nasopharynx, and it is difficult to detect early. The main cause of death of NPC patients is cancer metastasis. Lipocalin 2 (LCN2) has been shown to be involved in a variety of carcinogenesis processes. Here, we aimed to study the role of LCN2 in NPC cells and determine its underlying mechanism. We found that LCN2 was expressed differently in NPC cell lines, namely HONE-1, NPC-39, and NPC-BM. The down-regulation of LCN2 levels by siRNA targeting LCN2 (siLCN2) increased cell migration and invasion in HONE-1 cells, while the up-regulation of LCN2 levels by transfection with the LCN2 expression plasmid decreased cell migration and invasion in NPC-BM cells. Furthermore, LCN2 levels negatively regulated the phosphorylation of MEK/ERK pathways. The treatment of the specific MEK/ERK inhibitor, U0126, reduced cell migration in HONE-1 cells, whereas the treatment of tBHQ, an ERK activator, enhanced cell migration in NPC-BM cells. Based on the bioinformatics data, there was a moderately negative correlation between LCN2 and MET in metastatic NPC tissues (r = −0.5946, p = 0.0022). Indeed, the manipulation of LCN2 levels negatively regulated MET levels in these NPC cells. The treatment of U0126 reduced siLCN2-increased MET levels, while the treatment of tBHQ enhanced LCN2-enhanced MET levels. Interestingly, the down-regulation of MET levels by siMET further decreased siLCN2-enhanced MET levels and cell migration. Therefore, LCN2 inhibits NPC cell migration by reducing MET levels through MEK/ERK signaling.
How We Treat Localized Rectal Cancer—An Institutional Paradigm for Total Neoadjuvant Therapy
Authors: Roeder Falk , Gerum Sabine , Hecht Stefan , Huemer Florian , Jäger Tarkan , Kaufmann Reinhard , Klieser Eckhard , Koch Oliver Owen , Neureiter Daniel , Emmanuel Klaus , Sedlmayer Felix , Greil Richard , Weiss Lukas
Published: November 2022

Total neoadjuvant therapy (TNT)—the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery—may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians—without any claim to general validity.
Tat-hspb1 Suppresses Clear Cell Renal Cell Carcinoma (ccRCC) Growth via Lysosomal Membrane Permeabilization
Authors: Zhang Lin , Jin Guang-Zhi , Li Dong
Published: November 2022

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, of which the incidence is increasing worldwide with a high mortality rate. Bioactive peptides are considered a significant class of natural medicines. We applied mass spectrometry-based peptidomic analysis to explore the peptide profile of human renal clear cell carcinoma and adjacent normal tissues. A total of 18,031 peptides were identified, of which 105 unique peptides were differentially expressed (44 were up-regulated and 61 were down-regulated in ccRCC tissues). Through bioinformatic analysis, we finally selected one peptide derived from the HSPB1 protein (amino acids 12–35 of the N-terminal region of HSPB1). Next, we fused this peptide to the HIV-Tat, generated a novel peptide named Tat-hspb1, and found that Tat-hspb1 inhibited ccRCC cells’ viability while being less cytotoxic to normal epithelial cells. Furthermore, Tat-hspb1 induced apoptosis and inhibited the proliferation and migration of ccRCC cells. Furthermore, we demonstrated that Tat-hspb1 was predominantly localized in lysosomes after entering the ccRCC cell and induced lysosomal membrane permeabilization (LMP) and the release of cathepsin D from lysosomes. Taken together, Tat-hspb1 has the potential to serve as a new anticancer drug candidate.
Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets
Authors: Qiu Yumin , Chen Yan , Agbede Oluwatobi , Eshaghi Esra , Peng Chun
Published: November 2022

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, and more than 70% of patients are diagnosed at advanced stages. Despite the application of surgery and chemotherapy, the prognosis remains poor due to the high relapse rate. It is urgent to identify novel biomarkers and develop novel therapeutic strategies for EOC. Circular RNAs (circRNAs) are a class of noncoding RNAs generated from the “back-splicing” of precursor mRNA. CircRNAs exert their functions via several mechanisms, including acting as miRNA sponges, interacting with proteins, regulating transcription, and encoding functional proteins. Recent studies have identified many circRNAs that are dysregulated in EOC and may be used as diagnostic and prognostic markers. Increasing evidence has revealed that circRNAs play a critical role in ovarian cancer progression by regulating various cellular processes, including proliferation, apoptosis, metastasis, and chemosensitivity. The circRNA-based therapy may be a novel strategy that is worth exploring in the future. Here, we provide an overview of EOC and circRNA biogenesis and functions. We then discuss the dysregulations of circRNAs in EOC and the possibility of using them as diagnostic/prognostic markers. We also summarize the role of circRNAs in regulating ovarian cancer development and speculate their potential as therapeutic targets.
Comprehensive Analysis of Cuproptosis-Related Genes in Prognosis and Immune Infiltration of Hepatocellular Carcinoma Based on Bulk and Single-Cell RNA Sequencing Data
Authors: Yang Chenglei , Guo Yanlin , Wu Zongze , Huang Juntao , Xiang Bangde
Published: November 2022

Background: Studies on prognostic potential and tumor immune microenvironment (TIME) characteristics of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are limited. Methods: A multigene signature model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The cuproptosis-related multivariate cox regression analysis and bulk RNA-seq-based immune infiltration analysis were performed. The results were verified using two cohorts. The enrichment of CRGs in T cells based on single-cell RNA sequencing (scRNA-seq) was performed. Real-time polymerase chain reaction (RT-PCR) and multiplex immunofluorescence staining were performed to verify the reliability of the conclusions. Results: A four-gene risk scoring model was constructed. Kaplan–Meier curve analysis showed that the high-risk group had a worse prognosis (p < 0.001). The time-dependent receiver operating characteristic (ROC) curve showed that the OS risk score prediction performance was good. These results were further confirmed in the validation queue. Meanwhile, the Tregs and macrophages were enriched in the cuproptosis-related TIME of HCC. Conclusions: The CRGs-based signature model could predict the prognosis of HCC. Treg and macrophages were significantly enriched in cuproptosis-related HCC, which was associated with the depletion of proliferating T cells.
JAG1 Intracellular Domain Enhances AR Expression and Signaling and Promotes Stem-like Properties in Prostate Cancer Cells
Authors: Tran Tuyen Thanh , Lee Keesook
Published: November 2022

JAG1 expression is upregulated in high-grade metastatic prostate carcinomas and associated with poor disease-free survival of patients with prostate cancer. Intriguingly, all JAG1-positive prostate carcinomas express JICD although JICD function in prostate cancer (PC) cells is poorly understood. In this study, we found that JICD overexpression increased the expression levels of AR, especially AR-Vs, in PC cell lines and significantly enhanced androgen-independent and androgen-dependent function of ARs. Interestingly, JICD overexpression upregulated the expression of the PCSC marker CD133 in PC cells as the expression of self-renewal markers; namely, NANOG and OCT3/4 increased. In addition, JICD overexpression highly increased the expression of anti-apoptotic BCL-XL protein, while it little affected the expression of apoptotic BIM protein. In 3D cell culture assays, the spheres formed by JICD-overexpressing PC subline cells (C4-2 and CWR22Rv1) were larger than those formed by control (EV) subline cells with undifferentiated morphology. Although JICD overexpression caused quiescence in cell proliferation, it activated the expression of components in PCSC-related signaling pathways, increased PC cell mobility, and promoted in vivo xenograft mouse tumorigenesis. Therefore, JICD may play a crucial role in enhancing androgen independence and promoting stem-like properties in PC cells and should be considered a novel target for CRPC and PCSC diagnostic therapy.
Effect of Opioids on Survival in Patients with Cancer
Authors: Boland Jason W.
Published: November 2022

Opioids are commonly used for pain management in patients with cancer. They have a range of unwanted effects, including some that potentially influence cancer growth. This article reviews the data assessing the effects of opioids on survival in patients with cancer. Many studies assessing this show an association between opioids and decreased survival. This effect is present even at very low doses of opioids. These studies do not assess causality, so it is not known if it is a direct effect of opioids on survival. As the control groups are not matched to the opioid group it might be that opioids are being used to control pain and patients receiving opioids have more aggressive cancers and it is the underlying cancer which is causing the decreased survival. Furthermore, although some studies allude to different opioids having different effects on survival, often all opioids are pooled in analysis. Future work needs to try to ascertain causality and differentiate between different opioids, pain, and cancer-mediated effects on survival in specific cancer types. Until then, opioids should continue to be used in patients with cancer as part of measures to optimise comfort and quality of life.
Early Coronary Artery Calcification Progression over Two Years in Breast Cancer Patients Treated with Radiation Therapy: Association with Cardiac Exposure (BACCARAT Study)
Authors: Honaryar Manoj Kumar , Allodji Rodrigue , Ferrières Jean , Panh Loïc , Locquet Médéa , Jimenez Gaelle , Lapeyre Matthieu , Camilleri Jérémy , Broggio David , de Vathaire Florent , Jacob Sophie
Published: November 2022

Background: Radiotherapy (RT) for breast cancer (BC) can induce coronary artery disease many years after RT. At an earlier stage, during the first two years after RT, we aimed to evaluate the occurrence of increased coronary artery calcium (CAC) and its association with cardiac exposure. Methods: This prospective study included 101 BC patients treated with RT without chemotherapy. Based on CAC CT scans performed before and two years after RT, the event ‘CAC progression’ was defined by an increase in overall CAC score (CAC RT+ two years—CAC before RT > 0). Dosimetry was evaluated for whole heart, left ventricle (LV), and coronary arteries. Multivariable logistic regression models were used to assess association with doses. Results: Two years after RT, 28 patients presented the event ‘CAC progression’, explained in 93% of cases by a higher CAC score in the left anterior descending coronary (LAD). A dose–response relationship was observed with LV exposure (for Dmean LV: OR = 1.15, p = 0.04). LAD exposure marginally explained increased CAC in the LAD (for D2 LV: OR =1.03, p = 0.07). Conclusion: The risk of early CAC progression may be associated with LV exposure. This progression might primarily be a consequence of CAC increase in the LAD and its exposure.
Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies
Authors: Pang Lulian , Gan Chen , Xu Jian , Jia Yingxue , Chai Jiaying , Huang Runze , Li Anlong , Ge Han , Yu Sheng , Cheng Huaidong
Published: November 2022

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibiting bone metastasis (such as bisphosphate and denosumab) alleviate bone destruction and improve the quality of life of breast cancer patients with bone metastasis. However, the prognosis of these patients remains poor, and the specific biological mechanism of bone metastasis is incompletely understood. Additional basic and clinical studies are urgently needed, to further explore the mechanism of bone metastasis and develop new therapeutic drugs. This review presents a summary of the molecular mechanisms and therapeutic strategies of bone metastasis of breast cancer, aiming to improve the quality of life and prognosis of breast cancer patients and provide a reference for future research directions.
MicroRNAs and Drug Resistance in Non-Small Cell Lung Cancer: Where Are We Now and Where Are We Going
Authors: Cuttano Roberto , Afanga Miriam Kuku , Bianchi Fabrizio
Published: November 2022

Lung cancer is the leading cause of cancer-related mortality in the world. The development of drug resistance represents a major challenge for the clinical management of patients. In the last years, microRNAs have emerged as critical modulators of anticancer therapy response. Here, we make a critical appraisal of the literature available on the role of miRNAs in the regulation of drug resistance in non-small cell lung cancer (NSCLC). We performed a comprehensive annotation of miRNAs expression profiles in chemoresistant versus sensitive NSCLC, of the drug resistance mechanisms tuned up by miRNAs, and of the relative experimental evidence in support of these. Furthermore, we described the pros and cons of experimental approaches used to investigate miRNAs in the context of therapeutic resistance, to highlight potential limitations which should be overcome to translate experimental evidence into practice ultimately improving NSCLC therapy.
Hydrodeoxygenation–Isomerization of Methyl Palmitate over SAPO-11-Supported Ni-Phosphide Catalysts
Authors: Shamanaev Ivan V. , Shamanaeva Irina A. , Parkhomchuk Ekaterina V. , Bukhtiyarova Galina A.
Published: November 2022

Ni-phosphide catalysts on SAPO-11 were studied in the hydrodeoxygenation–isomerization of methyl palmitate (C15H31COOCH3—MP). The catalysts were synthesized using temperature-programmed reduction (TPR) of a phosphate precursor ((NH4)2HPO4 and Ni(CH3CH2COO)2), TPR of a phosphite precursor (H3PO3 and Ni(OH)2), and using phosphidation of Ni/SAPO-11 by PPh3 in the liquid phase. The samples were characterized by ICP-AES chemical analysis, N2 physisorption, NH3-TPD, XRD, and TEM. First, the screening of the catalysts prepared by the TPR method was carried out in a semi-batch autoclave to determine the influence of the preparation method and conditions on one-pot HDO–isomerization (290–380 °C, 2–3 MPa). The precursor’s nature and the amount of phosphorus strongly influenced the activity of the catalysts and their surface area and acidity. Isomerization occurred only at a low P content (Ni/P = 2/1) and blocking of the SAPO-11 channels by unreduced phosphates at higher P contents did not allow us to obtain iso-alkanes. Experiments with liquid phosphidation samples in a continuous-flow reactor also showed the strong dependence of activity on phosphidation duration as well as on Ni content. The highest yield of isomerized products (66% iso-C15–16 hydrocarbons, at complete conversion of O-containing compounds, 340 °C, 2 MPa, and LHSV = 5.3 h−1) was obtained over 7% Ni2P/SAPO-11 prepared by the liquid phosphidation method.
Removal of Persistent Acid Pharmaceuticals by a Biological-Photocatalytic Sequential Process: Clofibric Acid, Diclofenac, and Indomethacin
Authors: Cruz-Carrillo María J. , Melgoza-Alemán Rosa M. , Cuevas-Arteaga Cecilia , Proal-Nájera José B.
Published: November 2022

The removal of three acid pharmaceuticals—clofibric acid (CLA), diclofenac (DCL), and indomethacin (IND)—by a biological-photocatalytic sequential system was studied. These pharmaceutical active compounds (PhACs) are considered to persist in the environment and have been found in water and sewage, producing adverse effects on the aquatic environment. For the biological process, in batch experiments, a fixed bed bioreactor and activated sludge (hybrid bioreactor), under aerobic conditions, was used as pretreatment. The pretreated effluent was exposed to a photocatalytic process employing TiO2 nanotubular films (NTF-TiO2) with the following characteristics: an internal diameter of 112 nm, a wall thickness of 26 nm, nanotube length of 15 µm, a roughness factor of 1840 points, and an anatase-rutile crystalline structure. In the hybrid bioreactor, 39% IND and 50% ACL and DCL were removed. The biological-photocatalysis sequential system achieved the degradation of up to 90% of the initial concentrations of the three acid pharmaceuticals studied. This approach appears to be a viable alternative for the treatment of these non-biodegradable effluents.
Enhancement and Mechanism of Rhodamine B Decomposition in Cavitation-Assisted Plasma Treatment Combined with Fenton Reactions
Authors: Xu Yifan , Komarov Sergey , Yamamoto Takuya , Kutsuzawa Takaaki
Published: November 2022

In our previous study, a novel method combining underwater high-voltage plasma discharge with acoustic cavitation (ACAP) was developed and implemented using rhodamine B (RhB) as a model organic pollutant. Results revealed that injecting argon gas into the ACAP reactor positively influences RhB decomposition efficiency, but there is still further potential for improvement. The aim of this study was therefore to further improve the efficiency of the ACAP process through Fenton reactions. Two options for ferrous ion supply were considered: the addition of FeCl2 or the dissolution of iron from ACAP reactor steel parts into the RhB-containing solution. The results revealed that the degradation efficiency is increased by 20% due to the Fenton reactions when the concentration of ferrous ions reaches an optimal value. Lower pH was found to be desirable for the effect of Fenton reactions. Based on measurements using high performance liquid chromatography, a plausible mechanism of RhB degradation by the ACAP process assisted by Fenton reactions is additionally proposed and discussed.
Melatonin Attenuates Ischemic-like Cell Injury by Promoting Autophagosome Maturation via the Sirt1/FoxO1/Rab7 Axis in Hippocampal HT22 Cells and in Organotypic Cultures
Authors: Luchetti Francesca , Nasoni Maria G. , Burattini Sabrina , Mohammadi Atefeh , Pagliarini Marica , Canonico Barbara , Ambrogini Patrizia , Balduini Walter , Reiter Russel J. , Carloni Silvia
Published: November 2022

Dysfunctional autophagy is linked to neuronal damage in ischemia/reperfusion injury. The Ras-related protein 7 (Rab7), a member of the Rab family of small GTPases, appears crucial for the progression of the autophagic flux, and its activity is strictly interconnected with the histone deacetylase Silent information regulator 1 (Sirt1) and transcription factor Forkhead box class O1 (FoxO1). The present study assessed the neuroprotective role of melatonin in the modulation of the Sirt1/FoxO1/Rab7 axis in HT22 cells and organotypic hippocampal cultures exposed to oxygen-glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin re-established physiological levels of autophagy and reduced propidium iodide-positive cells, speeding up autophagosome (AP) maturation and increasing lysosomal activity. Our study revealed that melatonin modulates autophagic pathways, increasing the expression of both Rab7 and FoxO1 and restoring the Sirt1 expression affected by OGD/R. In addition, the Sirt1 inhibitor EX-527 significantly reduced Rab7, Sirt1, and FoxO1 expression, as well as autolysosomes formation, and blocked the neuroprotective effect of melatonin. Overall, our findings provide, for the first time, new insights into the neuroprotective role of melatonin against ischemic injury through the activation of the Sirt1/FoxO1/Rab7 axis.
The Role of NO/sGC/cGMP/PKG Signaling Pathway in Regulation of Platelet Function
Authors: Gambaryan Stepan
Published: November 2022

Circulating blood platelets are controlled by stimulatory and inhibitory factors, and a tightly regulated equilibrium between these two opposing processes is essential for normal platelet and vascular function. NO/cGMP/ Protein Kinase G (PKG) pathways play a highly significant role in platelet inhibition, which is supported by a large body of studies and data. This review focused on inconsistent and controversial data of NO/sGC/cGMP/PKG signaling in platelets including sources of NO that activate sGC in platelets, the role of sGC/PKG in platelet inhibition/activation, and the complexity of the regulation of platelet inhibitory mechanisms by cGMP/PKG pathways. In conclusion, we suggest that the recently developed quantitative phosphoproteomic method will be a powerful tool for the analysis of PKG-mediated effects. Analysis of phosphoproteins in PKG-activated platelets will reveal many new PKG substrates. A future detailed analysis of these substrates and their involvement in different platelet inhibitory pathways could be a basis for the development of new antiplatelet drugs that may target only specific aspects of platelet functions.
Redox Balance Differentially Affects Biomechanics in Permeabilized Single Muscle Fibres—Active and Passive Force Assessments with the Myorobot
Authors: Michael Mena , Kovbasyuk Larisa , Ritter Paul , Reid Michael B. , Friedrich Oliver , Haug Michael
Published: November 2022

An oxidizing redox state imposes unique effects on the contractile properties of muscle. Permeabilized fibres show reduced active force generation in the presence of H2O2. However, our knowledge about the muscle fibre’s elasticity or flexibility is limited due to shortcomings in assessing the passive stress–strain properties, mostly due to technically limited experimental setups. The MyoRobot is an automated biomechatronics platform that is well-capable of not only investigating calcium responsiveness of active contraction but also features precise stretch actuation to examine the passive stress–strain behaviour. Both were carried out in a consecutive recording sequence on the same fibre for 10 single fibres in total. We denote a significantly diminished maximum calcium-saturated force for fibres exposed to ≥500 µM H2O2, with no marked alteration of the pCa50 value. In contrast to active contraction (e.g., maximum isometric force activation), passive restoration stress (force per area) significantly increases for fibres exposed to an oxidizing environment, as they showed a non-linear stress–strain relationship. Our data support the idea that a highly oxidizing environment promotes non-linear fibre stiffening and confirms that our MyoRobot platform is a suitable tool for investigating redox-related changes in muscle biomechanics.
Electrochemical Sensing for Vitamins
Authors: Yang Yanting , Hu Ning , Deng Jinan , Yang Jun
Published: November 2022

Vitamins are essential and necessary nutrients for the human body. Rapid and accurate quantification of their levels in various samples has attracted much attention. Compared with traditional analytical methods, electrochemical techniques, with the advantages of low cost, high sensitivity, flexible detection strategies, easy integration, and miniaturization, have gradually become the main tools in vitamin detection. In this paper, the advance of electrochemical sensing of vitamins in recent years is reviewed. Firstly, the basics of different vitamins are briefly introduced. Then, the commonly-used electrodes and electrochemical methods for vitamin electrochemical detection, as well as the specific implementation strategy and performance, are described in detail. The development of miniaturization devices, especially microfluidic and microsensor devices, is also presented. Finally, the challenges faced by the electrochemical detection of vitamins are discussed, and future development is prospected.
Designing Culturally Responsive Education Strategies to Cultivate Young Children’s Cultural Identities: A Case Study of the Development of a Preschool Local Culture Curriculum
Authors: Shih Yi-Huang
Published: November 2022

The researcher investigated how the teachers at the preschool integrated the vision of the preschool, educational goals, and community resources to develop and implement the local culture curriculum as well as what problems they encountered in the process. Thereafter, the researcher developed strategies that can be used to solve such problems. The researcher discovered that the most important aspects of the local culture curriculum were (1) its ability to pique the children’s interest in history and the humanities through the lens of the children’s experiences at the market, and (2) its integration of local culture and the community, specifically through interactions between young children and adults at a vegetable market. The implementation of the local culture curriculum involved the following steps: (1) establishing a thematic network; (2) planning the activities, including exploring the children’s previous experiences and adjusting the curriculum and teaching methods accordingly; (3) conducting the activities, including visiting and participating in work at the market; (4) evaluating the activities; and (5) creating thank you cards and formulating plans for store renovation. Some of the obstacles the teachers encountered in the development and implementation of the vegetable-market-themed local culture curriculum were (1) shortages of preschool teachers willing to teach outdoor courses, (2) concerns about young children’s safety, and (3) young children’s lack of experience. Finally, on the basis of my conclusion, the researcher developed the following culturally responsive education strategies: (1) integrating aspects of local culture and the community into courses, (2) situating local culture courses in learning areas, (3) developing local culture curriculum that are rich in humanities, and (4) developing local culture curriculum based on parent–teacher cooperation to overcome teacher shortages at preschools. The results of this study may serve as a reference in the development of a local culture curriculum and other strategies to cultivate young children’s cultural identities.
The Impact of Different Pedagogical Models on Moderate-to-Vigorous Physical Activity in Physical Education Classes
Authors: Gouveia Élvio Rúbio , Lizandra Jorge , Martinho Diogo V. , França Cíntia , Ihle Andreas , Sarmento Hugo , Antunes Hélio , Correia Ana Luísa , Lopes Helder , Marques Adilson
Published: November 2022

The aims of this study were twofold: (i) to examine differences in physical activity (PA) variables regarding the length of Physical Education (PE) lessons (45 vs. 90 min) and teaching methodology (Teaching Games for Understanding (TGfU) or hybrid TGfU-sports education (SE)); and (ii) to estimate the percentage of time spent in moderate-to-vigorous (MV) PA assessed via an accelerometer based on total step count, BMI, age, and sex, considering the pedagogical models and the class length. This study was carried out in three classes of invasion games in PE. Two classes were taught based on TGfU (44 students, 18 males, 12.6 ± 0.55), and one was taught based on a hybrid TGfU-SE (17 students, 9 males, 13.7 ± 0.90). The same students were assessed twice, first in a 45 min class and then in a 90 min class. The students’ MVPA was assessed using the Actigraph GT3X Activity Monitor. The results revealed significant differences in PA intensity regarding the length of the PE lesson (45 vs. 90 min) and the teaching methodology. The 45 min classes using TGfU were more intense and had less sedentary time than the 90 min classes. When using a hybrid TGfU-SE, the 90 min classes had higher intensities than the 45 min classes. Generally, when comparing the two types of pedagogical intervention, the TGfU model provided more active lessons and less sedentary time in class than a hybrid TGfU-SE. The TGfU model is more profitable for increasing MVPA in class. Due to the issues related to the organization and management of sports practice in class, several recommendations for maximizing MVPA in a hybrid TGfU-SE class must be considered.