bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot-Spot-Specific Probe (HSSP) for Rapid and Accurate Detection of KRAS Mutations in Colorectal Cancer
Authors: Lee Hyo Joo , Koo Bonhan , Jang Yoon Ok , Liu Huifang , Dao Thuy Nguyen Thi , Lim Seok-Byung , Shin Yong
Published: August 2022

Detection of oncogene mutations has significance for early diagnosis, customized treatment, treatment progression, and drug resistance monitoring. Here, we introduce a rapid, sensitive, and specific mutation detection assay based on the hot-spot-specific probe (HSSP), with improved clinical utility compared to conventional technologies. We designed HSSP to recognize KRAS mutations in the DNA of colorectal cancer tissues (HSSP-G12D (GGT→GAT) and HSSP-G13D (GGC→GAC)) by integration with real-time PCR. During the PCR analysis, HSSP attaches to the target mutation sequence for interference with the amplification. Then, we determine the mutation detection efficiency by calculating the difference in the cycle threshold (Ct) values between HSSP-G12D and HSSP-G13D. The limit of detection to detect KRAS mutations (G12D and G13D) was 5–10% of the mutant allele in wild-type populations. This is superior to the conventional methods (≥30% mutant allele). In addition, this technology takes a short time (less than 1.5 h), and the cost of one sample is as low as USD 2. We verified clinical utility using 69 tissue samples from colorectal cancer patients. The clinical sensitivity and specificity of the HSSP assay were higher (84% for G12D and 92% for G13D) compared to the direct sequencing assay (80%). Therefore, HSSP, in combination with real-time PCR, provides a rapid, highly sensitive, specific, and low-cost assay for detecting cancer-related mutations. Compared to the gold standard methods such as NGS, this technique shows the possibility of the field application of rapid mutation detection and may be useful in a variety of applications, such as customized treatment and cancer monitoring.
Detection of S2− in Water by a Glucose Enhanced Water-Soluble Fluorescent Bioprobe
Authors: An Xingwang , Wang Yi , Li Jiahui , Pei Zhichao , Pei Yuxin
Published: August 2022

That sulfide anions (S2−) in aquatic environments are produced by microorganisms through degrading sulfur-containing proteins and other organics are harmful to human health. Thus, it is of significance to develop a convenient method for the detection of S2− in water. Small molecular fluorescent probes are very popular for their advantages of visualization, real-time, high sensitivity, and convenience. However, low solubility in water limits the application of existing S2− probes. In this work, we found that our previously developed water-soluble glycosylated fluorescent bioprobe Cu[GluC] can achieve detection of S2− in water. Cu[GluC] can restore fluorescence within 20 s when it encounters S2− and shows good sensitivity towards S2− with a detection limit of 49.6 nM. Besides, Cu[GluC] derived fluorescent test strips were obtained by immersion and realized conveniently visual S2− detection in water by coupling with a UV lamp and a smartphone app. This work provides a fluorescent bioprobe with good water solubility as well as its derived fluorescent test strip for sensitive and simple detection of S2− in water, which shows good prospects in on-site water quality monitoring.
Distribution and Morphological Characteristics of Oligodendrocytes in Selected Areas of the Brain of Male and Female Red Kangaroos (Macropus rufus)
Authors: Wawrzyniak Agata , Balawender Krzysztof , Lalak Roman , Golan Maciej Przemysław , Wróbel Konrad , Boroń Dariusz , Staszkiewicz Rafał , Grabarek Beniamin Oskar
Published: August 2022

This study was carried out on six adult red kangaroos of both sexes. To determine the location of the oligodendrocytes (OLGs) of the hippocampus (Hip) and corpus callosum (CC), the method of impregnation of the neuroglia with silver salts was applied. The iron distribution in the OLGs was determined by the histochemical method. The Nissl method was used to determine the location of the brain structure and to analyze the number of OLGs. In the Hip, these cells are located one beside another, mainly in blood vessels and neurons; in the neocortex (NC), they are located in layers I–VI; and in the CC, they are arranged in characteristic rows and accompany both nerve fibers and blood vessels. The analysis of the results obtained by the chosen methods in the Hip, NC, and CC in males and females did not show statistically significant differences in the distribution and location of the red kangaroo OLGs. The involvement of these cells is a physiological process that proceeds in a similar manner throughout the life of individuals and actively influences the metabolism of neurons and myelin.
Measurement of Extraneous and Germane Cognitive Load in the Mathematics Addition Task: An Event-Related Potential Study
Authors: Wang Chao-Chih , Cheng Peter Kuan-Hao , Wang Tzu-Hua
Published: August 2022

Cognitive load significantly influences learning effectiveness. All the three types of cognitive load—intrinsic, extraneous, and germane—are important for guiding teachers in preparing effective instructional designs for students. However, the techniques used to assess the relationship between brain activity and cognitive load during learning activities require further investigation. This study preliminarily examined cognitive load during mathematics computations based on cognitive-load theory. We used event-related potentials to compare carryover and without carryover additions under three types of stimuli (uncoloured Arabic numerals, colourful Arabic numerals, and Chinese numerals) to measure learners’ cognitive load. According to the concept and rationale of cognitive-load theory, the design defined the extraneous and germane cognitive load to measure the N1 and P2 components and the relevant behavioural data. The highest P2 amplitude was observed in the Chinese numerals condition as extraneous cognitive load, and the N1 component was observed in the colourful Arabic numerals condition as germane cognitive load. Thus, both components may play an important role in extraneous and germane cognitive load. Additionally, these exhibit negative correlations during mathematical computations. This study’s findings and implications offer insights into future ways for assessing cognitive load using brain imaging techniques and potential applications for brain–computer interfaces.
Nerve Conduction Studies of Dorsal Sural Nerve: Normative Data and Its Potential Application in ATTRv Pre-Symptomatic Subjects
Authors: Luigetti Marco , Guglielmino Valeria , Romozzi Marina , Romano Angela , Di Paolantonio Andrea , Bisogni Giulia , Sabatelli Eleonora , Modoni Anna , Sabatelli Mario , Servidei Serenella , Lo Monaco Mauro
Published: August 2022

The objective of the study is to provide age-related normative values for dorsal sural nerve (DSN) and to analyse its application during follow-up of hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic subjects. We consecutively recruited ATTRv pre-symptomatic carriers in which clinical examination, cardiological evaluation, and nerve conduction studies of the sural nerve and DSN were performed. To provide normative data of DSN, neurophysiologic parameters from healthy controls referred to our service were entered into linear regression analyses to check the relative influence of age and height. A correction grid was then derived. We collected 231 healthy subjects: the mean DSN sensory nerve action potential (SNAP) amplitude was 9.99 ± 5.48 μV; the mean conduction velocity was 49.01 ± 5.31 m/s. Significant correlations were found between age and height with DSN SNAP amplitude. Fifteen ATTRv pre-symptomatic carriers were examined. Sural nerve NCS were normal in 12/15 and revealed low/borderline values in three subjects. Considering our correction grid, we found an abnormal DNS amplitude in 9/15 subjects and low/borderline values in 2/15. In ATTRv, early detection of peripheral nerve damage is crucial to start a disease-modifying treatment. DSN may be easily and reliably included in the routine neurophysiological follow-up of ATTRv pre-symptomatic subjects.
The Influence of Neurotrophic Factors BDNF and GDNF Overexpression on the Functional State of Mice and Their Adaptation to Audiogenic Seizures
Authors: Kustova Angelina O. , Gavrish Maria S. , Sergeeva Marina A. , Avlasenko Daria A. , Kiseleva Anna O. , Epifanova Ekaterina A. , Babaev Alexey A. , Mishchenko Tatiana A. , Vedunova Maria V.
Published: August 2022

The high prevalence of diagnosed cases of severe neurological disorders, a significant proportion of which are epilepsy, contributes to a high level of mortality and disability in the population. Neurotrophic factors BDNF and GNDF are considered promising agents aimed at increasing the central nervous system’s adaptive potential for the development of the epileptiform activity. Despite the pronounced neuroprotective and anticonvulsant potential, an appropriate way to stimulate these endogenous signaling molecules with minimal risk of side effects remains an open question. Herein, we assessed the safety of gene therapy using original adeno-associated viral constructs carrying the genes of neurotrophic factors BDNF and GDNF in the early postnatal period of development of experimental animals. The intraventricular injection of AAV-Syn-BDNF-eGFP and AAV-Syn-GDNF-eGFP viral constructs into newborn mice was found to provide persistent overexpression of target genes in the hippocampus and cerebral cortex in vivo for four weeks after injection. The application of viral constructs has a multidirectional effect on the weight and body length characteristics of mice in the early postnatal period; however, it ensures the animals’ resistance to the development of seizure activity under audiogenic stimulation in the late postnatal period and preserves basic behavioral reactions, emotional status, as well as the mnestic and cognitive abilities of mice after simulated stress. Our results demonstrated the safety of using the AAV-Syn-BDNF-eGFP and AAV-Syn-GDNF-eGFP viral constructs in vivo, which indicates the expediency of further testing the constructs as therapeutic anticonvulsants.
Machine Learning-Based Model for Predicting the Shear Strength of Slender Reinforced Concrete Beams without Stirrups
Authors: Alshboul Odey , Almasabha Ghassan , Shehadeh Ali , Mamlook Rabia Emhamed Al , Almuflih Ali Saeed , Almakayeel Naif
Published: August 2022

The influence of concrete mix properties on the shear strength of slender structured concrete beams without stirrups (SRCB-WS) is a widespread point of contention. Over the past six decades, the shear strength of SRCB-WS has been studied extensively in both experimental and theoretical contexts. The most recent version of the ACI 318-19 building code requirements updated the shear strength equation for SRCB-WS by factoring in the macroeconomic factors and the contribution of the longitudinal steel structural ratio. However, the updated equation still does not consider the effect of the shear span ratio (a/d) and the yield stress of longitudinal steel rebars (Fy). Therefore, this study investigates the importance of the most significant potential variables on the shear strength of SRCB-WS to help develop a gene expression-based model to estimate the shear strength of SRCB-WS. A database of 784 specimens was used from the literature for training and testing the proposed gene expression algorithm for forecasting the shear strength of SRCB-WS. The collected datasets are comprehensive, wherein all considered concrete properties were considered over the previous 68 years. The performance of the suggested algorithm versus the ACI 318-19 equation was statistically evaluated using various measures, such as root mean square error, mean absolute error, mean absolute percentage error, and the coefficient of determination. The evaluation results revealed the superior performance of the proposed model over the current ACI 318-19 equation. In addition, the proposed model is more comprehensive and considers additional variables, including the effect of the shear span ratio and the yield stress of longitudinal steel rebars. The developed model reflects the power of employing gene expression algorithms to design reinforced concrete elements with high accuracy.
Correction: Brüning-Richardson et al. GSK-3 Inhibition Is Cytotoxic in Glioma Stem Cells through Centrosome Destabilization and Enhances the Effect of Radiotherapy in Orthotopic Models. Cancers 2021, 13, 5939
Authors: Brüning-Richardson Anke , Shaw Gary C. , Tams Daniel , Brend Tim , Sanganee Hitesh , Barry Simon T. , Hamm Gregory , Goodwin Richard J. A. , Swales John G. , King Henry , Steele Lynette , Morton Ruth , Widyadari Anastasia , Ward Thomas A. , Esteves Filomena , Boissinot Marjorie , Mavria Georgia , Droop Alastair , Lawler Sean E. , Short Susan C.
Published: August 2022

The authors wish to make the following corrections to this paper [1] [...]
Revealing the Increased Stress Response Behavior through Transcriptomic Analysis of Adult Zebrafish Brain after Chronic Low to Moderate Dose Rates of Ionizing Radiation
Authors: Cantabella Elsa , Camilleri Virginie , Cavalie Isabelle , Dubourg Nicolas , Gagnaire Béatrice , Charlier Thierry D. , Adam-Guillermin Christelle , Cousin Xavier , Armant Oliver
Published: August 2022

High levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior.
Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma—A Lingering Pitfall of the Long Latency
Authors: Chen Yung-Hsuan , Luo Sheng-Dean , Wu Shao-Chun , Wu Ching-Nung , Chiu Tai-Jan , Wang Yu-Ming , Yang Yao-Hsu , Chen Wei-Chih
Published: August 2022

Purpose: To investigate the clinical characteristics, risk factors, and clinical outcomes of long-latent recurrence (>five years) of nasopharyngeal carcinoma (NPC). Methods: This retrospective study enrolled newly diagnosed NPC patients from the Chang Gung Research Database between January 2007 and December 2019. We analyzed the patients’ characteristics and survival outcomes after recurrence. Results: A total of 2599 NPC patients were enrolled. The overall recurrence rate was 20.5%, while 8.1% of patients had long-latent recurrence (>five years). These patients had a higher percentage of initial AJCC (The American Joint Committee on Cancer) stage I/II (60.5%, p = 0.001) and local recurrence (46.5%, p < 0.001). Unresectable rT3 and rT4 were found in 60% of patients when recurrence and 30% of local recurrence occurred in the skull base, which could not be detected by the regular endoscopy. The five-year overall survival rate of long-latent recurrence was 19.7%. Alive patients tended to be asymptomatic but have regular follow-ups with the interval less than six months. Multivariate analysis showed age and initial advanced AJCC stages were independent risk factors of death after recurrence. In contrast, patients with recurrence between two and five years, salvage surgeries, and regional recurrence had favorable survival outcomes. Conclusion: Long-latent NPC recurrence is not rare, and the survival outcome is poor. Regular follow-up for early detection of NPC recurrence is necessary even after five years of disease-free period.
Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer
Authors: Diamant Elliott , Roumiguié Mathieu , Ingels Alexandre , Parra Jérôme , Vordos Dimitri , Bajeot Anne-Sophie , Chartier-Kastler Emmanuel , Soulié Michel , de la Taille Alexandre , Rouprêt Morgan , Seisen Thomas
Published: August 2022

Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG. Perioperative outcomes were evaluated and the impact of upfront vs. delayed eRC on pathological upstaging, defined as ≥pT2N0 disease at final pathology, was assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS) were compared between upfront and delayed eRC groups using inverse probability of treatment weighting (IPTW)-adjusted Cox model. Results: Overall, 184 patients received either upfront (n = 87; 47%) or delayed (n = 97; 53%) eRC. No difference was observed in perioperative outcomes between the two treatment groups (all p > 0.05). Pathological upstaging occurred in 55 (30%) patients and upfront eRC was an independent predictor (HR = 2.65; 95% CI = (1.23–5.67); p = 0.012). In the IPTW-adjusted Cox analysis, there was no significant difference between upfront and delayed eRC in terms of RFS (HR = 1.31; 95% CI = (0.72–2.39); p = 0.38), CSS (HR = 1.09; 95% CI = (0.51–2.34); p = 0.82) and OS (HR = 1.19; 95% CI = (0.62–2.78); p = 0.60). Conclusion: our results suggest similar perioperative outcomes between upfront and delayed eRC, with an increased risk of upstaging after upfront eRC that did impact survival, as compared to delayed eRC.
Radiomics-Based Deep Learning Prediction of Overall Survival in Non-Small-Cell Lung Cancer Using Contrast-Enhanced Computed Tomography
Authors: Hou Kuei-Yuan , Chen Jyun-Ru , Wang Yung-Chen , Chiu Ming-Huang , Lin Sen-Ping , Mo Yuan-Heng , Peng Shih-Chieh , Lu Chia-Feng
Published: August 2022

Patient outcomes of non-small-cell lung cancer (NSCLC) vary because of tumor heterogeneity and treatment strategies. This study aimed to construct a deep learning model combining both radiomic and clinical features to predict the overall survival of patients with NSCLC. To improve the reliability of the proposed model, radiomic analysis complying with the Image Biomarker Standardization Initiative and the compensation approach to integrate multicenter datasets were performed on contrast-enhanced computed tomography (CECT) images. Pretreatment CECT images and the clinical data of 492 patients with NSCLC from two hospitals were collected. The deep neural network architecture, DeepSurv, with the input of radiomic and clinical features was employed. The performance of survival prediction model was assessed using the C-index and area under the curve (AUC) 8, 12, and 24 months after diagnosis. The performance of survival prediction that combined eight radiomic features and five clinical features outperformed that solely based on radiomic or clinical features. The C-index values of the combined model achieved 0.74, 0.75, and 0.75, respectively, and AUC values of 0.76, 0.74, and 0.73, respectively, 8, 12, and 24 months after diagnosis. In conclusion, combining the traits of pretreatment CECT images, lesion characteristics, and treatment strategies could effectively predict the survival of patients with NSCLC using a deep learning model.
Metabolic Pathways as a Novel Landscape in Pancreatic Ductal Adenocarcinoma
Authors: Ali Ahmad , Chianese Ugo , Papulino Chiara , Toraldo Antonella , Abakar Mawada Elmagboul Abdalla , Passaro Eugenia , Cennamo Rosario , Del Gaudio Nunzio , Altucci Lucia , Benedetti Rosaria
Published: August 2022

Metabolism plays a fundamental role in both human physiology and pathology, including pancreatic ductal adenocarcinoma (PDAC) and other tumors. Anabolic and catabolic processes do not only have energetic implications but are tightly associated with other cellular activities, such as DNA duplication, redox reactions, and cell homeostasis. PDAC displays a marked metabolic phenotype and the observed reduction in tumor growth induced by calorie restriction with in vivo models supports the crucial role of metabolism in this cancer type. The aggressiveness of PDAC might, therefore, be reduced by interventions on bioenergetic circuits. In this review, we describe the main metabolic mechanisms involved in PDAC growth and the biological features that may favor its onset and progression within an immunometabolic context. We also discuss the need to bridge the gap between basic research and clinical practice in order to offer alternative therapeutic approaches for PDAC patients in the more immediate future.
Strategies for Radioiodine Treatment: What’s New
Authors: Sparano Clotilde , Moog Sophie , Hadoux Julien , Dupuy Corinne , Al Ghuzlan Abir , Breuskin Ingrid , Guerlain Joanne , Hartl Dana , Baudin Eric , Lamartina Livia
Published: August 2022

Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.
A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis
Authors: Enikeev Dmitry , Morozov Andrey , Babaevskaya Diana , Bazarkin Andrey , Malavaud Bernard
Published: August 2022

The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR “circulating tumor cells” OR “liquid biopsy”) AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers.
Artificial Intelligence in Colorectal Cancer Surgery: Present and Future Perspectives
Authors: Quero Giuseppe , Mascagni Pietro , Kolbinger Fiona R. , Fiorillo Claudio , De Sio Davide , Longo Fabio , Schena Carlo Alberto , Laterza Vito , Rosa Fausto , Menghi Roberta , Papa Valerio , Tondolo Vincenzo , Cina Caterina , Distler Marius , Weitz Juergen , Speidel Stefanie , Padoy Nicolas , Alfieri Sergio
Published: August 2022

Artificial intelligence (AI) and computer vision (CV) are beginning to impact medicine. While evidence on the clinical value of AI-based solutions for the screening and staging of colorectal cancer (CRC) is mounting, CV and AI applications to enhance the surgical treatment of CRC are still in their early stage. This manuscript introduces key AI concepts to a surgical audience, illustrates fundamental steps to develop CV for surgical applications, and provides a comprehensive overview on the state-of-the-art of AI applications for the treatment of CRC. Notably, studies show that AI can be trained to automatically recognize surgical phases and actions with high accuracy even in complex colorectal procedures such as transanal total mesorectal excision (TaTME). In addition, AI models were trained to interpret fluorescent signals and recognize correct dissection planes during total mesorectal excision (TME), suggesting CV as a potentially valuable tool for intraoperative decision-making and guidance. Finally, AI could have a role in surgical training, providing automatic surgical skills assessment in the operating room. While promising, these proofs of concept require further development, validation in multi-institutional data, and clinical studies to confirm AI as a valuable tool to enhance CRC treatment.
NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells
Authors: Panieri Emiliano , Pinho Sónia A. , Afonso Gonçalo J. M. , Oliveira Paulo J. , Cunha-Oliveira Teresa , Saso Luciano
Published: August 2022

The NRF2–KEAP1 system is a fundamental component of the cellular response that controls a great variety of transcriptional targets that are mainly involved in the regulation of redox homeostasis and multiple cytoprotective mechanisms that confer adaptation to the stress conditions. The pleiotropic response orchestrated by NRF2 is particularly relevant in the context of oncogenic activation, wherein this transcription factor acts as a key driver of tumor progression and cancer cells’ resistance to treatment. For this reason, NRF2 has emerged as a promising therapeutic target in cancer cells, stimulating extensive research aimed at the identification of natural, as well as chemical, NRF2 inhibitors. Excitingly, the influence of NRF2 on cancer cells’ biology extends far beyond its mere antioxidant function and rather encompasses a functional crosstalk with the mitochondrial network that can influence crucial aspects of mitochondrial homeostasis, including biogenesis, oxidative phosphorylation, metabolic reprogramming, and mitophagy. In the present review, we summarize the current knowledge of the reciprocal interrelation between NRF2 and mitochondria, with a focus on malignant tumors and cancer stem cells.
Special Issue on “Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis II”
Authors: Weiskirchen Ralf
Published: August 2022

Hepatic fibrosis is a common type of liver disease that is attracting increasing attention of basic scientists and clinicians worldwide [...]
Cocaine Self-Administration Influences Central Nervous System Immune Responses in Male HIV-1 Transgenic Rats
Authors: Ezeomah Chiomah , Fongsaran Chanida , Persons Amanda L. , Napier T. Celeste , Cisneros Irma E.
Published: August 2022

Cocaine use increases the neurotoxic severity of human immunodeficiency virus-1 (HIV-1) infection and the development of HIV-associated neurocognitive disorders (HAND). Among the studied cellular mechanisms promoting neurotoxicity in HIV-1 and cocaine use, central nervous system (CNS) immunity, such as neuroimmune signaling and reduced antiviral activity, are risk determinants; however, concrete evidence remains elusive. In the present study, we tested the hypothesis that cocaine self-administration by transgenic HIV-1 (HIV-1Tg) rats promotes CNS inflammation. To test this hypothesis, we measured cytokine, chemokine, and growth factor protein levels in the frontal cortex (fCTX) and caudal striatum (cSTR). Our results demonstrated that cocaine self-administration significantly increased fCTX inflammation in HIV-1Tg rats, but not in the cSTR. Accordingly, we postulate that cocaine synergizes with HIV-1 proteins to increase neuroinflammation in a region-selective manner, including the fCTX. Given the fCTX role in cognition, this interaction may contribute to the hyperimmunity and reduced antiviral activity associated with cocaine-mediated enhancement of HAND.
Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
Authors: Matei Nathanael , Leahy Sophie , Blair Norman P. , Burford James , Rahimi Mansour , Shahidi Mahnaz
Published: August 2022

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aβ) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal vascular biomarkers may improve knowledge of AD pathophysiology and potentially serve as therapeutic targets. The purpose of the current study was to test the hypothesis that retinal hemodynamic and oxygen metrics are altered in 5XFAD mice. Methods: Thirty-two male mice were evaluated at 3 months of age: sixteen 5XFAD transgenic and sixteen wild-type mice. Spectral-domain optical coherence tomography, vascular oxygen tension, and blood flow imaging were performed in one eye of each mouse. After imaging, the imaged and fellow retinal tissues were submitted for histological sectioning and amyloid protein analysis, respectively. Protein analysis was also performed on the brain tissues. Results: Retinal physiological changes in venous diameter and blood velocity, arterial and venous oxygen contents, coupled with anatomical alterations in the thickness of retinal cell layers were detected in 5XFAD mice. Moreover, an increase in Aβ42 levels in both the retina and brain tissues was observed in 5XFAD mice. Significant changes in retinal oxygen delivery, metabolism, or extraction fraction were not detected. Based on compiled data from both groups, arterial oxygen content was inversely related to venous blood velocity and nerve fiber/ganglion cell layer thickness. Conclusions: Concurrent alterations in retinal hemodynamic and oxygen metrics, thickness, and tissue Aβ42 protein levels in 5XFAD mice at 3 months of age corresponded to previously reported findings in human AD. Overall, these results suggest that this mouse model can be utilized for studying pathophysiology of AD and evaluating potential therapies.
NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease
Authors: Curtis William M. , Seeds William A. , Mattson Mark P. , Bradshaw Patrick C.
Published: August 2022

Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection of mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. The downstream effects include oxidative damage, failure to maintain proteostasis and ion gradients, and decreased NAD+ and NADPH levels, resulting in insufficient energy metabolism and neurotransmitter synthesis. A ketosis-based metabolic therapy that increases the levels of (R)-3-hydroxybutyrate (BHB) may reverse the dysfunctional MQC by partially replacing glucose as an energy source, by stimulating mitophagy, and by decreasing inflammation. Fasting can potentially raise cytoplasmic NADPH levels by increasing the mitochondrial export and cytoplasmic metabolism of ketone body-derived citrate that increases flux through isocitrate dehydrogenase 1 (IDH1). NADPH is an essential cofactor for nitric oxide synthase, and the nitric oxide synthesized can diffuse into the mitochondrial matrix and react with electron transport chain-synthesized superoxide to form peroxynitrite. Excessive superoxide and peroxynitrite production can cause the opening of the mitochondrial permeability transition pore (mPTP) to depolarize the mitochondria and activate PINK1-dependent mitophagy. Both fasting and exercise increase ketogenesis and increase the cellular NAD+/NADH ratio, both of which are beneficial for neuronal metabolism. In addition, both fasting and exercise engage the adaptive cellular stress response signaling pathways that protect neurons against the oxidative and proteotoxic stress implicated in PD. Here, we discuss how intermittent fasting from the evening meal through to the next-day lunch together with morning exercise, when circadian NAD+/NADH is most oxidized, circadian NADP+/NADPH is most reduced, and circadian mitophagy gene expression is high, may slow the progression of PD.
Effect of Artificial Freeze/Thaw and Thermal Shock Ageing, Combined or Not with Salt Crystallisation on the Colour of Zamora Building Stones (Spain)
Authors: García-Talegón Jacinta , Iñigo Adolfo Carlos , Sepúlveda Rosa , Azofra Eduardo
Published: August 2022

After subjecting Zamora building stones to accelerated ageing tests, colour changes were studied, namely: (a) freezing/thawing and thermal shock (gelifraction and thermoclasty), and (b) combination of freezing/thawing plus thermal shock and salt crystallisation (sulphates or phosphates) (gelifraction, thermoclasty and haloclasty). Zamora building stones are silicified conglomerates (silcretes) from the Cretaceous that show marked colour changes due to the remobilisation of iron oxyhydroxides. In this work, four varieties were: white stone; ochreous stone; white and red stone; and purple stone Their micromorphological characterization (skeleton, weathering plasma and porosity/cutan) is formed of grains and fragments of quartz and quartzite as well as by accesory minerals muscovite and feldspar (more or less altered), and some opaque. Quartz, feldspar and illite/mica were part of the skeleton; kaolinite, iron oxyhydroxides, and CT opal were part of the weathering plasma or cutans; their porosity were 11.7–8.7%. Their chromatic data have been statistically analysed (MANOVA-Biplot). They showed higher variations in ΔE*, ΔL*, Δa* and Δb*on combined freezing/thawing plus thermal shock and sulphates crystallisation leading to rapid alteration of the building stones. Chromatic differences between the other two artificial ageing tests were less evident and were not detected in all samples. The global effect of ageing on the Zamora building stones darkened them and reduced their yellowing. The ochreous stone suffered the least variation and the purple stone the most. This study of the colour by statistical analyse may be of interest for the evaluation and monitoring of stone decay, which is an inexpensive, simple, easy and non-destructive technique.
Chiral Recognition with Broad Selective Sensor Arrays
Authors: Magna Gabriele , Stefanelli Manuela , Pomarico Giuseppe , Naitana Mario Luigi , Monti Donato , Di Natale Corrado , Paolesse Roberto
Published: August 2022

The detection and discrimination of chiral analytes has always been a topical theme in food and pharmaceutical industries and environmental monitoring, especially when dealing with chiral drugs and pesticides, whose enantiomeric nature assessment is of crucial importance. The typical approach matches novel chiral receptors designed ad hoc for the discrimination of a target enantiomer with emerging nanotechnologies. The massive synthetic efforts requested and the difficulty of analyzing complex matrices warrant the ever-growing exploitation of sensor array as an alternative route, using a limited number of chiral or both chiral and achiral sensors for the stereoselective identification and dosing of chiral compounds. This review aims to illustrate a little-explored winning strategy in chiral sensing based on sensor arrays. This strategy mimics the functioning of natural olfactory systems that perceive some couples of enantiomeric compounds as distinctive odors (i.e., using an array of a considerable number of broad selective receptors). Thus, fundamental concepts related to the working principle of sensor arrays and the role of data analysis techniques and models have been briefly presented. After the discussion of existing examples in the literature using arrays for discriminating enantiomers and, in some cases, determining the enantiomeric excess, the remaining challenges and future directions are outlined for researchers interested in chiral sensing applications.
Functional Ferroic Materials, Films and Devices
Authors: Guan Pengfei , Zheng Ming
Published: August 2022

Ferroic materials (e [...]
Modification of Cold-Sprayed Cu-Al-Ni-Al2O3 Composite Coatings by Friction Stir Technique to Enhance Wear Resistance Performance
Authors: Dzhurinskiy Dmitry , Babu Abhishek , Dautov Stanislav , Lama Anil , Mangrulkar Mayuribala
Published: August 2022

An innovative hybrid process combining two effective surface modification techniques, cold spray (CS) and friction stir processing (FSP), was proposed to refine the microstructure of Cu-Al-Ni-Al2O3 composite coating material. FSP was performed under constant rpm using extensive cooling conditions to remove heat generated during the operation. Microstructural characterizations such as optical micrography (OM), scanning electron microscopy (SEM), Electron Backscatter Diffraction (EBSD), Energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) were performed to evaluate the microstructural evolution of the coatings before and after FSP treatment. Mechanical characterizations such as microhardness and elastic modulus were measured using micro-depth sensing techniques. Furthermore, sliding wear tests were performed to study the wear resistance of the as-sprayed and processed coatings. The findings suggest that after FSP, there is an improvement in microstructure of the coating layers with the elimination of particle boundaries, micro-pores and micro-cracks, and processed coatings showed an improvement in mechanical properties. Furthermore, there was a slight reduction in the wear rate of the deposited CuAlNi-Al2O3 composite coatings. Among all the test coatings, friction stir processed S1 coating showed the lowest wear rate, which was an almost two times lower wear rate than its unprocessed counterparts.
First-Principles Calculations to Investigate the Oxidation Mechanism of Pristine MoS2 and Ti-Doped MoS2
Authors: Leng Senlin , Zhang Qiao , Guo Lei , Huang Yue , Ebenso Eno E. , Marzouki Riadh
Published: August 2022

Generally, MoS2 is easily oxidized when exposed to oxygen, and the antioxidation mechanism of MoS2 is still a challenge. Thus, more efforts were made to greatly improve its antioxidation performance. It was reported that the Ti atom doped with MoS2 was treated as the effective method to enhance its antioxidation performance; however, the detailed antioxidation mechanism was not well understood. Superior to experimental methods, the first-principles method could provide deep insight into the atomic information and serve as a useful tool to gain an understanding of the antioxidation mechanisms of the doped MoS2; thus, the antioxidation behavior of the Ti-doped MoS2 was investigated in detail using first-principles calculations. However, an opposing conclusion was obtained from the calculated results compared to the previous experimental results; that is, the incorporation of the Ti atom was not helpful for improving the antioxidation performance of MoS2. The strange phenomenon was well probed and discussed in detail, and understanding the oxidation mechanism of the Ti-doped MoS2 would be helpful for expanding its applications in the ambient atmosphere.
Composite Films for Time Measurement—A Case Study
Authors: Carotenuto Gianfranco
Published: August 2022

Each event starts in the past and proceeds towards the future, going through the present [...]
Study Design on the Presence of Metals in Moisturisers, and Compliance with Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of the European Union, on Cosmetic Products
Authors: Rujido-Santos Iria , Herbello-Hermelo Paloma , Barciela-Alonso María Carmen , Bermejo-Barrera Pilar , Moreda-Piñeiro Antonio
Published: August 2022

Metals are present in cosmetics due to deliberate addition by the manufacturers, contamination of raw materials, and/or contamination during their manufacture or storage. The objective of this work was to explore the metal content in the most-consumed moisturising creams on the Spanish market, to verify their degree of compliance with Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of the European Union, regarding the presence of metals in cosmetics. The moisturisers were digested (microwave-assisted acid digestion) and analysed by inductively coupled plasma-mass spectrometry (ICP-MS), for metal assessment. The ICP-MS measurements were successfully validated (RSDs lower than 5% and analytical recoveries within the 91–110% range). Metals banned in cosmetics were found at very low concentrations in some of the moisturisers, as inevitable traces of pollutants. This was the case with beryllium (found in only two samples, at concentrations lower than 0.10 µg g−1), cadmium (found at 0.075 µg g−1 in one sample), mercury (found in four samples at concentrations within the 0.10–0.18 µg g−1 range), and lead (also found in four samples at concentrations from 0.03 to 0.44 µg g−1). Furthermore, nickel (0.16–0.56 µg g−1, six samples), chromium (0.09–0.30 µg g−1, three samples), and cobalt (lower than 0.13 µg g−1, two samples) were also found in the analysed creams.
Attribute-Based Encryption in Securing Big Data from Post-Quantum Perspective: A Survey
Authors: Jemihin Zulianie Binti , Tan Soo Fun , Chung Gwo-Chin
Published: August 2022

Attribute-based encryption (ABE) cryptography is widely known for its potential to solve the scalability issue of recent public key infrastructure (PKI). It provides a fine-grained access control system with high flexibility and efficiency by labeling the secret key and ciphertext with distinctive attributes. Due to its fine-grained features, the ABE scheme is a protection layer in securing users’ data and privacy in big data processing and analytics. However, quantum computing, new technology on the horizon that will transform the security and privacy environment, has begun to appear. Like the conventional ABE schemes, present cryptography is not excluded from the impacts of quantum technology as they are not made to be quantum-resistant. While most recent surveys generally touched on the generic features of attribute-based encryption schemes such as user revocation, scalability, flexibility, data confidentiality, and scope in pairing-based ABE schemes, this survey investigated quantum-resistant ABE schemes in securing big data. This survey reviews the challenges faced by the recent ABE cryptography in the post-quantum era and highlights its differences from the conventional pairing-based ABE schemes. Subsequently, we defined the criteria of an ideal quantum-resistant ABE scheme. Additionally, existing works on quantum-resistant ABE schemes are reviewed based on their algorithms design, security and functionalities. Lastly, we summarized quantum-resistant ABE schemes’ ongoing challenges and future works.
Electron Transport Layer-Free Ruddlesden–Popper Two-Dimensional Perovskite Solar Cells Enabled by Tuning the Work Function of Fluorine-Doped Tin Oxide Electrodes
Authors: Dong Ningfei , Zhou Haosu , Wang Lei , Liu Zhihai
Published: August 2022

Organic–inorganic halide two-dimensional (2D) layered perovskites have been demonstrated to have better environmental stability than conventional three-dimensional perovskites. In this study, we investigate the fabrication of electron transport layer (ETL)-free Ruddlesden–Popper 2D perovskite solar cells (PSCs) by tuning the work function of a fluorine-doped tin oxide (FTO) electrode. With the deposition of polyethylenimine (PEIE) onto its surface, the work function of the FTO electrode could be raised from −4.72 to −4.08 eV, which is more suitable for electron extraction from the perovskite absorber. Using this technique, the ETL-free 2D PSCs exhibited an excellent power conversion efficiency (PCE) of 12.7% (on average), which is substantially higher than that of PSCs fabricated on a pristine FTO electrode (9.6%). Compared with the PSCs using TiO2, the ETL-free PSCs could be fabricated under a low processing temperature of 100 °C with excellent long-term stability. After 15 days, the FTO/PEIE-based ETL-free PSCs showed a PCE degradation of 16%, which is significantly lower than that of the TiO2-based case (29%). The best-performing PSC using a FTO/PEIE cathode showed a high PCE of 13.0%, with a small hysteresis degree of 2.3%.
Prediction of Residual Stress Distribution in NM450TP Wear-Resistant Steel Welded Joints
Authors: Li Guannan , Feng Guangjie , Wang Chongyang , Hu Long , Li Tao , Deng Dean
Published: August 2022

This study developed a thermo-metallurgical-mechanical simulation method to calculate the temperature field and residual stress distribution in the NM450TP wear-resistant steel welded joints. During the simulation, the solid-state phase transformation and softening effect of NM450TP wear-resistant steel was considered. The simulation results were compared with the experimental results, which verified the feasibility of this method. The influences of solid-state phase transformation and softening effect on the welding residual stress distribution were discussed. The numerical simulation results showed that the solid-state phase transformation had a more significant effect on the magnitude and distribution of the longitudinal residual stress than that of the transverse residual stress. The softening effect had a significant influence on the peak value of the longitudinal residual stress and had little influence on the transverse residual stress. Comparing the numerical simulation results with the experimental results, it could be seen that the calculation results of the welding residual stress were in the best agreement with the experimental measurement results when the solid-state transformation and softening effects were considered at the same time.