bluuebunny/crossref_metadata_2025 huggingface dataset:
A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages
Authors: Richert Iseulys , Berchard Paul , Abbes Lhorra , Novikov Alexey , Chettab Kamel , Vandermoeten Alexandra , Dumontet Charles , Karanian Marie , Kerzerho Jerome , Caroff Martine , Blay Jean-Yves , Dutour Aurélie
Published: September 2023

Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA’s immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA.
The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis
Authors: Napolitano Mariasanta , Siragusa Sergio
Published: September 2023

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.
Using Single-Case Experimental Design and Patient-Reported Outcome Measures to Evaluate the Treatment of Cancer-Related Cognitive Impairment in Clinical Practice
Authors: Ferguson Robert J. , Terhorst Lauren , Gibbons Benjamin , Posluszny Donna M. , Chang Hsuan , Bovbjerg Dana H. , McDonald Brenna C.
Published: September 2023

Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) demonstrated to improve CRCI symptoms and QOL in previous research. The aim of this article is to describe a single-case experimental design (SCED) approach to evaluate interventions for CRCI in clinical practice with patient-reported outcome measures (PROs). We illustrate the use of contemporary SCED methods as a means of evaluating MAAT, or any CRCI treatment, once clinically deployed. With the anticipated growth of cancer survivorship and concurrent growth in the number of survivors with CRCI, the treatment implementation and evaluation methods described here can be one way to assess and continually improve CRCI rehabilitative services.
Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution
Authors: Cheung Elki Sze-Nga , Law Frederick Chun-Him , Fung Nelson Tsz-Cheong , Soong Inda Sung , Hung Rico Hing-Ming , Tse Teddy Ka-Ho , Wong Ken Ka-Shing , Wu Philip Yuguang
Published: September 2023

This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55–57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1–16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity.
Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function
Authors: Belluti Silvia , Imbriano Carol , Casarini Livio
Published: September 2023

Estrogens are almost ubiquitous steroid hormones that are essential for development, metabolism, and reproduction. They exert both genomic and non-genomic action through two nuclear receptors (ERα and ERβ), which are transcription factors with disregulated functions and/or expression in pathological processes. In the 1990s, the discovery of an additional membrane estrogen G-protein-coupled receptor augmented the complexity of this picture. Increasing evidence elucidating the specific molecular mechanisms of action and opposing effects of ERα and Erβ was reported in the context of prostate cancer treatment, where these issues are increasingly investigated. Although new approaches improved the efficacy of clinical therapies thanks to the development of new molecules targeting specifically estrogen receptors and used in combination with immunotherapy, more efforts are needed to overcome the main drawbacks, and resistance events will be a challenge in the coming years. This review summarizes the state-of-the-art on ERα and ERβ mechanisms of action in prostate cancer and promising future therapies.
Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling
Authors: Reynolds Samuel B. , Pettit Kristen , Kandarpa Malathi , Talpaz Moshe , Li Qing
Published: September 2023

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in the absence of JAK2, MPL, and CALR but when clinical, morphologic criteria are met and other mutation(s) is/are present, including ASXL1, EZH2, and SRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response. KRAS and NRAS mutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such as CBL, NF1, BRAF, and PTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence of RAS and related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets.
Correction: Chua et al. Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore. Cancers 2023, 15, 1812
Authors: Chua Brandon , Lim Li Min , Ng Joseph Soon Yau , Ma Yan , Wee Hwee Lin , Caro J. Jaime
Published: September 2023

The authors wish to revise two words in Table 1 row 3, and the first paragraph of Section 2 [...]
Epstein–Barr Virus Infection in Cancer
Authors: Mundo Lucia , Leoncini Lorenzo , Accardi-Gheit Rosita
Published: September 2023

EBV was the first human oncogenic virus identified [...]
t-BuOOH/TiO2 Photocatalytic System as a Convenient Peroxyl Radical Source at Room Temperature under Visible Light and Its Application for the CH-Peroxidation of Barbituric Acids
Authors: Lopat’eva Elena , Krylov Igor , Terent’ev Alexander
Published: September 2023

TiO2 is one of the most promising heterogeneous photoredox catalysts employed in oxidative pollutant destruction, CO2 reduction, water splitting, disinfection, solar cell design and organic synthesis. Due to the wide bandgap of TiO2, visible light energy is not sufficient for its activation, and electron/hole pairs generated upon UV irradiation demonstrate limited selectivity for application in organic synthesis. Thus, the development of TiO2-based catalytic systems activated by visible light is highly attractive. In the present work we demonstrate the generation of t-BuOO• radicals from tert-butylhydroperoxide catalyzed using commercially available unmodified TiO2 under visible light. This finding was used for the highly selective CH-peroxidation of barbituric acids, which contrasts with the behavior of the known TiO2/H2O2/UV photocatalytic system used for deep oxidation of organic pollutants.
Sterical Self-Consistency of Carbonaceous Nanopolyhedra Triggered by Introduced CNTs to Optimize ORR Performance
Authors: Zuo Yuanhui , Tang Yanlong , Shi Huancong , Lu Shijian , Tontiwachwuthikul Paitoon
Published: September 2023

The electrocatalyst of oxygen reduction reactions is one of the basic components of a fuel cell. In addition to costly Pt/C benchmark catalysts, cost-effective carbon-based catalysts have received the most attention. Enormous efforts have been dedicated to trade off the catalyst performance against the economic benefit. Optimizing composition and/or structure is a universal strategy for improving performance, but it is typically limited by tedious synthesis steps. Herein, we have found that directly introducing CNT into MOF-derived carbonaceous nanopolyhedra, i.e., introduced carbon nanotubes (CNTs) penetrated porous nitrogen-doped carbon polyhedra (NCP) dotted with cobalt nanoparticles (denoted as CNTs-Co@NCP), can optimize the catalytic activity, stability, and methanol tolerance. The hierarchical architecture combines the 0D/1D/3D Co/CNT/NCP interfaces and 1D/3D CNT/NCP junctions with the frameworks with a greatly exposed active surface, strengthened mass transport kinetics, stereoscopic electrical conductivity networks and structural robustness. The sterical self-consistency of MOF-self-assembly triggered by introduced CNTs demonstrates tactful ORR electrocatalytic activity regulation. Eventually, the CNTs-Co@NCP showed a half-wave potential (E1/2) of 0.86 V and a diffusion-limited current density (JL) of 5.94 mA/cm2 in alkaline electrolyte. The CNTs-Co@NCP was integrated into the cathode of a direct methanol fuel cell (DMFC) with an anion-exchange membrane, and an open-circuit voltage (OCV) of 0.93 V and a high power density of 46.6 mW cm−2 were achieved. This work successfully developed a catalyst with competitive ORR performance through plain parameter fine-tuning without complex material design.
Altered Epigenetic Marks and Gene Expression in Fetal Brain, and Postnatal Behavioural Disorders, Following Prenatal Exposure of Ogg1 Knockout Mice to Saline or Ethanol
Authors: Bhatia Shama , Bodenstein David , Cheng Ashley P. , Wells Peter G.
Published: September 2023

Oxoguanine glycosylase 1 (OGG1) is widely known to repair the reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG), and more recently was shown to act as an epigenetic modifier. We have previously shown that saline-exposed Ogg1 −/− knockout progeny exhibited learning and memory deficits, which were enhanced by in utero exposure to a single low dose of ethanol (EtOH) in both Ogg1 +/+ and −/− progeny, but more so in Ogg1 −/− progeny. Herein, OGG1-deficient progeny exposed in utero to a single low dose of EtOH or its saline vehicle exhibited OGG1- and/or EtOH-dependent alterations in global histone methylation and acetylation, DNA methylation and gene expression (Tet1 (Tet Methylcytosine Dioxygenase 1), Nlgn3 (Neuroligin 3), Hdac2 (Histone Deacetylase 2), Reln (Reelin) and Esr1 (Estrogen Receptor 1)) in fetal brains, and behavioural changes in open field activity, social interaction and ultrasonic vocalization, but not prepulse inhibition. OGG1- and EtOH-dependent changes in Esr1 and Esr2 mRNA and protein levels were sex-dependent, as was the association of Esr1 gene expression with gene activation mark histone H3 lysine 4 trimethylation (H3K4me3) and gene repression mark histone H3 lysine 27 trimethylation (H3K27me3) measured via ChIP-qPCR. The OGG1-dependent changes in global epigenetic marks and gene/protein expression in fetal brains, and postnatal behavioural changes, observed in both saline- and EtOH-exposed progeny, suggest the involvement of epigenetic mechanisms in developmental disorders mediated by 8-oxoG and/or OGG1. Epigenetic effects of OGG1 may be involved in ESR1-mediated gene regulation, which may be altered by physiological and EtOH-enhanced levels of ROS formation, possibly contributing to sex-dependent developmental disorders observed in Ogg1 knockout mice. The OGG1- and EtOH-dependent associations provide a basis for more comprehensive mechanistic studies to determine the causal involvement of oxidative DNA damage and epigenetic changes in ROS-mediated neurodevelopmental disorders.
Lymphatic Defects in Zebrafish sox18 Mutants Are Exacerbated by Perturbed VEGFC Signaling, While Masked by Elevated sox7 Expression
Authors: Moleri Silvia , Mercurio Sara , Pezzotta Alex , D’Angelo Donatella , Brix Alessia , Plebani Alice , Lini Giulia , Di Fuorti Marialaura , Beltrame Monica
Published: September 2023

Mutations in the transcription factor-coding gene SOX18, the growth factor-coding gene VEGFC and its receptor-coding gene VEGFR3/FLT4 cause primary lymphedema in humans. In mammals, SOX18, together with COUP-TFII/NR2F2, activates the expression of Prox1, a master regulator in lymphatic identity and development. Knockdown studies have also suggested an involvement of Sox18, Coup-tfII/Nr2f2, and Prox1 in zebrafish lymphatic development. Mutants in the corresponding genes initially failed to recapitulate the lymphatic defects observed in morphants. In this paper, we describe a novel zebrafish sox18 mutant allele, sa12315, which behaves as a null. The formation of the lymphatic thoracic duct is affected in sox18 homozygous mutants, but defects are milder in both zygotic and maternal-zygotic sox18 mutants than in sox18 morphants. Remarkably, in sox18 mutants, the expression of the closely related sox7 gene is elevated where lymphatic precursors arise. Sox7 could thus mask the absence of a functional Sox18 protein and account for the mild lymphatic phenotype in sox18 mutants, as shown in mice. Partial knockdown of vegfc exacerbates lymphatic defects in sox18 mutants, making them visible in heterozygotes. Our data thus reinforce the genetic interaction between Sox18 and Vegfc in lymphatic development, previously suggested by knockdown studies, and highlight the ability of Sox7 to compensate for Sox18 lymphatic dysfunction.
Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model
Authors: Fu Ru-Huei , Hong Syuan-Yu , Chen Hui-Jye
Published: September 2023

Defective autophagy is one of the cellular hallmarks of Parkinson’s disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of Acanthopanax senticosus. It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in C. elegans, degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome–lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting SIRT1. The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD.
The Chemical Inhibitors of Endocytosis: From Mechanisms to Potential Clinical Applications
Authors: Szewczyk-Roszczenko Olga Klaudia , Roszczenko Piotr , Shmakova Anna , Finiuk Nataliya , Holota Serhii , Lesyk Roman , Bielawska Anna , Vassetzky Yegor , Bielawski Krzysztof
Published: September 2023

Endocytosis is one of the major ways cells communicate with their environment. This process is frequently hijacked by pathogens. Endocytosis also participates in the oncogenic transformation. Here, we review the approaches to inhibit endocytosis, discuss chemical inhibitors of this process, and discuss potential clinical applications of the endocytosis inhibitors.
Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions
Authors: Hung Kuang-Chen , Tien Ni , Bau Da-Tian , Yao Chun-Hsu , Chen Chan-Hung , Yang Jiun-Long , Lin Meng-Liang , Chen Shih-Shun
Published: September 2023

The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)−GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)−protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells. The use of lethal-7g (let-7g) mimic and let-7g inhibitor confirmed that elevated let-7g resulted in a decrease in KRAS expression, which attenuated the PI3K−Rac1−Akt−BCL-2/BCL-xL-modulated mitochondrial energy metabolic functions. Increased let-7g depends on the suppression of the RNA-specificity of monocyte chemoattractant protein-induced protein-1 (MCPIP1) ribonuclease since NGN specifically blocks the degradation of pre-let-7g by NPC cell-derived immunoprecipitated MCPIP1. Converging lines of evidence indicate that the inhibition of MCPIP1 by NGN leads to let-7g upregulation, suppressing oncogenic KRAS-modulated PI3K–Rac1–Akt signaling and thereby impeding the metabolic activities of aerobic glycolysis and mitochondrial OXPHOS.
Inborn Errors of Metabolism with Ataxia: Current and Future Treatment Options
Authors: Bremova-Ertl Tatiana , Hofmann Jan , Stucki Janine , Vossenkaul Anja , Gautschi Matthias
Published: September 2023

A number of hereditary ataxias are caused by inborn errors of metabolism (IEM), most of which are highly heterogeneous in their clinical presentation. Prompt diagnosis is important because disease-specific therapies may be available. In this review, we offer a comprehensive overview of metabolic ataxias summarized by disease, highlighting novel clinical trials and emerging therapies with a particular emphasis on first-in-human gene therapies. We present disease-specific treatments if they exist and review the current evidence for symptomatic treatments of these highly heterogeneous diseases (where cerebellar ataxia is part of their phenotype) that aim to improve the disease burden and enhance quality of life. In general, a multimodal and holistic approach to the treatment of cerebellar ataxia, irrespective of etiology, is necessary to offer the best medical care. Physical therapy and speech and occupational therapy are obligatory. Genetic counseling is essential for making informed decisions about family planning.
Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells
Authors: Sporkova Alexandra , Nahar Taslima , Cao Mingsi , Ghosh Subhajit , Sens-Albert Carla , Friede Prisca Amayi Patricia , Nagel Anika , Al-Hasani Jaafar , Hecker Markus
Published: September 2023

In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11–Isl1–Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.
Differential Effects of Regulatory T Cells in the Meninges and Spinal Cord of Male and Female Mice with Neuropathic Pain
Authors: Fiore Nathan T. , Keating Brooke A. , Chen Yuting , Williams Sarah I. , Moalem-Taylor Gila
Published: September 2023

Immune cells play a critical role in promoting neuroinflammation and the development of neuropathic pain. However, some subsets of immune cells are essential for pain resolution. Among them are regulatory T cells (Tregs), a specialised subpopulation of T cells that limit excessive immune responses and preserve immune homeostasis. In this study, we utilised intrathecal adoptive transfer of activated Tregs in male and female mice after peripheral nerve injury to investigate Treg migration and whether Treg-mediated suppression of pain behaviours is associated with changes in peripheral immune cell populations in lymphoid and meningeal tissues and spinal microglial and astrocyte reactivity and phenotypes. Treatment with Tregs suppressed mechanical pain hypersensitivity and improved changes in exploratory behaviours after chronic constriction injury (CCI) of the sciatic nerve in both male and female mice. The injected Treg cells were detected in the choroid plexus and the pia mater and in peripheral lymphoid organs in both male and female recipient mice. Nonetheless, Treg treatment resulted in differential changes in meningeal and lymph node immune cell profiles in male and female mice. Moreover, in male mice, adoptive transfer of Tregs ameliorated the CCI-induced increase in microglia reactivity and inflammatory phenotypic shift, increasing M2-like phenotypic markers and attenuating astrocyte reactivity and neurotoxic astrocytes. Contrastingly, in CCI female mice, Treg injection increased astrocyte reactivity and neuroprotective astrocytes. These findings show that the adoptive transfer of Tregs modulates meningeal and peripheral immunity, as well as spinal glial populations, and alleviates neuropathic pain, potentially through different mechanisms in males and females.
Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View
Authors: Sanghai Nitesh , Tranmer Geoffrey K.
Published: September 2023

Neurodegenerative diseases (NDDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.
TRPV1 Channels Are New Players in the Reticulum–Mitochondria Ca2+ Coupling in a Rat Cardiomyoblast Cell Line
Authors: Tessier Nolwenn , Ducrozet Mallory , Dia Maya , Badawi Sally , Chouabe Christophe , Crola Da Silva Claire , Ovize Michel , Bidaux Gabriel , Van Coppenolle Fabien , Ducreux Sylvie
Published: September 2023

The Ca2+ release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca2+ homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential vanilloid 1 (TRPV1), a Ca2+-permeable ion channel and a polymodal nociceptor. We found TRPV1 channels in the reticular membrane, including some at MAMs, in a rat cardiomyoblast cell line (SV40-transformed H9c2) by Western blotting, immunostaining, cell fractionation, and proximity ligation assay. We used chemical and genetic probes to perform Ca2+ imaging in four cellular compartments: the endoplasmic reticulum (ER), cytoplasm, mitochondrial matrix, and mitochondrial surface. Our results showed that the ER Ca2+ released through TRPV1 channels is detected at the mitochondrial outer membrane and transferred to the mitochondria. Finally, we observed that prolonged TRPV1 modulation for 30 min alters the intracellular Ca2+ equilibrium and influences the MAM structure or the hypoxia/reoxygenation-induced cell death. Thus, our study provides the first evidence that TRPV1 channels contribute to MAM Ca2+ exchanges.
Establishment and Characterization of Continuous Satellite Muscle Cells from Olive Flounder (Paralichthys olivaceus): Isolation, Culture Conditions, and Myogenic Protein Expression
Authors: Krishnan Sathish , Ulagesan Selvakumari , Cadangin Josel , Lee Ji-Hye , Nam Taek-Jeong , Choi Youn-Hee
Published: September 2023

Olive flounder (Paralichthys olivaceus) muscle satellite cells (OFMCs) were obtained by enzymatic primary cell isolation and the explant method. Enzymatic isolation yielded cells that reached 80% confluence within 8 days, compared to 15 days for the explant method. Optimal OFMC growth was observed in 20% fetal bovine serum at 28 °C with 0.8 mM CaCl2 and the basic fibroblast growth factor (BFGF) to enhance cell growth. OFMCs have become permanent cell lines through the spontaneous immortalization crisis at the 20th passage. Olive flounder skeletal muscle myoblasts were induced into a mitogen-poor medium containing 2% horse serum for differentiation; they fused to form multinucleate myotubes. The results indicated complete differentiation of myoblasts into myotubes; we also detected the expression of the myogenic regulatory factors myoD, myogenin, and desmin. Upregulation (Myogenin, desmin) and downregulation (MyoD) of muscle regulation factors confirmed the differentiation in OFMCs.
Comics as a Physical Education Tool for Health Promotion in Brazilian Primary Education, Based on Paulo Freire’s Principles of Empowerment
Authors: Nascimento George Bernard Soares , de Maio Nascimento Marcelo , de Araújo Luciana Márcia Gomes , Gouveia Élvio R. , Ihle Andreas
Published: September 2023

Incorrect postural habits developed already at an early age are predictors of low back pain and functional limitations in adult life. Postural education programs (PEPs) are activities developed in Physical Education classes with the aim of promoting healthy habits. One tool used by PEPs is comics. The objective of this study was to develop comics and apply them as a teaching tool in PEPs for students aged seven to ten years. The procedures were based on individual empowerment principles, including creation activities, reading, painting, crosswords, and discussion of comics. The activities strengthened the students’ interactions, gaining new knowledge that required cognitive and expressive resources to interpret, associate, and conceptualize themes of correct body posture. During six weeks of intervention, knowledge about body posture, anatomy, and health promotion exercises increased significantly in relation to the beginning of activities. The comic book proved to be an effective, attractive, and low-cost didactic resource.
Wearing Resistance of Metal Coating Layers after Laser Beam Heat Treatment
Authors: Oláh Arthur , Machedon-Pisu Teodor , Vizureanu Petrică
Published: September 2023

Laser heat treatment (LHT) is applied herein after coating. Evaluation of the results was performed by studying the microstructures via metallographic SEM/EDX microscopy, and the mechanical properties were analyzed in terms of microscopic hardness and abrasion resistance. The objective of this study was to investigate the effect of LHT on the wear resistance of metal coatings. The results indicate the influence of the microstructure and chemical composition of the electrodes on the microhardness and wear resistance of the metal coatings (MCs).
The Effect of Water-Based Primer Pretreatment on the Performance of Water-Based Inkjet Coatings on Wood Surfaces
Authors: Sang Ruijuan , Yang Fei , Fan Zhenxian
Published: September 2023

Wood surface staining suffers from volatile organic gas (VOC) emissions and uneven staining at knots, and these environmental and decorative performance issues are the main restrictions in the application of wood products, indoors and outdoors. Herein, the method of wood-based panel surface staining is presented for improving environmental and decorative performance using environmentally friendly water-based inks, water-based primers, and digital inkjet coloring technology. The wood-based panels’ dye coatings were prepared with oak plank as the sample substrate, a one-component water-based primer as the interfacial adhesive, and a water-based ink as a coating agent. The application amount of water-based primer was 15 g per square meter, applied twice by a roller, and the coating thickness reached approximately 20 μm. The influence of the one-component water-based primer on the interfacial properties of water-based inkjet coatings was investigated via Fourier-transform infrared (FTIR) spectroscopy, a video contact angle analyzer, and environmental scanning electron microscopy (SEM). The results showed that the one-component water-based primer connected the plain board to the inkjet-printed coating. The addition of a water-based primer coating reduced the contact angle of the wood surface from 41.69° to 37.28° and increased wettability. This helped enhance the adhesion of the water-based inkjet coating, and the primer treatment in the semi-closed state covered the scar defects of the plain board while preserving the path of grain holes on the wood surface. With image editing and inkjet dyeing, the surface of the oak plank obtained a uniform staining effect on the primer coating while maintaining the original natural pore texture of the wood. This study proves that a one-component water-based primer pretreatment process for water-based inkjet printing coatings on wood surfaces has excellent modification ability and interface adhesion. It provides a feasible method of color modification for artificial panel surfaces.
Assessment of Mechanical and Tribological Behavior of AA6061 Reinforced with B4C and Gr Hybrid Metal Matrix Composites
Authors: Yunus Mohammed , Alfattani Rami
Published: September 2023

Aluminum alloy (AA6061)-based hybrid metal matrix composites (HMMCs) are manufactured using a dual stir casting method, with varying volume percentages of B4C (5%, 10%, and 15%) and Gr (10%, 15%, and 20%) incorporated. The resulting HMMC and reinforcement elements are uniformly dispersed within the main matrix, forming a mechanically mixed layer with interfacial reactions. This layer reduces wear loss and friction coefficient compared to AA6061, especially with higher amounts of B4C and Gr, as they demonstrate little aggregation of reinforced material. The presence of Gr particles enabled the impact of different wear parameters (applied load, sliding speed, and distance) to be combined. Micro-hardness studies demonstrate that the hardness of HMMC increases as the volume fraction of reinforced particles and sliding distance increase. The compression test revealed a 22% improvement over AA6061. As a result, adding reinforcing materials to the matrix contributes to inducing greater strength by increasing wear resistance with a Gr-imparted lubrication effect.
Influence of Bilayer Thickness on Mechanical and Tribological Properties of (Ti-Al)N/MoN Nanostructured Hard Coatings Deposited by Cathodic Arc Ion Plating
Authors: Yousaf Muhammad I. , Abudouwufu Tushagu , Yang Bing , Tolstoguzov Alexander , Fu Dejun
Published: September 2023

Deposition of (Ti-Al)N/MoN multilayered coatings was carried out through a cathodic ion-plating system in an argon and then nitrogen atmosphere. Bilayer thickness (Λ) of all the samples were achieved, from 22 to 104 nm, by organizing substrate holder rotational speed (SRS). To obtain the optimum properties of the (Ti-Al)N/MoN coatings, the Ti and Al ratio was maintained at a level of 1:1. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy were utilized to analyze the crystal structure and morphology of the coatings. Mechanical and tribological properties were examined by nanohardness and atomic force microscopy (AFM). The preferred orientation of the (Ti-Al)N/MoN nanoscale multilayer films was TiAlN (200) and MoN (200), which had face centered cubic (fcc) and hexagonal structures, respectively. The hardness increased with the decrease in Λ (104 nm to 26 nm), and then it increased. The highest hardness of 37 GPa was revealed at Λ = 26 nm, whereas the least wear rate of 8.09 × 10−7 mm3/N.m was attained at Λ = 22 nm. Wear rate, roughness, and coefficient of friction were decreased with decreasing bilayer period. EDS results showed that Al and Ti contents were almost the same in all samples, as per design of the experiment.
A Novel and Secure Fake-Modulus Based Rabin-Ӡ Cryptosystem
Authors: Ramesh Raghunandan , Dodmane Radhakrishna , Shetty Surendra , Aithal Ganesh , Sahu Monalisa , Sahu Aditya
Published: September 2023

Electronic commerce (E-commerce) transactions require secure communication to protect sensitive information such as credit card numbers, personal identification, and financial data from unauthorized access and fraud. Encryption using public key cryptography is essential to ensure secure electronic commerce transactions. RSA and Rabin cryptosystem algorithms are widely used public key cryptography techniques, and their security is based on the assumption that it is computationally infeasible to factorize the product of two large prime numbers into its constituent primes. However, existing variants of RSA and Rabin cryptosystems suffer from issues like high computational complexity, low speed, and vulnerability to factorization attacks. To overcome the issue, this article proposes a new method that introduces the concept of fake-modulus during encryption. The proposed method aims to increase the security of the Rabin cryptosystem by introducing a fake-modulus during encryption, which is used to confuse attackers who attempt to factorize the public key. The fake-modulus is added to the original modulus during encryption, and the attacker is unable to distinguish between the two. As a result, the attacker is unable to factorize the public key and cannot access the sensitive information transmitted during electronic commerce transactions. The proposed method’s performance is evaluated using qualitative and quantitative measures. Qualitative measures such as visual analysis and histogram analysis are used to evaluate the proposed system’s quality. To quantify the performance of the proposed method, the entropy of a number of occurrences for the pixels of cipher text and differential analysis of plaintext and cipher text is used. When the proposed method’s complexity is compared to a recent variant of the Rabin cryptosystem, it can be seen that it is more complex to break the proposed method—represented as O(ɲ× τ) which is higher than Rabin-P (O(ɲ)) algorithms.
Development of Cerium Oxide/Chitosan/Graphene Oxide Nanocomposite: An Investigation toward Its Biological Applications under In Vitro Conditions
Authors: Saranya J. , Preethi S. , Shaik Mohammed Rafi , Khan Merajuddin , Khan Mujeeb , Shaik Baji
Published: September 2023

A ternary nanocomposite was prepared using cerium oxide, chitosan, and graphene oxide (CeO2/CS/GO) using a simple and cost-effective wet chemical method. The physicochemical properties of the developed ternary nanocomposite were examined using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and ultraviolet-visible spectroscopy. Furthermore, the therapeutic behavior of the developed CeO2/CS/GO composite was assessed using anti-bacterial, anti-fungal, and anti-cancer assays. For Escherichia coli, Staphylococcus aureus, and Salmonella species, 750 µg/mL of the CeO2/CS/GO composite showed effective anti-bacterial activity, with a zone of inhibition of 9 mm. Additionally, the CeO2/CS/GO composite’s anti-fungal activity against Aspergillus niger was studied. The anti-cancer properties of different concentrations of the CeO2/CS/GO composite were assessed on MCF-7 cells, and 18.8% of cells were found to be viable at the maximum concentration of 1000 µg/mL CeO2/CS/GO and 46.37% at 125 µg/mL. The results of the hemolysis assay performed using human red blood cells and various concentrations of the CeO2/CS/GO composite indicated that the nanocomposite possesses biological properties. Overall, it can act as a therapeutic platform for breast cancer, bacterial and fungal infections.
Design and Performance Enhancement of a Piezoelectric Micromachined Ultrasonic Transducer Based on NBBT Lead-Free Piezoelectric Single-Crystal Thin Film
Authors: Liu Yaqi , Zhang Qiaozhen , Chen Mingzhu , Liu Xiaonan , Yang Jiye , Wang Feifei , Tang Yanxue , Miao Bin , Li Jiadong , Zhao Xiangyong
Published: September 2023

Piezoelectric micromachined ultrasonic transducers (PMUTs) have attracted widespread attention due to their high performance, miniaturization, and easy integration with semiconductor processes. In this paper, a PMUT device based on high-performance and lead-free Na0.5Bi0.5TiO3-BaTiO3 (NBBT) piezoelectric single-crystal thin films was designed for the application of medical high-frequency ultrasonics. Three-dimensional modeling and analysis of PMUT elements on the proposed structure were performed via the finite element method. The relationship between structure configuration in terms of the top electrode and the cavity shape of the bottom was studied. The PMUT properties and its device performance, including resonant frequency, effective electromechanical coupling factor (keff2), and the static sensitivity of different device structures, were analyzed. In addition, by rotating the Euler Angle γ of the NBBT piezoelectric single-crystal film, the static sensitivity and keff2 of the model are improved to 1.34 when γ  is rotated to 45 ± 5°. It was shown that the PMUT using rotated NBBT demonstrated an enhanced relative pulse-echo sensitivity of −46 dB and a bandwidth of 35% when the reflective surface was 200 μm. We conclude that the PMUT in accordance with an NBBT piezoelectric single-crystal film designed by simulation offers a high frequency, larger keff2, and high sensitivity, which provides application prospects in high-resolution and high-frequency medical ultrasonic imaging.
SLEEPexpert+: Blending Internet-Based Cognitive Behavioral Therapy for Insomnia with In-Person Psychotherapy—A Feasibility Study in Routine Care
Authors: Schmid Daniel , Duss Simone , Hertenstein Elisabeth , Nissen Christoph , Schneider Carlotta , Urech Antoine , Vorster Albrecht , Berger Thomas
Published: September 2023

Insomnia is characterized by frequent and persistent difficulties initiating and maintaining sleep, along with impaired daytime functioning. Blended treatments are increasingly popular for treating psychological disorders such as depression. Blended treatments combine elements of face-to-face therapy and online interventions. A single-arm pre-post study investigated the feasibility of a blended treatment combining face-to-face cognitive behavioral therapy for insomnia and internet-based cognitive behavioral therapy for insomnia (SLEEPexpert+). The findings show that the therapists have a positive attitude toward blended CBT-I (b-CBT-I) and that they feel supported by the online components of the treatment. Possible barriers to implementing blended treatments are integrating the online materials into the face-to-face sessions and adapting one’s therapeutic style to the blended treatment approach. No definitive statements about the effectiveness of the b-CBT-I treatment can be made. However, of the six presented cases, five patients showed notably higher sleep efficiency and fewer insomnia symptoms at the end of the therapy. Program usage data indicate that participants mainly used the online components at the beginning of their treatment. Future studies should investigate the effectiveness of b-CBT-I with a sufficiently powered randomized controlled trial comparing b-CBT-I with an adequate control group in routine care.
Serum Phosphorus, Serum Bicarbonate, and Renal Function in Relation to Liver CYP1A2 Activity
Authors: Ito Joy , Lemus Hector , Wu Tianying
Published: September 2023

The liver plays an important role in normal metabolism and physiological functions such as acid-base balance; however, limited epidemiologic studies have investigated how the liver contributes toward acid-base balance using non-invasive biomarkers. We determined associations between serum biomarkers related to acid-base balance and renal function with liver CYP1A2 activity. We used data from 1381 participants of the 2009–2010 National Health and Nutrition Examination Survey (NHANES) with measurements of serum phosphorus, serum bicarbonate, caffeine intake, caffeine metabolites, and estimated glomerular filtration rate (eGFR). Liver CYP1A2 activity was estimated using urine caffeine metabolite indices, which were calculated as the ratio of one of the urine caffeine metabolites (i.e., paraxanthine and 1-methyluric acid) to caffeine intake. We analyzed associations in the whole data set and in different strata of hepatic steatosis index (HSI) based on different cut-points. We found that serum bicarbonate was positively associated with CYP1A2 activity in the whole data set when comparing persons with bicarbonate at Q4 to Q1 (β = 0.18, p = 0.10 for paraxanthine; β = 0.20, p = 0.02 for 1-methyluric acid). Furthermore, serum phosphorus was positively associated with CYP1A2 activity only in the stratum of 30 ≤ HSI < 36. Lastly, low eGFR was significantly associated with lower CYP1A2 activity measured with paraxanthine in the whole dataset and in all the strata with HSI < 42; when comparing eGFR < 60 to eGFR > 90, β estimates ranged from −0.41 to −1.38, p-values ranged from 0.0018 to 0.004. We observed an opposite trend in the highest stratum (HSI ≥ 42). Non-invasive measurements of serum bicarbonate, serum phosphorus, and eGFR have dynamic associations with CYP1A2 activity. These associations depend on the extent of liver damage and the caffeine metabolite used to assess CYP1A2 activity.