bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Thermoelectric Responses of a Conductive Semi-Solid Surface to Variable Thermal Shock in the Context of the Moore–Gibson–Thompson Thermoelasticity
Authors: Megahid Sami F. , Abouelregal Ahmed E. , Askar Sameh S. , Marin Marin
Published: July 2023

In this study, the Moore–Gibson–Thompson (MGT) concept of thermal conductivity is applied to a two-dimensional elastic solid in the form of a half-space. This model was constructed using Green and Naghdi’s thermoelastic model to address the infinite velocity problem of heat waves. It has been taken into account that the free surface of the medium is immersed in an electromagnetic field of constant intensity, undergoes thermal shock, and rotates with a uniform angular velocity. The governing equations of a modified version of Ohm’s law account for the impact of temperature gradients and charge densities. By using the method of normal mode analysis, an analytical representation of the studied physical fields was obtained. The effect of rotation and the modulus of modified Ohm’s law on the responses of the field distributions examined is discussed, along with accompanying graphical representations. Other thermoelastic models have been compared with the results of the proposed system when the relaxation time is ignored.
Research Progress on Iron-Based Materials for Aqueous Sodium-Ion Batteries
Authors: Chang Songyang , Qiu Shen , Katiyar Swati , Florez Gomez Jose Fernando , Feng Zhenxing , Wu Xianyong
Published: July 2023

Aqueous sodium-ion batteries (ASIBs) represent a promising battery technology for stationary energy storage, due to their attractive merits of low cost, high abundance, and inherent safety. Recently, a variety of advanced cathode, anode, and electrolyte materials have been developed for ASIBs, which not only enhance our fundamental understanding of the Na insertion mechanism, but also facilitate the research and development of practical ASIB systems. Among these electrode materials, iron-based materials are of particular importance because of the high abundance, low price, and low toxicity of Fe elements. However, to our knowledge, there are no review papers that specifically discuss the properties of Fe-based materials for ASIBs yet. In this review, we present the recent research progress on Fe-based cathode/anode materials, which include polyanionic compounds, Prussian blue, oxides, carbides, and selenides. We also discuss the research efforts to build Fe-based ASIB full cells. Lastly, we share our perspectives on the key challenges that need to be addressed and suggest alternative directions for aqueous Na-ion batteries. We hope this review paper can promote more research efforts on the development of low-cost and low-toxicity materials for aqueous battery applications.
Anion and Cation Co-Modified Vanadium Oxide for Cathode Material of Aqueous Zinc-Ion Battery
Authors: Zhang Xueqi , Bian Ruilin , Sang Zhiyuan , Tan Shandong , Liang Ji , Wang Liqun , Hou Feng
Published: July 2023

Aqueous zinc-ion batteries (ZIBs) have been regarded as a promising alternative to traditional lithium-based batteries due to their intrinsic advantages of safety, low cost, and abundance. However, the strong electrostatic interaction between Zn2+ and the layer-structured cathodes is still a key issue that hinders the batteries from storing more Zn. Herein, we report partially nitrided and cation-doped vanadium oxide for improved Zn storage performance. Specifically, the defects and nitride species that are generated inside the material upon nitriding improve the conductivity of the material and introduce a new Zn storage mechanism. The intercalation of cations, in contrast, widens the interlayer spacing to store more Zn2+ ions and enhances the cycling stability of the material. These merits synergistically lead to significantly enhanced electrochemical Zn2+ ion storage performance, in terms of a high specific capacity of 418.5 mAh·g−1 at a current density of 0.1 A·g−1 and a capacity retention of 81.2% after 500 cycles at 2.0 A·g−1. The new modification strategy for V2O5 suggested in this work could provide insight into the development of high-performance ZIBs.
Cepabiflas B and C as Novel Anti-Inflammatory and Anti-Apoptotic Agents against Endotoxin-Induced Acute Kidney and Hepatic Injury in Mice: Impact on Bax/Bcl2 and Nrf2/NF-κB Signalling Pathways
Authors: Rizq Akaber T. , Sirwi Alaa , El-Agamy Dina S. , Abdallah Hossam M. , Ibrahim Sabrin R. M. , Mohamed Gamal A.
Published: July 2023

Cepabiflas B and C (CBs) are flavonoid dimers separated from Allium cepa. They demonstrated antioxidant and α-glucosidase and protein tyrosine phosphatase 1B inhibition capacities. However, their anti-inflammatory activities and their effects on endotoxemia are unknown. The current study aimed at exploring the protective activities of CBs on lipopolysaccharide (LPS)-induced kidney and liver damage in mice and investigating the possible molecular mechanisms. Mice were orally treated with a low (40 mg/kg) or high (60 mg/kg) dose of CBs for five days prior to a single intraperitoneal injection of LPS (10 mg/kg). Samples of serum and hepatic and kidney tissues were collected 24 h after the LPS challenge. Changes in serum indices of hepatic and renal injury, pathological changes, molecular biological parameters, and proteins/genes related to inflammation and apoptosis of these organs were estimated. LPS injection resulted in deleterious injury to both organs as indicated by elevation of serum ALT, AST, creatinine, and BUN. The deteriorated histopathology of hepatic and renal tissues confirmed the biochemical indices. CBs treated groups showed a reduction in these parameters and improved histopathological injurious effects of LPS. LPS-induced hepatorenal injury was linked to elevated oxidative stress as indicated by high levels of MDA, 4-HNE, as well as repressed antioxidants (TAC, SOD, and GSH) in hepatic and kidney tissues. This was accompanied with suppressed Nrf2/HO-1 activity. Additionally, there was a remarkable inflammatory response in both organs as NF-κB signalling was activated and high levels of downstream cytokines were produced following the LPS challenge. Apoptotic changes were observed as the level and gene expression of Bax and caspase-3 were elevated along with declined level and gene expression of Bcl2. Interestingly, CBs reversed all these molecular and genetic changes and restricted oxidative inflammatory and apoptotic parameters after LPS-injection. Collectedly, our findings suggested the marked anti-inflammatory and anti-apoptotic activity of CBs which encouraged its use as a new candidate for septic patients.
TIME Is Ticking for Cervical Cancer
Authors: Kumar Vijay , Bauer Caitlin , Stewart John H.
Published: July 2023

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different immune cells comprising CC TIME and their targeting as future therapeutic approaches.
Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue
Authors: Han Dingding , Huang Ziyang , Rahimi Ehsan , Ardekani Arezoo M.
Published: July 2023

Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. An improved Kedem–Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. At last, the effect of different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. In this paper, we provide a novel and time-efficient computational model for solute transport across the lymphatic vasculature connecting the microscopic properties of the lymphatic vessel membrane to the macroscopic drug absorption.
Breaking Bad: Inflammasome Activation by Respiratory Viruses
Authors: Cerato Julia A. , da Silva Emanuelle F. , Porto Barbara N.
Published: July 2023

The nucleotide-binding domain leucine-rich repeat-containing receptor (NLR) family is a group of intracellular sensors activated in response to harmful stimuli, such as invading pathogens. Some NLR family members form large multiprotein complexes known as inflammasomes, acting as a platform for activating the caspase-1-induced canonical inflammatory pathway. The canonical inflammasome pathway triggers the secretion of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 by the rapid rupture of the plasma cell membrane, subsequently causing an inflammatory cell death program known as pyroptosis, thereby halting viral replication and removing infected cells. Recent studies have highlighted the importance of inflammasome activation in the response against respiratory viral infections, such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While inflammasome activity can contribute to the resolution of respiratory virus infections, dysregulated inflammasome activity can also exacerbate immunopathology, leading to tissue damage and hyperinflammation. In this review, we summarize how different respiratory viruses trigger inflammasome pathways and what harmful effects the inflammasome exerts along with its antiviral immune response during viral infection in the lungs. By understanding the crosstalk between invading pathogens and inflammasome regulation, new therapeutic strategies can be exploited to improve the outcomes of respiratory viral infections.
Corin Deficiency Diminishes Intestinal Sodium Excretion in Mice
Authors: Gu Xiabing , Wang Kun , Li Wenguo , He Meiling , Zhou Tiantian , Liu Meng , Wu Qingyu , Dong Ningzheng
Published: July 2023

Sodium excretion, a critical process in sodium homeostasis, occurs in many tissues, including the kidney and intestine. Unlike in the kidney, the hormonal regulation of intestinal sodium excretion remains unclear. Atrial natriuretic peptide (ANP) is a crucial hormone in renal natriuresis. Corin is a protease critical for ANP activation. Corin and ANP are expressed mainly in the heart. In this study, we investigated corin, ANP, and natriuretic peptide receptor A (Npra) expression in mouse intestines. Corin and ANP expression was co-localized in enteroendocrine cells, whereas Npra expression was on the luminal epithelial cells. In Corin knockout (KO) mice, fecal Na+ and Cl− excretion decreased compared with that in wild-type (WT) mice. Such a decrease was not found in conditional Corin KO mice lacking cardiac corin selectively. In kidney conditional Corin KO mice lacking renal corin, fecal Na+ and Cl− excretion increased, compared to that in WT mice. When WT, Corin KO, and the kidney conditional KO mice were treated with aldosterone, the differences in fecal Na+ and Cl− levels disappeared. These results suggest that intestinal corin may promote fecal sodium excretion in a paracrine mechanism independent of the cardiac corin function. The increased fecal sodium excretion in the kidney conditional Corin KO mice likely reflected an intestinal compensatory response to renal corin deficiency. Our results also suggest that intestinal corin activity may antagonize aldosterone action in the promotion of fecal sodium excretion. These findings help us understand the hormonal mechanism controlling sodium excretion the intestinal tract.
Impacts of Strong ENSO Events on Fish Communities in an Overexploited Ecosystem in the South China Sea
Authors: Li Miao , Xu Youwei , Sun Mingshuai , Li Jiajun , Zhou Xingxing , Chen Zuozhi , Zhang Kui
Published: July 2023

To better understand how fish communities respond to environmental changes under extreme climate events, we examine changes in fish communities in Beibu Gulf during strong El Niño and La Niña events. Strong La Niña and El Niño events affect the composition, abundance, and distribution of fish communities in Beibu Gulf. Fish community distribution and composition change before and after La Niña and El Niño events, and dominant species within them change with stable fishing intensity. The abundance and distribution of small pelagic fish such as Japanese jack mackerel (Trachurus japonicus) and Japanese scad (Decapterus maruadsi) are the most affected. Using a generalized additive model (GAM), we explore relationships between the abundance of T. japonicus and D. maruadsi and a suite of environmental variables. The GAM results revealed that sea surface salinity and sea surface temperature best explain changes in catch per unit effort of these two species during a La Niña event; depth, sea surface temperature, and mixed layer depth during an El Niño event. The results obtained in this study will offer support for implementing more-accurate, scientific fisheries management measures.
Identification of Gene Markers Associated with COVID-19 Severity and Recovery in Different Immune Cell Subtypes
Authors: Ren Jing-Xin , Gao Qian , Zhou Xiao-Chao , Chen Lei , Guo Wei , Feng Kai-Yan , Lu Lin , Huang Tao , Cai Yu-Dong
Published: July 2023

As COVID-19 develops, dynamic changes occur in the patient’s immune system. Changes in molecular levels in different immune cells can reflect the course of COVID-19. This study aims to uncover the molecular characteristics of different immune cell subpopulations at different stages of COVID-19. We designed a machine learning workflow to analyze scRNA-seq data of three immune cell types (B, T, and myeloid cells) in four levels of COVID-19 severity/outcome. The datasets for three cell types included 403,700 B-cell, 634,595 T-cell, and 346,547 myeloid cell samples. Each cell subtype was divided into four groups, control, convalescence, progression mild/moderate, and progression severe/critical, and each immune cell contained 27,943 gene features. A feature analysis procedure was applied to the data of each cell type. Irrelevant features were first excluded according to their relevance to the target variable measured by mutual information. Then, four ranking algorithms (last absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and max-relevance and min-redundancy) were adopted to analyze the remaining features, resulting in four feature lists. These lists were fed into the incremental feature selection, incorporating three classification algorithms (decision tree, k-nearest neighbor, and random forest) to extract key gene features and construct classifiers with superior performance. The results confirmed that genes such as PFN1, RPS26, and FTH1 played important roles in SARS-CoV-2 infection. These findings provide a useful reference for the understanding of the ongoing effect of COVID-19 development on the immune system.
Parathyroid Hormone Related Protein (PTHrP)-Associated Molecular Signatures in Tissue Differentiation and Non-Tumoral Diseases
Authors: Librizzi Mariangela , Naselli Flores , Abruscato Giulia , Luparello Claudio , Caradonna Fabio
Published: July 2023

Parathyroid-hormone-related protein (PTHrP) is encoded by the PTHLH gene which, via alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141, and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, mid-region (containing a nuclear/nucleolar targeting signal), and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation, and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated, or nontumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous, and skin tissues, as well as intestinal, renal, hepatic, pulmonary, and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis-, and diabetes-related changes as diseased states. When reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination are also briefly described.
Biorefinery Development Based on Brewers’ Spent Grain (BSG) Conversion: A Forecasting Technology Study in the Brazilian Scenario
Authors: Evaristo Rafael Benjamin Werneburg , Costa Andréia Alves , Nascimento Paulo Gustavo Barboni Dantas , Ghesti Grace Ferreira
Published: July 2023

Brewers’ spent grain (BSG) is an important waste produced by beer companies and has a high potential to be transformed into commercial by-products. The present paper reports a forecasting technology study with the aid of bibliographic review and patent analysis tools aiming to investigate the maturity of certain technologies, considering the use of BSG on a closed-loop biorefinery and circular bioeconomy concept integrated into a brewery. To evaluate the possibilities of production of high-added-value products in Brazil, we present an overview of BSG’s scientific, technological, and marketing products and applications. The comparison between the numbers of articles versus patents shows that the solutions proposed by research articles are not being transformed into maturated viable technologies. The results suggest that there is a gap between the scientific research in the institutions and their applications in the industry, which lead to the destination of BSG for more economically attractive investments when compared with research in Brazil. Ultimately, from the carried-out analysis, it is possible to propose a brewing process connected to the biorefinery system, showing its possibility in the newly arising brewery industries.
Novel Dual Incretin Receptor Agonists in the Spectrum of Metabolic Diseases with a Focus on Tirzepatide: Real Game-Changers or Great Expectations? A Narrative Review
Authors: Liarakos Alexandros Leonidas , Koliaki Chrysi
Published: July 2023

The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. Tirzepatide is a novel dual incretin receptor agonist (twincretin) that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. The aim of this narrative review was to examine the impact of novel twincretins, focusing on tirzepatide, on the management of a wide spectrum of metabolic diseases. Data from preclinical and clinical trials have shown that twincretins significantly reduce blood glucose levels in T2D, and tirzepatide is the first agent of this class that has been approved for the management of T2D. Additionally, the beneficial impact of tirzepatide on weight reduction has been corroborated in several studies, showing that this agent can achieve substantial and sustained weight loss in obese patients with or without T2D. Data also suggest that tirzepatide could be a promising drug for hepatic steatosis reduction in individuals with NAFLD. The remarkable effects of tirzepatide on glycaemic control, weight loss and liver-related outcomes have posed new research questions that are likely to lead to further advancements in the treatment of T2D, obesity and related metabolic disorders.
Searching for Novel Biomarkers in Thymic Epithelial Tumors: Immunohistochemical Evaluation of Hippo Pathway Components in a Cohort of Thymic Epithelial Tumors
Authors: Palamaris Kostas , Levidou Georgia , Kordali Katerina , Masaoutis Christos , Rontogianni Dimitra , Theocharis Stamatios
Published: July 2023

Given the pivotal role of the Hippo pathway in different facets of tumorigenesis, which has been vigorously established in multiple heterogenous malignancies, we attempted to evaluate its potential utility as a prognostic–predictive biomarker in thymic epithelial tumors (TETs). For this purpose, we performed a comprehensive immunohistochemical analysis of four Hippo cascade components (YAP, TAZ, TEAD4 and LATS1) in a sizeable cohort of TETs and attempted to identify possible correlations of their H-score with various clinicopathological parameters. TAZ and TEAD4 displayed both cytoplasmic and nuclear immunoreactivity in almost equal frequency, with their cytoplasmic H-score being strongly associated with more aggressive high-grade tumors (type B3, thymic carcinoma) and more advanced pathological stages. On the other hand, a primarily nuclear staining pattern was encountered in both YAP and LATS1, with the YAP nuclear H-score being higher in more indolent (type A) and earlier stage tumors. Interestingly, none of the four examined factors displayed any statistically significant correlation with patient overall (OS) or disease-free survival (DFS). In summary, our results provide some initial insight into the expression profile of these core Hippo pathway components in thymic neoplasms and point towards some clear associations with tumor characteristics, which are of paramount translational-clinical research with profound implications in therapeutic targeting of this pathway in the context of precision medicine.
Role of Diacylglycerol Kinases in Acute Myeloid Leukemia
Authors: Gravina Teresa , Boggio Chiara Maria Teresa , Gorla Elisa , Racca Luisa , Polidoro Silvia , Centonze Sara , Ferrante Daniela , Lunghi Monia , Graziani Andrea , Corà Davide , Baldanzi Gianluca
Published: July 2023

Diacylglycerol kinases (DGKs) play dual roles in cell transformation and immunosurveillance. According to cancer expression databases, acute myeloid leukemia (AML) exhibits significant overexpression of multiple DGK isoforms, including DGKA, DGKD and DGKG, without a precise correlation with specific AML subtypes. In the TGCA database, high DGKA expression negatively correlates with survival, while high DGKG expression is associated with a more favorable prognosis. DGKA and DGKG also feature different patterns of co-expressed genes. Conversely, the BeatAML and TARGET databases show that high DGKH expression is correlated with shorter survival. To assess the suitability of DGKs as therapeutic targets, we treated HL-60 and HEL cells with DGK inhibitors and compared cell growth and survival with those of untransformed lymphocytes. We observed a specific sensitivity to R59022 and R59949, two poorly selective inhibitors, which promoted cytotoxicity and cell accumulation in the S phase in both cell lines. Conversely, the DGKA-specific inhibitors CU-3 and AMB639752 showed poor efficacy. These findings underscore the pivotal and isoform-specific involvement of DGKs in AML, offering a promising pathway for the identification of potential therapeutic targets. Notably, the DGKA and DGKH isoforms emerge as relevant players in AML pathogenesis, albeit DGKA inhibition alone seems insufficient to impair AML cell viability.
MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation
Authors: Pellot Ortiz Karolina I. , Rechberger Julian S. , Nonnenbroich Leo F. , Daniels David J. , Sarkaria Jann N.
Published: July 2023

Inhibition of the interaction between MDM2 and p53 has emerged as a promising strategy for combating cancer, including the treatment of glioblastoma (GBM). Numerous MDM2 inhibitors have been developed and are currently undergoing rigorous testing for their potential in GBM therapy. Encouraging results from studies conducted in cell culture and animal models suggest that MDM2 inhibitors could effectively treat a specific subset of GBM patients with wild-type TP53 or functional p53. Combination therapy with clinically established treatment modalities such as radiation and chemotherapy offers the potential to achieve a more profound therapeutic response. Furthermore, an increasing array of other molecularly targeted therapies are being explored in combination with MDM2 inhibitors to increase the effects of individual treatments. While some MDM2 inhibitors have progressed to early phase clinical trials in GBM, their efficacy, alone and in combination, is yet to be confirmed. In this article, we present an overview of MDM2 inhibitors currently under preclinical and clinical investigation, with a specific focus on the drugs being assessed in ongoing clinical trials for GBM patients.
Post-Traumatic Stress Response and Appendicitis in Children—Clinical Usefulness of Selected Biomarkers
Authors: Sobczak Jarosław , Burzyńska Monika , Sikora Anna , Wysocka Anna , Karawani Jakub , Sikora Janusz P.
Published: July 2023

Acute appendicitis is an inflammatory process which is one of the most frequent global causes of surgical interventions in children. The goal of the study was to determine whether acute phase proteins, that is, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6), transforming growth factor-beta1 (TGF-β1) and cortisol (HC) play a role in the pathomechanism of post-trauma stress response of the organism and to establish the impact of the applied surgical procedure and/or of inflammation on their concentrations. An additional purpose was to establish the clinical usefulness of the studied biomarkers in the diagnostics of appendicitis. CRP concentrations were quantified via the immunoturbidimetric method, while the levels of IL-6 and PCT were assessed using a bead-based multiplexed immunoassay system in a microplate format (Luminex xMAP technology); NGAL, TGF-β1 and cortisol concentrations were determined via the enzyme-linked immunosorbent assay (ELISA) technique. All the investigated biomarkers were assayed twice, i.e., immediately before the surgery and 12–24 h after its completion. Significant increases in CRP, IL-6 and PCT concentrations were found in all children subjected to laparoscopic surgeries (p = 0.001, p = 0.006, and p = 0.009, respectively) and open (classic) surgeries (p = 0.001, p = 0.016, and p = 0.044, respectively) compared to the initial concentrations. The patients undergoing classical surgery moreover presented with significant (p = 0.002, and p = 0.022, respectively) increases in NGAL and TGF-β1 levels after the procedures. In a group of children undergoing laparoscopic surgery, the appendicitis induced an increase in cortisol concentration, whereas in patients undergoing classical surgery the increase in the levels of this biomarker was caused by the type of performed surgical procedure. Simultaneously assaying the levels of CRP, NGAL and IL-6 (p = 0.008, p = 0.022, and p = 0.000, respectively) may prove useful in clinical practice, enabling the diagnosis of appendicitis in paediatric patients reporting to a hospital with abdominal pains, in addition to data from anamnesis and from clinical or ultrasound examination. The performed study confirms the participation of examined biomarkers in the pathomechanism of post-injury stress reaction of the organism to surgical trauma.
Structural Transitions of Papain-like Cysteine Proteases: Implications for Sensor Development
Authors: Marković Srdjan , Andrejević Natalija S. , Milošević Jelica , Polović Natalija Đ.
Published: July 2023

The significant role of papain-like cysteine proteases, including papain, cathepsin L and SARS-CoV-2 PLpro, in biomedicine and biotechnology makes them interesting model systems for sensor development. These enzymes have a free thiol group that is suitable for many sensor designs including strong binding to gold nanoparticles or low-molecular-weight inhibitors. Focusing on the importance of the preservation of native protein structure for inhibitor-binding and molecular-imprinting, which has been applied in some efficient examples of sensor development, the aim of this work was to examine the effects of the free-thiol-group’s reversible blocking on papain denaturation that is the basis of its activity loss and aggregation. To utilize biophysical methods common in protein structural transitions characterization, such as fluorimetry and high-resolution infrared spectroscopy, low-molecular-weight electrophilic thiol blocking reagent S-Methyl methanethiosulfonate (MMTS) was used in solution. MMTS binding led to a two-fold increase in 8-Anilinonaphthalene-1-sulfonic acid fluorescence, indicating increased hydrophobic residue exposure. A more in-depth analysis showed significant transitions on the secondary structure level upon MMTS binding, mostly characterized by the lowered content of α-helices and unordered structures (either for approximately one third), and the increase in aggregation-specific β-sheets (from 25 to 52%) in a dose-dependant manner. The recovery of this inhibited protein showed that reversibility of inhibition is accompanied by reversibility of protein denaturation. Nevertheless, a 100-fold molar excess of the inhibitor led to the incomplete recovery of proteolytic activity, which can be explained by irreversible denaturation. The structural stability of the C-terminal β-sheet rich domain of the papain-like cysteine protease family opens up an interesting possibility to use its foldamers as a strategy for sensor development and other multiple potential applications that rely on the great commercial value of papain-like cysteine proteases.
Comparison of Single-Stranded DNA Probes Conjugated with Magnetic Particles for Trans-Cleavage in Cas12a-Based Biosensors
Authors: Ivanov Aleksandr V. , Safenkova Irina V. , Zherdev Anatoly V. , Wan Yi , Dzantiev Boris B.
Published: July 2023

Biosensors based on endonuclease Cas12 provide high specificity in pathogen detection. Sensitive detection using Cas12-based assays can be achieved using trans-cleaved DNA probes attached to simply separated carriers, such as magnetic particles (MPs). The aim of this work was to compare polyA, polyC, and polyT single-stranded (ss) DNA with different lengths (from 10 to 145 nt) as trans-target probes were immobilized on streptavidin-covered MPs. Each ssDNA probe was labeled using fluorescein (5′) and biotin (3′). To compare the probes, we used guide RNAs that were programmed for the recognition of two bacterial pathogens: Dickeya solani (causing blackleg and soft rot) and Erwinia amylovora (causing fire blight). The Cas12 was activated by targeting double-stranded DNA fragments of D. solani or E. amylovora and cleaved the MP–ssDNA conjugates. The considered probes demonstrated basically different dependencies in terms of cleavage efficiency. PolyC was the most effective probe when compared to polyA or polyT probes of the same length. The minimal acceptable length for the cleavage follows the row: polyC < polyT < polyA. The efficiencies of polyC and polyT probes with optimal length were proven for the DNA targets’ detection of D. solani and E. amylovora. The regularities found can be used in Cas12a-based detection of viruses, bacteria, and other DNA/RNA-containing analytes.
A Novel Salivary Sensor with Integrated Au Electrodes and Conductivity Meters for Screening of Diabetes
Authors: Lin Chen-Wei , Tsai Yuan-Hsiung , Peng Yun-Shing , Yang Jen-Tsung , Lu Yen-Pei , Chen Mei-Yen , Tung Chun-Wu
Published: July 2023

The rise in diabetes cases is a growing concern due to the aging of populations. This not only places a strain on healthcare systems but also creates serious public health problems. Traditional blood tests are currently used to check blood sugar levels, but they are invasive and can discourage patients from regularly monitoring their levels. We recently developed nano-sensing probes that integrate Au microelectrodes and conductivity meters, requiring only 50 μL of saliva for measurement. The usage of the co-planar design of coating-free Au electrodes makes the measurement more stable, precise, and easier. This study found a positive correlation between the participant’s fasting blood sugar levels and salivary conductivity. We observed a diabetes prevalence of 11.6% among 395 adults under 65 years in this study, using the glycated hemoglobin > 6.5% definition. This study found significantly higher salivary conductivity in the diabetes group, and also a clear trend of increasing diabetes as conductivity levels rose. The prediction model, using salivary conductivity, age, and body mass index, performed well in diagnosing diabetes, with a ROC curve area of 0.75. The study participants were further divided into low and high groups based on salivary conductivity using the Youden index with a cutoff value of 5.987 ms/cm. Individuals with higher salivary conductivity had a 3.82 times greater risk of diabetes than those with lower levels, as determined by the odds ratio calculation. In conclusion, this portable sensing device for salivary conductivity has the potential to be a screening tool for detecting diabetes.
Microbiome–Gut–Mucosal–Immune–Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of the Gut Microbiome in ASD Aetiology
Authors: De Sales-Millán Amapola , Aguirre-Garrido José Félix , González-Cervantes Rina María , Velázquez-Aragón José Antonio
Published: July 2023

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome–gut–brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function and microbiota metabolites in ASD. However, a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity and the microbiome–gut–brain axis in the development of autistic symptoms severity and a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via the microbiome–gut–brain axis in a feedback circuit.
Predictors of Romanian Psychology Students’ Intention to Successfully Complete Their Courses—A Process-Based Psychology Theory Approach
Authors: Cădariu Ioana-Eva , Rad Dana
Published: July 2023

Student retention is a frequently researched issue due to the incidence of student dropout and its significance to learning outcomes. However, there are research gaps that need to be addressed in understanding the factors influencing student dropout in the context of higher education in Romania. This cross-sectional investigation aims to fill these gaps by examining the relationships between satisfaction with the specialization, self-regulation of learning behavior, students’ perceived stress, perceived acceptance from family and friends, and the intention to complete studies. The study utilizes various statistical analysis techniques, including mediation analysis and correlation analysis, to analyze the collected data. An online questionnaire was administered to non-randomized students majoring in Psychology, and a total of 144 valid and consented responses were obtained. The results reveal significant influences of satisfaction with the specialization, self-regulated learning, and students’ perceived stress on the intention to successfully complete courses. Furthermore, academic self-efficacy was found to fully mediate the relationship between satisfaction with the specialization and academic adjustment. These findings contribute to a better understanding of the student dropout process in the Romanian higher education system. By identifying the factors associated with student retention, this study provides insights that can inform the development of interventions aimed at improving students’ retention and overall learning outcomes.
Economic Evaluation of Small Public Office Buildings with Class 1 of Zero Energy Building (ZEB) in Korea by Reflecting Life Cycle Assessment (LCA)
Authors: Lee Duhwan , Kim Jaemoon , Kim Young Il
Published: July 2023

This study summarizes the technology level and economic feasibility of two small 500 m2 public office buildings that achieved a first-class Zero Energy Buildings (ZEB) certification for the first time in Korea. In addition, a Life Cycle Assessment (LCA) reflecting the ZEB performance in the operation stage was analyzed, and the LCA factors considering the characteristics of small buildings were reviewed. Moreover, an economic analysis was performed through a Net Present Value (NPV) by reflecting the ZEB and LCA, and the results showed little economic feasibility. However, adding the environmental costs calculated through the LCA to the existing energy-saving costs could offset an additional 11.6–11.7%. Therefore, including the environmental impact and cost through these LCA evaluation techniques could be a positive step toward increasing the effectiveness of ZEB applications. This study is significant in that it conducted a comprehensive analysis through ZEB and LCA in terms of carbon reduction for small buildings that achieved a first-class ZEB certification, but it is limited to only two cases.
WDR82-Mediated H3K4me3 Is Associated with Tumor Proliferation and Therapeutic Efficacy in Pediatric High-Grade Gliomas
Authors: Wadhwani Nitin , Nayak Sonali , Wang Yufen , Hashizume Rintaro , Jie Chunfa , Mania-Farnell Barbara , James Charles David , Xi Guifa , Tomita Tadanori
Published: July 2023

Pediatric high-grade gliomas (pHGGs) are common malignant brain tumors without effective treatment and poor patient survival. Abnormal posttranslational modification at the histone H3 tail plays critical roles in tumor cell malignancy. We have previously shown that the trimethylation of lysine 4 at histone H3 (H3K4me3) plays a significant role in pediatric ependymoma malignancy and is associated with tumor therapeutic sensitivity. Here, we show that H3K4me3 and its methyltransferase WDR82 are elevated in pHGGs. A reduction in H3K4me3 by downregulating WDR82 decreases H3K4me3 promoter occupancy and the expression of genes associated with stem cell features, cell proliferation, the cell cycle, and DNA damage repair. A reduction in WDR82-mediated H3K4me3 increases the response of pediatric glioma cells to chemotherapy. These findings suggest that WDR82-mediated H3K4me3 is an important determinant of pediatric glioma malignancy and therapeutic response. This highlights the need for a more thorough understanding of the potential of WDR82 as an epigenetic target to increase therapeutic efficacy and improve the prognosis for children with malignant gliomas.
Leveraging Gene Redundancy to Find New Histone Drivers in Cancer
Authors: Ostroverkhova Daria , Espiritu Daniel , Aristizabal Maria J. , Panchenko Anna R.
Published: July 2023

Histones play a critical role in chromatin function but are susceptible to mutagenesis. In fact, numerous mutations have been observed in several cancer types, and a few of them have been associated with carcinogenesis. Histones are peculiar, as they are encoded by a large number of genes, and the majority of them are clustered in three regions of the human genome. In addition, their replication and expression are tightly regulated in a cell. Understanding the etiology of cancer mutations in histone genes is impeded by their functional and sequence redundancy, their unusual genomic organization, and the necessity to be rapidly produced during cell division. Here, we collected a large data set of histone gene mutations in cancer and used it to investigate their distribution over 96 human histone genes and 68 different cancer types. This analysis allowed us to delineate the factors influencing the probability of mutation accumulation in histone genes and to detect new histone gene drivers. Although no significant difference in observed mutation rates between different histone types was detected for the majority of cancer types, several cancers demonstrated an excess or depletion of mutations in histone genes. As a consequence, we identified seven new histone genes as potential cancer-specific drivers. Interestingly, mutations were found to be distributed unevenly in several histone genes encoding the same protein, pointing to different factors at play, which are specific to histone function and genomic organization. Our study also elucidated mutational processes operating in genomic regions harboring histone genes, highlighting POLE as a factor of potential interest.
Sorafenib in Molecularly Selected Cancer Patients: Final Analysis of the MOST-Plus Sorafenib Cohort
Authors: Trédan Olivier , Toulmonde Maud , Le Tourneau Christophe , Montane Laure , Italiano Antoine , Ray-Coquard Isabelle , De La Fouchardière Christelle , Bertucci François , Gonçalves Anthony , Gomez-Roca Carlos , You Benoit , Attignon Valéry , Boyault Sandrine , Cassier Philippe A. , Dufresne Armelle , Tabone-Eglinger Séverine , Viari Alain , Sohier Emilie , Kamal Maud , Garin Gwenaël , Blay Jean-Yves , Pérol David
Published: July 2023

Background: MOST-plus is a multicenter, randomized, open-label, adaptive Phase II trial evaluating the clinical benefit of targeted treatments matched to molecular alteration in advanced/metastatic solid tumors. Sorafenib was tested on patients with tumors harboring sorafenib-targeted genes. Methods: The MOST-plus trial used a randomized discontinuation design. After 12 weeks of sorafenib (400 mg, po BID), patients with progressive disease discontinued study, patients with objective response were proposed to continue sorafenib, whereas patients with stable disease (SD) were randomly assigned (1:1) to the maintenance or interruption of treatment. The primary endpoint was RECIST version 1.1 progression-free rate at 16 weeks after randomization (PFR-16w). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Statistical analyses used a sequential Bayesian approach with interim efficacy analyses. The enrolment could be stopped in the case of a 95% probability for the estimated PFR-16w to be higher in the maintenance than in the interruption arm (NCT02029001). Results: 151 patients were included, of whom 35 had SD at 12 weeks of Sorafenib. For the 35 patients with SD on sorafenib, the PFR-16w was 65% [95% credibility interval 43.4–83.7] in the continuation arm and 25% [7.8–48.1] in the interruption arm. Median PFS and OS were improved in the maintenance versus the interruption arm (mPFS: 5.6 [95%CI 1.97–6.77] months versus 2.0 [95%CI 1.61–3.91] months (p = 0.0231) and mOS: 14.3 [95%CI 8.9–23.8] versus 8.0 months [95%CI 3.5–15.2] (p = 0.0857)). Conclusion: Sorafenib showed activity in progressive patients with solid tumors harboring somatic genomic alterations in sorafenib-targeted genes. Continuing sorafenib when SD is achieved improves PFR compared to interruption.
A Comparison of Total Thoracoscopic and Robotic Surgery for Lung Cancer Lymphadenectomy
Authors: Ureña Anna , Moreno Camilo , Macia Ivan , Rivas Francisco , Déniz Carlos , Muñoz Anna , Serratosa Ines , García Marta , Masuet-Aumatell Cristina , Escobar Ignacio , Ramos Ricard
Published: July 2023

Background: Robotic-assisted thoracic surgery (RATS) is used increasingly frequently in major lung resection for early stage non-small-cell lung cancer (NSCLC) but has not yet been fully evaluated. The aim of this study was to compare the surgical outcomes of lymph node dissection (LND) performed via RATS with those from totally thoracoscopic (TT) four-port videothoracoscopy. Methods: Clinical and pathological data were collected retrospectively from patients with clinical stage N0 NSCLC who underwent pulmonary resection in the form of lobectomy or segmental resection between June 2010 and November 2022. The assessment criteria were number of mediastinal lymph nodes and number of mediastinal stations dissected via the RATS approach compared with the four-port TT approach. Results: A total of 246 pulmonary resections with LND for clinical stages I–II NSCLC were performed: 85 via TT and 161 via RATS. The clinical characteristics of the patients were similar in both groups. The number of mediastinal nodes dissected and mediastinal stations dissected was significantly higher in the RATS group (TT: mean ± SD, 10.72 ± 3.7; RATS, 14.74 ± 6.3 [p < 0.001]), except in the inferior mediastinal stations. There was no difference in terms of postoperative complications. Conclusions: In patients with early stage NSCLC undergoing major lung resection, the quality of hilomediastinal LND performed using RATS was superior to that performed using TT.
Prophylactic A-Blockers for Radiotherapy-Induced Lower Urinary Tract Symptoms in Men with Prostate Cancer: A Phase III Randomized Trial
Authors: Niazi Tamim , Kaldany Edmond , Tisseverasinghe Steven , Malagón Talía , Bahoric Boris , McPherson Victor , Rompre-Brodeur Alexis , Anidjar Maurice
Published: July 2023

Purpose: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). Methods: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. Results: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. Conclusion: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity.