bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Androstenedione Concentration Can Discriminate Frail versus Non-Frail Men with Prostate Cancer under Androgen Deprivation Therapy
Authors: Mafla-España Mayra Alejandra , Torregrosa María Dolores , Beamud-Cortés Manel , Bermell-Marco Lorena , Rubio-Briones José , Cauli Omar
Published: November 2023

Background: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). Methods: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. Results: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30–16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55–0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. Conclusions: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.
Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery
Authors: Garcia-Puente Luis M. , Fraile-Martinez Oscar , García-Montero Cielo , Bujan Julia , De León-Luis Juan A. , Bravo Coral , Rodríguez-Benitez Patrocinio , Pintado Pilar , Ruiz-Labarta Francisco Javier , Álvarez-Mon Melchor , García-Honduvilla Natalio , Cancelo María J. , Saez Miguel A. , Ortega Miguel A.
Published: November 2023

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.
Chemical Trends in Sample Preparation for Nucleic Acid Amplification Testing (NAAT): A Review
Authors: Lee Soo Min , Balakrishnan Hari Kalathil , Doeven Egan H. , Yuan Dan , Guijt Rosanne M.
Published: November 2023

Nucleic acid amplification testing facilitates the detection of disease through specific genomic sequences and is attractive for point-of-need testing (PONT); in particular, the early detection of microorganisms can alert early response systems to protect the public and ecosystems from widespread outbreaks of biological threats, including infectious diseases. Prior to nucleic acid amplification and detection, extensive sample preparation techniques are required to free nucleic acids and extract them from the sample matrix. Sample preparation is critical to maximize the sensitivity and reliability of testing. As the enzymatic amplification reactions can be sensitive to inhibitors from the sample, as well as from chemicals used for lysis and extraction, avoiding inhibition is a significant challenge, particularly when minimising liquid handling steps is also desirable for the translation of the assay to a portable format for PONT. The reagents used in sample preparation for nucleic acid testing, covering lysis and NA extraction (binding, washing, and elution), are reviewed with a focus on their suitability for use in PONT.
Biosensors Based on Stanniocalcin-1 Protein Antibodies Thin Films for Prostate Cancer Diagnosis
Authors: Ferreira Renato , Ribeiro Paulo A. , Canário Adelino V. M. , Raposo Maria
Published: November 2023

Prostate cancer is one of the most prevalent tumors in men, accounting for about 7.3% of cancer deaths. Although there are several strategies for diagnosing prostate cancer, these are only accurate when the tumor is already at a very advanced stage, so early diagnosis is essential. Stanniocalcin 1 (STC1) is a secreted glycoprotein, which has been suggested as a tumor marker as its increased expression is associated with the development and/or progression of different types of malignant tumors. In this work, an electronic tongue (ET) prototype, based on a set of four sensors prepared from thin films that included STC1 antibodies for detecting prostate cancer, was developed. In the preparation of the thin films, polyelectrolytes of polyallylamine hydrochloride, polystyrene sulfonate of sodium and polyethyleneimine, and the biomolecules chitosan, protein A, and STC1 antibody were used. These films were deposited on quartz lamellae and on solid supports using layer-on-layer and self-assembly techniques. The deposition of the films was analyzed by ultraviolet-visible spectroscopy, and the detection of STC1 in aqueous solutions of PBS was analyzed by impedance spectroscopy. The impedance data were statistically analyzed using principal component analysis. The ETs formed by the four sensors and the three best sensors could detect the antigen at concentrations in the range from 5 × 10−11 to 5 × 10−4 M. They showed a linear dependence with the logarithm of the antigen concentration and a sensitivity of 5371 ± 820 and 4863 ± 634 per decade of concentration, respectively. Finally, the results allow us to conclude that this prototype can advance to the calibration phase with patient samples.
Noncontact Cardiac Activity Detection Based on Single-Channel ISM Band FMCW Radar
Authors: Qu Kui , Wei Lei , Zhang Rongfu
Published: November 2023

The heart is an important organ that maintains human life activities, and its movement reflects its health status. Utilizing electromagnetic waves as a sensing tool, radar sensors enable noncontact measurement of cardiac motion, offering advantages over conventional contact-based methods in terms of comfort, hygiene, and efficiency. In this study, the high-precision displacement detection algorithm of radar is applied to measure cardiac motion. Experimental is conducted using a single out-channel frequency modulated continuous wave (FMCW) radar operating in the ISM frequency band with a center frequency of 24 GHz and a bandwidth of 150 MHz. Since the detection signal is influenced by both respiratory and heartbeat movements, it is necessary to eliminate the respiratory signal from the measurement signal. Firstly, the harmonic composition of the respiratory signal is analyzed, and a method is proposed to calculate the parameters of the respiratory waveform by comparing the respiratory waveform coverage area with the area of the circumscribed rectangle. This allows for determining the number of respiratory harmonics, assisting in determining whether respiratory harmonics overlap with the frequency range of the heartbeat signal. Subsequently, a more accurate cardiac motion waveform is extracted. A reference basis is provided for extracting cardiac health information from radar measurement waveforms by analyzing the corresponding relationship between certain extreme points of the waveform and characteristic positions of the electrocardiogram (ECG) signal. This is achieved by eliminating the fundamental frequency component of the heartbeat waveform to emphasize other spectral components present in the heartbeat signal and comparing the heartbeat waveform, the heartbeat waveform with the fundamental frequency removed, and the heartbeat velocity waveform with synchronized ECG signals.
The Effects of Emotion, Spokesperson Type, and Benefit Appeals on Persuasion in Health Advertisements: Evidence from Macao
Authors: Jiang Ling , Liu Huihui , Jiang Nan
Published: November 2023

Enhancing public awareness for epidemic prevention is crucial for safeguarding public health. This experimental study investigated the effectiveness of a combined approach involving three persuasive elements in public health advertising. Specifically, the study examined the interplay between emotional appeals (fear messages versus efficacy messages) and spokesperson type on the public’s response to health announcements. The results demonstrated that fear messages were more persuasive when conveyed by real human spokespersons (versus animated spokespersons), whereas efficacy messages were more acceptable when conveyed by animated spokespersons (versus real humans). Furthermore, the study revealed that the impact of emotional appeals and spokesperson type is moderated by benefit appeals (self-benefit or other-benefit). The joint effects of these persuasive variables on individuals’ intention to adopt preventive measures indicated that the interactions significantly differed across the two types of benefit appeal. Taken together, the findings represent a pioneering contribution to the field of health communication by comparing the persuasive effects of different combinations of emotional appeals, spokesperson types, and benefit appeals on public behavior. These findings offer practical guidance for public communicators to design more appropriate health advertisements based on the results of this study, thereby enhancing public acceptance of disease prevention measures.
Reciprocal Associations among Social–Emotional Competence, Interpersonal Relationships and Academic Achievements in Primary School
Authors: Yang Jiaqi , Deng Yuze , Wang Yehui
Published: November 2023

The study aimed to examine the reciprocal associations among social–emotional competence (SEC), interpersonal relationships (including teacher–student relationships and peer relationships) and academic achievements in reading, mathematics and science of primary school students. The Chinese versions of the Delaware Social and Emotional Competency Scale, Teacher–student Relationship Scale, Peer-nomination method and Academic Achievement Tests were used to measure students’ SEC, teacher–student relationships, peer relationships (including social preference (SP) and social impact (SI)) and academic achievements, respectively. In total, 3995 fourth-grade students participated in the first survey, and 2789 of them were tracked in the follow-up survey two years later. Structural equation modelling was employed to investigate the cross-lagged relationships among the variables across time. The results showed the reciprocal associations between SEC with academic achievements and teacher–student relationships, as well as between academic achievements with SP and teacher–student relationships. Moreover, variations in these reciprocal associations were observed across the subjects of reading, mathematics and science. In summary, this study offers new insights for enhancing students’ SEC, interpersonal relationships and academic achievements, and implications for future subject-specific education can be derived by considering the complex interplay in the subjects of reading, mathematics and science.
Analysis of Psychological Well-Being from a Compositional Data Analysis Perspective: A New Approach
Authors: Cortés-Rodríguez María , Galindo-Villardón Purificación , Sánchez-Barba Mercedes , Jarauta-Bragulat Eusebi , Urchaga-Litago José David
Published: November 2023

Well-being is a widely studied construct in psychology. In 1989, Carol Ryff proposed the “Scale of Psychological Well-Being (SPWB)”, which has been validated in multiple languages. The instrument assesses six dimensions of psychological well-being: Self-acceptance, Positive Relationships with Others, Autonomy, Environmental Mastery, Purpose in Life, and Personal Growth. In this article, we propose to enrich the traditional approach of directly interpreting the raw scores in each dimension by incorporating Compositional Data Analysis. This new approach aims to identify “what proportion” of each dimension constitutes well-being, which will allow us to analyze the interactions between the different dimensions of well-being and balance among them. To achieve this, we introduce two position ratios (PR1 and PR2) and a general adjustment indicator called the General Indicator of Subjective Psychological Well-Being (GISPW), which characterizes individuals in a compositional manner, providing a fresh perspective in the interpretation of psychological test results, specifically those related to PWB. The proposal is illustrated with three cases taken from a study involving 628 university students who completed the psychological well-being scale questionnaire. The results show that the GISPW, PR1, and PR2 obtained offer relevant information about the overall balance of each case in the different dimensions.
Post-Cracking Shear Stiffness Model of Reinforced Concrete Beams
Authors: Zheng Kaiqi , Ni Siwen , Zhang Yaohui , Gu Junxuan , Gao Mingming , Wei Yang
Published: November 2023

Macro diagonal cracks can significantly reduce the stiffness of slender reinforced concrete (RC) beams, which results in excessive deflection compared with limitations from design specifications. To evaluate the post-cracking stiffness of slender RC beams with diagonal cracks, a shear degradation model that considers shear deformation is proposed. Based on the variable angle truss model, this study deduced the strut angle formula based on the minimum energy principle. Then, the relationship between the stirrup yielding shear stiffness and elastic shear stiffness was modeled. Finally, the calculation procedure was developed by quantifying the stiffness degradation tendency. The comparison between the experimental results of deflection and the proposed analytical method showed good agreement. Additionally, the proposed method can capture the full-range features of shear strain curves.
Finite Element Analysis and Parametric Study of Panel Zones in H-Shaped Steel Beam–Column Joints
Authors: Li Wei , Fan Hai-Tao , Ye Heng , Lin Xu-Chuan , Chen Lian-Meng
Published: November 2023

This paper investigates the mechanical properties of a traditional welded rigid joint with a weakened panel zone under seismic load. The created finite element model is calibrated by the high-strength steel joint test, carried out by the team in the early stage, and the effectiveness of the finite element method was verified. The finite element software ABAQUS is used to investigate the influence of different joint web thicknesses on the mechanical properties of middle column joints under a low-cyclic-loading test. Supported by a validated numerical model, the ductility, energy dissipation, and other properties of different thicknesses of panel zone column webs are carefully analyzed. The results indicate that the thickness of the web plate in the panel zone significantly affects the location of the joint plastic hinge. The ultimate loading capacity of the joints increased significantly with an increase in the thickness of the webs in the panel zones. Compared with the joint with a weakened panel zone, the hysteresis curve of the strengthened joint is fuller; meanwhile, it cannot alleviate the stress concentration at the weld holes of the web. When the thickness of the joint domain web is too weak, excessive deformation in the joint domain will lead to a decrease in the bearing capacity of the joint, causing damage. The stiffness degradation coefficient of the web-thickened specimen was found to be dominated and controlled by the stiffness of the beam; however, with an increase in the thickness of the web, the stiffness degradation coefficient remained basically unchanged. Finally, a recommendation for weakened beam–column interior joints based on the steel frame panel zone is made, which will lay a foundation for the simulation and analysis of the seismic performance of this structure.
Assessing Distributional and Perceived Equity of Urban Green Spaces in Qingdao’s Historic Urban Area
Authors: Jiang Naibin , Li Xinyu , Peng Zhen , Ban Qichao , Feng Yuting
Published: November 2023

Urban green spaces (UGSs) satisfy citizens’ physical and psychological demands and are considered an integral part of sustainable urban development. However, the distribution of UGS is often uneven, especially in historic urban areas with high building density and limited facilities, thus leading to issues of green inequity. This study examines two dimensions of green equity in Qingdao’s historic urban area, distributional equity and perceived equity, based on a fine-grained division of units and districts. Distributional equity is analyzed using the Gaussian two-step floating catchment area (G2SFCA) method and Gini coefficient to accurately calculate the equity in distribution and accessibility of UGSs. The perceived equity is assessed through the green view index (GVI) and location quotient of the streets, which represents citizens’ visual perception of green quality. Based on these analyses, a dual-perspective evaluation model of green equity is conducted, and the results show a significant imbalance of greenery supply and population demand in the historical urban area of Qingdao. This disequilibrium in green spaces leads to 62.20% of people living with low green equity, while only 8.12% experience high green equity. To maximize social justice, priority should be given to improving the 15 districts with low green equity; doing so could effectively reduce green inequity within historic urban areas where facilities and resources are relatively scarce, thereby improving the efficiency of urban renewal efforts.
A Simplified Limit-State Design and Verification for Prestressed Concrete Cylinder Pipes under Internal Water Pressure
Authors: Shang Pengran , Qu Fulai , Wang Jun , Geng Yunsheng , Yan Tianqiong , Zhao Shunbo
Published: November 2023

Ignoring the effect of a concrete core on bearing performance, the current design of prestressed concrete cylinder pipes (PCCPs) under internal water pressure only focuses on the fracture of prestressed steel wire, while the complexity of the AWWA C304 design method leads to a strong dependence on software that cannot be sufficiently mastered by the designers. In view of these issues, a simplified limit-state design process was induced to eliminate a large number of iterative operations and was verified by a three-dimensional finite element model (FEM) with a prototype test of PCCPs under internal water pressure. Meanwhile, the bearing performance of PCCPs was investigated using the parametric simulations of the FEM. The results showed that the cross-sectional area of the prestressed steel wire is higher by about 10% than that designed using the AWWA C304 method. The FEM provides a complete evolution process of the mechanical response of the structural constituents and simulates the strain mutation phenomenon of the prototype test well. The internal water pressure of the PCCPs designed using the simplified limit-state design process has enough safety to reach 4.7 times the working pressure at serviceability and 5.5 times the pressure at the ultimate limit state. A burst in the PCCPs took place under an internal pressure greater than 6.75 times the working pressure. The result of the FEM shows that an increase in the tensile strength of the concrete core is of great significance for improving the bearing performance of the PCCPs.
Seeking the Optimisation of Public Infrastructure Procurement with NEC4 ECC: A Peruvian Case Study
Authors: Yabar-Ardiles Oscar , Sanchez-Carigga Carlos , Espinoza Vigil Alain Jorge , Guillén Málaga Milagros Socorro , Milón Zevallos Andreé Alexis
Published: November 2023

The modern civil engineering and construction sector requires collaborative work environments, learning and trust among all parties involved, qualities that are absent in the Peruvian reality. This study, which is based on an extensive literature review, investigates this challenge. The study reflects upon (i) the current situation of public works procurement in Peru and (ii) the New Engineering Contract (NEC), which has recently been implemented in Peruvian Special Public Infrastructure Projects. Comparisons are presented between the characteristics, documentation and roles of these two systems, with the purpose of understanding and representing the advantages, disadvantages and possibilities of integrating the good contractual management practices of the NEC4 Engineering and Construction Contract into the traditional Peruvian State Contracting Law (Ley de Contrataciones del Estado: LCE). The research is validated through the case study of a high-impact road infrastructure project in the city of Arequipa, Peru, which revealed five main deficiencies from Peruvian procurement processes which hinder good contractual management and, also, facilitated an initial assessment of the challenges and improvement opportunities in public infrastructure procurement. Thus, a contribution is made to closing the knowledge gap regarding the implementation of the NEC4 ECC in public sector works.
Investigation of Mechanical and Physical Features of Cementitious Jet Grout Applications for Various Soil Types
Authors: Cinar Muhammet
Published: November 2023

The cementitious jet grout method (CJG) is one of the most preferred methods for the ground reinforcement of building foundations. As a result of the soil improvement made with the CJG, it was observed that there was a decrease in settlement, permeability, and liquefaction potential and an increase in the bearing capacity. In this study, columns with different grouting pressures (400, 450, and 500 bar) and water/cement ratios of 0.75, 1.00, and 1.25 were produced on several soil types (sand, clay, and alluvial soil) that have high liquefaction, settlement potential, and low bearing capacity. CJG columns were kept for 28 days after completion and then removed from the soil, and diameter measurements were made and significant differences were observed according to pressure and w/c ratios. Three samples were taken in CJG columns extracted from the ground. Laboratory tests were conducted to determine the physical (water absorption rate, density, and porosity) and mechanical (UCS and UPV) properties of CJG column samples. The highlighting of this paper is to build full-scale CJG columns in sandy soil, clay soil, and alluvial soil, increase the geotechnical engineering properties, and investigate the strength development, and diameter under different w/c ratios and different injection pressures. The strength of CJG columns in sandy soils was found between 36 and 15 MPa, in clay soils between 15 and 4 MPa and in alluvial soils between 32 and 15 MPa. Moreover, it was observed that there was a significant increase in the diameters with the increase in the injection pressure and a decrease in the compressive strengths. When the CJG column diameters were compared with constant injection pressure and increasing w/c ratios, the maximum increase was found to be 13% for sandy soils, 10% for clayey soils, and 14% for alluvial soils. The column diameters were 37% larger for sandy soils than clayey soils and 26% larger than alluvial soils at the same w/c ratio and constant injection pressure. In conclusion, since the results found in this study were made on a real scale in the field and for three different soil conditions, the results can be used directly in future engineering applications.
Blast Resistance in Sandwich Structures Based on TPMS
Authors: He Li , Li Tengfei , Zhong Dongwang , Tao Haohao , Peng Yuesen , Chen Shasha
Published: November 2023

This study analyzes the blast resistance in triple-period minimal surface (TPMS) sandwich panel structures with a cellular structure. The explosion test of the TPMS sandwich panel was carried out, and experimental data verified the effectiveness of the finite element model. Four TPMS configurations, Diamond, Gyroid, IWP, and Primitive, were selected as the core of the sandwich panel to determine the dynamic response process of the TPMS sandwich panel under the action of a blast load. The effects of the thickness of the core material and the explosive charge on the blast resistance in the TPMS sandwich panel were investigated. The results show that the increase in core thickness reduces the blast energy absorption efficiency of the sandwich panel, and the energy resistance in the Diamond configuration sandwich panel is stronger than the other three configurations under the same blast load; the increase in explosive charge significantly increases the displacement of the sandwich panel, and the Gyroid configuration shows better energy absorption effect; different TPMS configurations and panel thickness have a significant effect on the deformation and energy absorption of the sandwich panel under the blast load. The results of this study can promote the application of TPMS sandwich structures in blast-resistant structures.
Recent Progress in Enhanced Cancer Diagnosis, Prognosis, and Monitoring Using a Combined Analysis of the Number of Circulating Tumor Cells (CTCs) and Other Clinical Parameters
Authors: Nguyen Thi Ngoc Anh , Huang Po-Shuan , Chu Po-Yu , Hsieh Chia-Hsun , Wu Min-Hsien
Published: November 2023

Analysis of circulating tumor cells (CTCs) holds promise to diagnose cancer or monitor its development. Among the methods, counting CTC numbers in blood samples could be the simplest way to implement it. Nevertheless, its clinical utility has not yet been fully accepted. The reasons could be due to the rarity and heterogeneity of CTCs in blood samples that could lead to misleading results from assays only based on single CTC counts. To address this issue, a feasible direction is to combine the CTC counts with other clinical data for analysis. Recent studies have demonstrated the use of this new strategy for early detection and prognosis evaluation of cancers, or even for the distinguishment of cancers with different stages. Overall, this approach could pave a new path to improve the technical problems in the clinical applications of CTC counting techniques. In this review, the information relevant to CTCs, including their characteristics, clinical use of CTC counting, and technologies for CTC enrichment, were first introduced. This was followed by discussing the challenges and new perspectives of CTC counting techniques for clinical applications. Finally, the advantages and the recent progress in combining CTC counts with other clinical parameters for clinical applications have been discussed.
ARID1A Deficiency Regulates Anti-Tumor Immune Response in Esophageal Adenocarcinoma
Authors: Zhang Le , Zheng Yueyuan , Chien Wenwen , Ziman Benjamin , Billet Sandrine , Koeffler H. Phillip , Lin De-Chen , Bhowmick Neil A.
Published: November 2023

ARID1A, a member of the chromatin remodeling SWI/SNF complex, is frequently lost in many cancer types, including esophageal adenocarcinoma (EAC). Here, we study the impact of ARID1A deficiency on the anti-tumor immune response in EAC. We find that EAC tumors with ARID1A mutations are associated with enhanced tumor-infiltrating CD8+ T cell levels. ARID1A-deficient EAC cells exhibit heightened IFN response signaling and promote CD8+ T cell recruitment and cytolytic activity. Moreover, we demonstrate that ARID1A regulates fatty acid metabolism genes in EAC, showing that fatty acid metabolism could also regulate CD8+ T cell recruitment and CD8+ T cell cytolytic activity in EAC cells. These results suggest that ARID1A deficiency shapes both tumor immunity and lipid metabolism in EAC, with significant implications for immune checkpoint blockade therapy in EAC.
Cytokine Profile in Lung Cancer Patients: Anti-Tumor and Oncogenic Cytokines
Authors: Essogmo Freddy Elad , Zhilenkova Angelina V. , Tchawe Yvan Sinclair Ngaha , Owoicho Abah Moses , Rusanov Alexander S. , Boroda Alexander , Pirogova Yuliya N. , Sangadzhieva Zaiana D. , Sanikovich Varvara D. , Bagmet Nikolay N. , Sekacheva Marina I.
Published: November 2023

Lung cancer is currently the second leading cause of cancer death worldwide. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment (TMJ) or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body’s response to inflammation and infection. Cytokines are important for immunity in lung cancer. They promote tumor growth (oncogenic cytokines) or inhibit tumor growth (anti-tumour cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system to stop the growth or kill cancer cells. Interleukins and interferons are the two types of cytokines used to treat cancer. This article begins by addressing the role of the TMJ and its components in lung cancer. This review also highlights the functions of various cytokines such as interleukins (IL), transforming growth factor (TGF), and tumor necrosis factor (TNF).
Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches
Authors: Tojjari Alireza , Saeed Anwaar , Sadeghipour Arezoo , Kurzrock Razelle , Cavalcante Ludimila
Published: November 2023

SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple human cancers and is considered a promising therapeutic target for treating these malignancies. The PTPN11 gene and functions encode SHP2 as a critical signal transduction regulator that interacts with key signaling molecules in both the RAS/ERK and PD-1/PD-L1 pathways; SHP2 is also implicated in T-cell signaling. SHP2 may be inhibited by molecules that cause allosteric (bind to sites other than the active site and attenuate activation) or orthosteric (bind to the active site and stop activation) inhibition or via potent SHP2 degraders. These inhibitors have anti-proliferative effects in cancer cells and suppress tumor growth in preclinical models. In addition, several SHP2 inhibitors are currently in clinical trials for cancer treatment. This review aims to provide an overview of the current research on SHP2 inhibitors, including their mechanism of action, structure-activity relationships, and clinical development, focusing on immune modulation effects and novel therapeutic strategies in the immune-oncology field.
Solketal Production Using Eco-Friendly Reduced Graphene Oxide as the Catalyst
Authors: Rossa Vinicius , Vasconcelos Sancler da Costa , Díaz Gisel Chenard , Resende Josué de Almeida , Mattos João Pedro Reys , Madriaga Vinicius Gomes da Costa , Massante Fernanda Franco , Cruz Yordanka Reyes , Nachez Juan Lucas , Xing Yutao , Ponzio Eduardo Ariel , Lima Thiago de Melo
Published: November 2023

In this study, two materials based on reduced graphene oxide (rGOH or rGOE) were synthesized through the Hummers methodology and a more sustainable electrochemical method. These materials were extensively characterized and tested as catalysts in solketal production. Both rGOH and rGOE demonstrated significant catalytic activity, achieving 66.18% and 63.97% conversion rates, respectively. The catalytic activity of the synthesized materials was 30 times more efficient than the homogeneous catalyst p-Toluenesulfonic acid. Pseudo-homogeneous and heterogeneous kinetic models were employed to gain further insights into the glycerol ketalization reaction with acetone. The pseudo-homogeneous model suggested that the direct rate constant was lower than the reverse rate constant. In this sense, a reversible bimolecular reaction was proposed. The heterogeneous kinetic models revealed that in the Langmuir-Hinshelwood-Hougen-Watson mechanism, the controlling step of the reaction was the glycerol-acetone surface reaction on the catalyst. In contrast, in the Eley-Rideal mechanism, the reaction was controlled by the adsorbed glycerol on the reaction surface reacting with the available acetone in the bulk fluid. In the reusability tests, the rGOE catalyst demonstrated superior performance over five consecutive cycles, maintaining the highest activity without needing post-reaction washing or treatment.
GC/MS Profiling, In Vitro Antidiabetic Efficacy of Origanum compactum Benth. Essential Oil and In Silico Molecular Docking of Its Major Bioactive Compounds
Authors: Assaggaf Hamza , El Hachlafi Naoufal , El fadili Mohamed , Elbouzidi Amine , Ouassou Hayat , Jeddi Mohamed , Alnasser Sulaiman Mohammed , Qasem Ahmed , Attar Ammar , AL-Farga Ammar , Alghamdi Othman A. , Mehana Elsayed Eldeeb , Mrabti Hanae Naceiri
Published: November 2023

Diabetes is a global health concern with significant implications for individuals and healthcare systems. Finding effective and safe antidiabetic agents is crucial for the management of this chronic disease. Natural products have emerged as potential alternatives to allopathic drugs, offering a vast source of bioactive compounds. In this study, we conducted an assessment of the antidiabetic potential of Origanum compactum essential oil, employing a two-pronged approach, i.e., experimental investigation and computational docking analysis. The results of gas chromatography–mass spectrometry (GC-MS) showed that thymol (54.6%), carvacrol (23.18%), and p-cymene (7.12%) were the major compounds. Experimental assessments revealed higher IC50 values (150 µg/mL for α-amylase; 120 µg/mL for α-glucosidase) of O. compactum oil, compared to the control drug acarbose. In silico analysis revealed the best binding affinity of the oil components (carvacrol and thymol) with human NADPH oxidase, while the lysosomal acid-α-glucosidase and salivary amylase also demonstrated good binding affinity towards carvacrol and thymol. Our findings highlight the translational potential of O. compactum oil-based treatment for diabetes mellitus and provide a basis for further studies on the modulation of NADPH oxidase, amylase inhibition, and α-glucosidase by antidiabetic natural products. However, further in vivo investigations are strongly required to confirm the results of in vitro antidiabetic effect of O. compactum EO.
Effect of Support on Oxidative Esterification of 2,5-Furandiformaldehyde to Dimethyl Furan-2,5-dicarboxylate
Authors: Ge Tingting , Liu Xiaorui , Tang Jie , Liu Chao , Huang Jiahui
Published: November 2023

One-step oxidative esterification of 2,5-furandiformaldehyde (DFF) derived from biomass to prepare Dimethyl Furan-2,5-dicarboxylate (FDMC) not only simplifies the catalytic process and increases the purity of the product, but also avoids the polymerization of 5-hydroxymethylfurfural (HMF) at high-temperature conditions. Gold supported on a series of acidic oxide, alkaline oxide, and hydrotalcite was prepared using colloidal deposition to explore the effect of support on the catalytic activities. The Au/Mg3Al-HT exhibited the best catalytic activity, with 97.8% selectivity of FDMC at 99.9% conversion of DFF. This catalyst is also suitable for oxidative esterification of benzaldehyde and furfural. X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and CO2 temperature programmed desorption (CO2-TPD) were performed to characterize the catalysts. The results indicated that the medium and strong basic sites in the catalysts benefited for the absorption of intermediate agents and facilitated the oxidative esterification of aldehyde groups, while neutral or acidic supports tended to produce an acetal reaction. It is worth noting that basicity on the support surface reduced the electronic state of the Au nanoparticle (Auδ−) and, thus, enhanced the catalytic selectivity of oxidative esterification. This finding demonstrated that the support plays a crucial role in oxidative esterification.
Cyano/Hydroxyl Groups Co-Functionalized g-C3N4 for Photocatalytic NO Removal: A Synergistic Strategy towards Inhibition of Toxic Intermediate NO2
Authors: Wang Hui , Xu Xiaoqian , Labidi Abdelkader , Ren Haitao , Allam Ahmed A. , Rady Ahmed , Huang Yu , Wei Shuwei , Padervand Mohsen , Ghasemi Shahnaz , Wang Chuanyi
Published: November 2023

Photocatalytic NO removal is usually accompanied by the generation of NO2, an intermediate with a higher toxicity than NO. Therefore, it is critically important to develop new photocatalysts capable of NO selective conversion. Herein, we report on the synergistic roles of cyano and hydroxyl functional groups in photocatalytic NO removal. According to the results, the NO2 production efficiencies on cyano/hydroxyl-group-modified g-C3N4 (DCN-O-R) was limited to 4.8%, which was lower than that of cyano-group-modified g-C3N4 (DCN, 38.6%) and pure g-C3N4 (CN, 50.0%). Meanwhile, the photocatalytic NO conversion efficiency over DCN-O-R was higher than that of DCN and g-C3N4. It was found that the insertion of cyano groups favorably changes the energy band of g-C3N4 towards the generation of •O2−. NO can only be oxidized to NO2 by the photogenerated holes. When NO2 is adsorbed on the surface of hydroxyl groups, it can be further oxidized to the product NO3− by •O2−. The synergistic effect of bifunctional groups regulates the conversion pathway from NO→NO2 to NO→NO2→NO3−. This work provides a strategy to abate toxic intermediates during the NO removal process, underlining the importance of surface/interface molecular engineering in regulating catalytic reaction pathways.
Sulfur and Water Resistance of Carbon-Based Catalysts for Low-Temperature Selective Catalytic Reduction of NOx: A Review
Authors: Shen Zhenghua , Ren Shan , Zhang Baoting , Bian Weixin , Xing Xiangdong , Zheng Zhaoying
Published: November 2023

Low-temperature NH3-SCR is an efficient technology for NOx removal from flue gas. The carbon-based catalyst designed by using porous carbon material with great specific surface area and interconnected pores as the support to load the active components shows excellent NH3-SCR performance and has a broad application prospect. However, overcoming the poor resistance of H2O and SO2 poisoning for carbon-based catalysts remains a great challenge. Notably, reviews on the sulfur and water resistance of carbon-based low-temperature NH3-SCR catalysts have not been previously reported to the best of our knowledge. This review introduces the reaction mechanism of the NH3-SCR process and the poisoning mechanism of SO2 and H2O to carbon-based catalysts. Strategies to improve the SO2 and H2O resistance of carbon-based catalysts in recent years are summarized through the effect of support, modification, structure control, preparation methods and reaction conditions. Perspective for the further development of carbon-based catalysts in NOx low-temperature SCR is proposed. This study provides a new insight and guidance into the design of low-temperature SCR catalysts resistant to SO2 and H2O in the future.
The Origin of the Size Effect in the Oxidation of CO on Supported Palladium Nanoparticles
Authors: Kaichev Vasily V. , Saraev Andrey A. , Fedorov Aleksandr V. , Gerasimov Evgeny Yu.
Published: November 2023

Two Pd/TiO2 catalysts with mean particle sizes of 1 and 3 nm were prepared and tested in the low-temperature oxidation of CO. It was found that the first catalyst with higher dispersion is more active. Turnover frequencies varied for these catalysts by almost six times. In contrast, the apparent activation energy of the oxidation of CO on the catalyst with smaller Pd nanoparticles was estimated at 76 kJ/mol, and for the catalyst with larger Pd nanoparticles at 58 kJ/mol. According to in situ XANES studies, the particle size effect originates from the oxidation of small palladium nanoparticles under reaction conditions, whereas larger nanoparticles are stable and consist of palladium atoms mainly in the metallic state. Palladium oxide is more active in the low-temperature oxidation of CO than metallic palladium. This means that the origin of size-dependent activity of Pd nanoparticles in the low-temperature oxidation of CO is associated with the change in the chemical composition of nanoparticles that leads to a change in the reaction mechanism and, as a result, in their activity.
ALKBH5 Stabilized N6-Methyladenosine—Modified LOC4191 to Suppress E. coli-Induced Apoptosis
Authors: Xu Haojun , Lin Changjie , Wang Chao , Zhao Tianrui , Yang Jinghan , Zhang Junhao , Hu Yanjun , Qi Xue , Chen Xi , Chen Yingyu , Chen Jianguo , Guo Aizhen , Hu Changmin
Published: November 2023

E. coli is a ubiquitous pathogen that is responsible for over one million fatalities worldwide on an annual basis. In animals, E. coli can cause a variety of diseases, including mastitis in dairy cattle, which represents a potential public health hazard. However, the pathophysiology of E. coli remains unclear. We found that E. coli could induce global upregulation of m6A methylation and cause serious apoptosis in bovine mammary epithelial cells (MAC-T cells). Furthermore, numerous m6A-modified lncRNAs were identified through MeRIP-seq. Interestingly, we found that the expression of LOC4191 with hypomethylation increased in MAC-T cells upon E. coli-induced apoptosis. Knocking down LOC4191 promoted E. coli-induced apoptosis and ROS levels through the caspase 3–PARP pathway. Meanwhile, knocking down ALKBH5 resulted in the promotion of apoptosis through upregulated ROS and arrested the cell cycle in MAC-T cells. ALKBH5 silencing accelerated LOC4191 decay by upregulating its m6A modification level, and the process was recognized by hnRNP A1. Therefore, this indicates that ALKBH5 stabilizes m6A-modified LOC4191 to suppress E. coli-induced apoptosis. This report discusses an initial investigation into the mechanism of m6A-modified lncRNA in cells under E. coli-induced apoptosis and provides novel insights into infectious diseases.
Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
Authors: Zhu Yifan , Shi Hongling , Tang Tian , Li Qianqian , Peng Yongchong , Bermudez Luiz E. , Hu Changmin , Chen Huanchun , Guo Aizhen , Chen Yingyu
Published: November 2023

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette–Guérin (BCG) mutant B1033 that potentially affected mycobacterium pathogenicity. This mutant contained an insertion mutation gene, fadD33, which is involved in lipid metabolism; however, its direct role in regulating M. tb infection is not well understood. Here, we found that the absence of fadD33 reduced BCG adhesion and invasion into human pulmonary alveolar epithelial cells and increased the permeability of the mycobacterial cell wall, allowing M. tb to survive in the low pH and membrane pressure extracellular microenvironment of the host cells. The absence of fadD33 also inhibited the survival of BCG in macrophages by promoting the release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumors necrosis factor-α, through the mitogen-activated protein kinase p38 signaling pathway. Overall, these findings provide new insights into M. tb mechanisms to evade host defenses and might contribute to identifying potential therapeutic and vaccine targets for tuberculosis prevention.
Transcriptome Changes in Glioma Cells upon Infection with the Oncolytic Virus VV-GMCSF-Lact
Authors: Semenov Dmitriy V. , Vasileva Natalia S. , Dymova Maya A. , Mishinov Sergey V. , Savinovskaya Yulya I. , Ageenko Alisa B. , Dome Anton S. , Zinchenko Nikita D. , Stepanov Grigory A. , Kochneva Galina V. , Richter Vladimir A. , Kuligina Elena V.
Published: November 2023

Oncolytic virotherapy is a rapidly evolving approach that aims to selectively kill cancer cells. We designed a promising recombinant vaccinia virus, VV-GMCSF-Lact, for the treatment of solid tumors, including glioma. We assessed how VV-GMCSF-Lact affects human cells using immortalized and patient-derived glioma cultures and a non-malignant brain cell culture. Studying transcriptome changes in cells 12 h or 24 h after VV-GMCSF-Lact infection, we detected the common activation of histone genes. Additionally, genes associated with the interferon-gamma response, NF-kappa B signaling pathway, and inflammation mediated by chemokine and cytokine signaling pathways showed increased expression. By contrast, genes involved in cell cycle progression, including spindle organization, sister chromatid segregation, and the G2/M checkpoint, were downregulated following virus infection. The upregulation of genes responsible for Golgi vesicles, protein transport, and secretion correlated with reduced sensitivity to the cytotoxic effect of VV-GMCSF-Lact. Higher expression of genes encoding proteins, which participate in the maturation of pol II nuclear transcripts and mRNA splicing, was associated with an increased sensitivity to viral cytotoxicity. Genes whose expression correlates with the sensitivity of cells to the virus are important for increasing the effectiveness of cancer virotherapy. Overall, the results highlight molecular markers, biological pathways, and gene networks influencing the response of glioma cells to VV-GMCSF-Lact.