bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifaceted Music Therapy for Depression in Dementia: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Ting Berne , Chen Daniel Tzu-Li , Hsu Wei-Ti , Tsai Chia-Lin , Malau Ikbal Andrian , Lee Sheau-Ling , Jingling Li
Published: February 2024

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = −0.89, 95% Confidence Interval [CI]: −1.48 to −0.30). In contrast, listening to music alone showed a smaller effect (SMD = −0.26, 95% CI: −0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.
Involving Micro and Small Enterprises in the Energy Transition: Evidence from Poland
Authors: Bernat Tomasz , Flaszewska Sylwia , Lisowska Renata , Szymańska Katarzyna
Published: February 2024

The energy transition is one of humanity’s most significant challenges. All micro, small, medium, and large enterprises will have to face it, and some are already making progress. This paper focuses on the involvement of the smallest actors in the energy transition. Micro and small enterprises comprise the largest part of the economy and significantly impact its development. Concerning the broad scope of their activities, these entities are characterized by a specific owner–manager relationship. This means that the final decision is influenced by business objectives, the manager’s approach, their awareness of change, and personal and other factors. Based on the analysis of data from 400 companies, it was found that the involvement of micro and small enterprises in the energy transition is related to their market and financial success.
Multi-Objective Stochastic Paint Optimizer for Solving Dynamic Economic Emission Dispatch with Transmission Loss Prediction Using Random Forest Machine Learning Model
Authors: Sundaram Arunachalam , Alkhaldi Nasser S.
Published: February 2024

Dynamic economic emission dispatch problems are complex optimization tasks in power systems that aim to simultaneously minimize both fuel costs and pollutant emissions while satisfying various system constraints. Traditional methods often involve solving intricate nonlinear load flow equations or employing approximate loss formulas to account for transmission losses. These methods can be computationally expensive and may not accurately represent the actual transmission losses, affecting the overall optimization results. To address these limitations, this study proposes a novel approach that integrates transmission loss prediction into the dynamic economic emission dispatch (DEED) problem. A Random Forest machine learning model was offline-trained to predict transmission losses accurately, eliminating the need for repeated calculations during each iteration of the optimization process. This significantly reduced the computational burden of the algorithm and improved its efficiency. The proposed method utilizes a powerful multi-objective stochastic paint optimizer to solve the highly constrained and complex dynamic economic emission dispatch problem integrated with random forest-based loss prediction. A fuzzy membership-based approach was employed to determine the best compromise Pareto-optimal solution. The proposed algorithm integrated with loss prediction was validated on widely used five and ten-unit power systems with B-loss coefficients. The results obtained using the proposed algorithm were compared with seventeen algorithms available in the literature, demonstrating that the multi-objective stochastic paint optimizer (MOSPO) outperforms most existing algorithms. Notably, for the Institute of Electrical and Electronics Engineers (IEEE) thirty bus system, the proposed algorithm achieves yearly fuel cost savings of USD 37,339.5 and USD 3423.7 compared to the existing group search optimizer algorithm with multiple producers (GSOMP) and multi-objective multi-verse optimization (MOMVO) algorithms.
Fluid-Dynamic Mechanisms Underlying Wind Turbine Wake Control with Strouhal-Timed Actuation
Authors: Cheung Lawrence C. , Brown Kenneth A. , Houck Daniel R. , deVelder Nathaniel B.
Published: February 2024

A reduction in wake effects in large wind farms through wake-aware control has considerable potential to improve farm efficiency. This work examines the success of several emerging, empirically derived control methods that modify wind turbine wakes (i.e., the pulse method, helix method, and related methods) based on Strouhal numbers on the O(0.3). Drawing on previous work in the literature for jet and bluff-body flows, the analyses leverage the normal-mode representation of wake instabilities to characterize the large-scale wake meandering observed in actuated wakes. Idealized large-eddy simulations (LES) using an actuator-line representation of the turbine blades indicate that the n=0 and ±1 modes, which correspond to the pulse and helix forcing strategies, respectively, have faster initial growth rates than higher-order modes, suggesting these lower-order modes are more appropriate for wake control. Exciting these lower-order modes with periodic pitching of the blades produces increased modal growth, higher entrainment into the wake, and faster wake recovery. Modal energy gain and the entrainment rate both increase with streamwise distance from the rotor until the intermediate wake. This suggests that the wake meandering dynamics, which share close ties with the relatively well-characterized meandering dynamics in jet and bluff-body flows, are an essential component of the success of wind turbine wake control methods. A spatial linear stability analysis is also performed on the wake flows and yields insights on the modal evolution. In the context of the normal-mode representation of wake instabilities, these findings represent the first literature examining the characteristics of the wake meandering stemming from intentional Strouhal-timed wake actuation, and they help guide the ongoing work to understand the fluid-dynamic origins of the success of the pulse, helix, and related methods.
Fire Source Determination Method for Underground Commercial Streets Based on Perception Data and Machine Learning
Authors: Yang Yunhao , Zhang Yuanyuan , Zhang Guowei , Tang Tianyao , Ning Zhaoyu , Zhang Zhiwei , Zhao Ziming
Published: February 2024

Determining fire source in underground commercial street fires is critical for fire analysis. This paper proposes a method based on temperature and machine learning to determine information about fire source in underground commercial street fires. Data was obtained through consolidated fire and smoke transport (CFAST) software, and a fire database was established based on the sampling to ascertain fire scenarios. Temperature time series were chosen for feature processing, and three machine learning models for fire source determination were established: decision tree, random forest, and LightGBM. The results indicated that the trained models can determine fire source information based on processed features, achieving a precision exceeding 95%. Among these, the LightGBM model exhibited superior performance, with macro averages of precision, recall, and F1 score being 99.01%, 98.45%, and 99.04%, respectively, and a kappa value of 98.81%. The proposed method for determining the fire source provides technical support for grasping the fire situation in underground commercial streets and has good application prospects.
CNTCB-YOLOv7: An Effective Forest Fire Detection Model Based on ConvNeXtV2 and CBAM
Authors: Xu Yiqing , Li Jiaming , Zhang Long , Liu Hongying , Zhang Fuquan
Published: February 2024

In the context of large-scale fire areas and complex forest environments, the task of identifying the subtle features and aspects of fire can pose a significant challenge for the deep learning model. As a result, to enhance the model’s ability to represent features and its precision in detection, this study initially introduces ConvNeXtV2 and Conv2Former to the You Only Look Once version 7 (YOLOv7) algorithm, separately, and then compares the results with the original YOLOv7 algorithm through experiments. After comprehensive comparison, the proposed ConvNeXtV2-YOLOv7 based on ConvNeXtV2 exhibits a superior performance in detecting forest fires. Additionally, in order to further focus the network on the crucial information in the task of detecting forest fires and minimize irrelevant background interference, the efficient layer aggregation network (ELAN) structure in the backbone network is enhanced by adding four attention mechanisms: the normalization-based attention module (NAM), simple attention mechanism (SimAM), global attention mechanism (GAM), and convolutional block attention module (CBAM). The experimental results, which demonstrate the suitability of ELAN combined with the CBAM module for forest fire detection, lead to the proposal of a new method for forest fire detection called CNTCB-YOLOv7. The CNTCB-YOLOv7 algorithm outperforms the YOLOv7 algorithm, with an increase in accuracy of 2.39%, recall rate of 0.73%, and average precision (AP) of 1.14%.
Effects of Prolonged Fasting and Refeeding on Metabolic, Physiological, Tissue, and Growth Performance Adjustments in Colossoma macropomum
Authors: Porto Lívia de A. , Assis Yhago P. A. S. , Amorim Matheus P. S. , Oliveira Paulo E. C. M. de , Paschoalini Alessandro L. , Bazzoli Nilo , Luz Ronald K. , Favero Gisele C.
Published: February 2024

Fish can tolerate prolonged periods of fasting more easily than endothermic organisms. However, these fasting periods are associated with pronounced lipid and protein catabolism and body weight loss. We evaluated the use of body reserves, growth performance, and the histology of the intestines and muscles of Colossoma macropomum subjected to prolonged fasting for 45 days and refeeding for 14 days. We used 66 juvenile C. macropomum (71.78 ± 10.75 g) distributed in 10 tanks of 100 L in a recirculating aquaculture system (RAS) and kept 6 fish in a separate tank, considered the basal group. The fish were divided into two groups: fed (continuously fed for 59 days) and fasted/refed (subjected to fasting for 45 days and subsequently refed for 14 days). The tambaqui juveniles showed the mobilization of their body reserves during 45 days of fasting but with a large deficit in their growth performance. The 14-day refeeding period was sufficient for fish to restore their energy but insufficient for recovering most growth parameters.
Distinctions of the Emergence of Convective Flows at the “Diffusion–Convections” Boundary in Isothermal Ternary Gas Mixtures with Carbon Dioxide
Authors: Kossov Vladimir , Zhakebayev Dauren , Fedorenko Olga , Zhumali Ainur
Published: February 2024

This study discusses the influence of the composition of a ternary gas mixture on the possibility of occurrence of convective instability under isothermal conditions due to the difference in the diffusion abilities of the components. A numerical study was carried out to study the change in “diffusion–concentration gravitational convection” modes in an isothermal three-component gas mixture He + CO2 − N2. The mixing process in the system under study was modeled at different initial carbon dioxide contents. To carry out a numerical experiment, a mathematical algorithm based on the D2Q9 model of lattice Boltzmann equations was used for modeling the flow of gases. We show that the model presented in the paper allows one to study the occurrence of convective structures at different heavy component contents (carbon dioxide). It has been established that in the system under study, the instability of the mechanical equilibrium occurs when the content of carbon dioxide in the mixture is more than 0.3 mole fractions. The characteristic times for the onset of convective instability and the subsequent creation of structural formations, the values of which depend on the initial content of carbon dioxide in the mixture, have been determined. Distributions of concentration, pressure and kinetic energy that allow one to specify the types of mixing and explain the occurrence of convection for a situation where, at the initial moment of time, the density of the gas mixture in the upper part of the diffusion channel is less than in the lower one, were obtained.
State-Dependent Model Based on Singular Spectrum Analysis Vector for Modeling Structural Breaks: Forecasting Indonesian Export
Authors: Sasmita Yoga , Kuswanto Heri , Prastyo Dedy Dwi
Published: February 2024

Standard time-series modeling requires the stability of model parameters over time. The instability of model parameters is often caused by structural breaks, leading to the formation of nonlinear models. A state-dependent model (SDM) is a more general and flexible scheme in nonlinear modeling. On the other hand, time-series data often exhibit multiple frequency components, such as trends, seasonality, cycles, and noise. These frequency components can be optimized in forecasting using Singular Spectrum Analysis (SSA). Furthermore, the two most widely used approaches in SSA are Linear Recurrent Formula (SSAR) and Vector (SSAV). SSAV has better accuracy and robustness than SSAR, especially in handling structural breaks. Therefore, this research proposes modeling the SSAV coefficient with an SDM approach to take structural breaks called SDM-SSAV. SDM recursively updates the SSAV coefficient to adapt over time and between states using an Extended Kalman Filter (EKF). Empirical results with Indonesian Export data and simulation studies show that the accuracy of SDM-SSAV outperforms SSAR, SSAV, SDM-SSAR, hybrid ARIMA-LSTM, and VARI.
Ultrafast Diffusion Modeling via the Riemann–Liouville Nonlocal Structural Derivative and Its Application in Porous Media
Authors: Xu Wei , Liu Hui , Chen Lijuan , Zhou Yongtao
Published: February 2024

Ultrafast diffusion disperses faster than super-diffusion, and this has been proven by several theoretical and experimental investigations. The mean square displacement of ultrafast diffusion grows exponentially, which provides a significant challenge for modeling. Due to the inhomogeneity, nonlinear interactions, and high porosity of cement materials, the motion of particles on their surfaces satisfies the conditions for ultrafast diffusion. The investigation of the diffusion behavior in cementitious materials is crucial for predicting the mechanical properties of cement. In this study, we first attempted to investigate the dynamic of ultrafast diffusion in cementitious materials underlying the Riemann–Liouville nonlocal structural derivative. We constructed a Riemann–Liouville nonlocal structural derivative ultrafast diffusion model with an exponential function and then extended the modeling strategy using the Mittag–Leffler function. The mean square displacement is analogous to the integral of the corresponding structural derivative, providing a reference standard for the selection of structural functions in practical applications. Based on experimental data on cement mortar, the accuracy of the Riemann–Liouville nonlocal structural derivative ultrafast diffusion model was verified. Compared to the power law diffusion and the exponential law diffusion, the mean square displacement with respect to the Mittag–Leffler law is closely tied to the actual data. The modeling approach based on the Riemann–Liouville nonlocal structural derivative provides an efficient tool for depicting ultrafast diffusion in porous media.
Disparities in Breast Cancer Care—How Factors Related to Prevention, Diagnosis, and Treatment Drive Inequity
Authors: Wilkerson Avia D. , Gentle Corey K. , Ortega Camila , Al-Hilli Zahraa
Published: February 2024

Breast cancer survival has increased significantly over the last few decades due to more effective strategies for prevention and risk modification, advancements in imaging detection, screening, and multimodal treatment algorithms. However, many have observed disparities in benefits derived from such improvements across populations and demographic groups. This review summarizes published works that contextualize modern disparities in breast cancer prevention, diagnosis, and treatment and presents potential strategies for reducing disparities. We conducted searches for studies that directly investigated and/or reported disparities in breast cancer prevention, detection, or treatment. Demographic factors, social determinants of health, and inequitable healthcare delivery may impede the ability of individuals and communities to employ risk-mitigating behaviors and prevention strategies. The disparate access to quality screening and timely diagnosis experienced by various groups poses significant hurdles to optimal care and survival. Finally, barriers to access and inequitable healthcare delivery patterns reinforce inequitable application of standards of care. Cumulatively, these disparities underlie notable differences in the incidence, severity, and survival of breast cancers. Efforts toward mitigation will require collaborative approaches and partnerships between communities, governments, and healthcare organizations, which must be considered equal stakeholders in the fight for equity in breast cancer care and outcomes.
Preserving the Values of Mediterranean Enclosed Fields with Dry Stone Walls, an Example of Vulnerable Natural and Rural Heritage
Authors: López-Estébanez Nieves , Molina-Holgado Pedro , Allende Álvarez Fernando
Published: February 2024

In the continental Mediterranean mountains of the Iberian Peninsula is located a landscape characterized by the presence of enclosed land parcels delimited by dry stone walls or vegetation, or by both these elements. This landscape has been included, since 2018, in UNESCO’s Representative List of Intangible Cultural Heritage of Humanity under the name of Art of dry stone walling, knowledge and techniques. However, today’s territorial dynamics jeopardize the maintenance of this landscape heritage. This work set out to understand their origins, dynamics, and evolution from the 11th century (Middle Ages) to the present using historical documentation from different sources and diachronic cartography from aerial photographs. The fieldwork was designed to identify natural, cultural features and recent dynamics, in particular those related to urbanization changes of the last 70 years. Finally, we delved into the new dynamics of exploitation that were based on extensification and a loss of productive diversity. The results obtained lead us to consider that the loss of this agro-landscape must be prevented, with a reasonable livestock grazing criteria and a rational management of its heritage features. This requires regional, national, and European policies that recognize the enclosed landscape as a heritage ecosystem in which biodiversity and agriculture are closely linked.
Domesticating Colour in the Early Modern Age: Dyeing Wool in Black in Portugal
Authors: Ferreira Luís Gonçalves
Published: February 2024

Mastering a colour—as such, its ‘domestication’—involves a weft of technological and symbolic relationships encompassed in the human ability to reproduce a visible colour using the techniques of textile dyeing. The Regimento dos panos or Regimento dos trapeiros (‘regulation of fabrics’ or ‘regulation of drapers’), published in 1573 and expanded in 1690, is a document made up of 107 chapters aiming to standardise the various stages of the production chain of woollen goods in Portugal. In the sections relating to the finishing of fabrics, the regulation carefully details the dyeing of the colour black. The main aim of this text is to discuss the four recipes presented in that document. The system presupposed a phase exogenous to the rules, since the fabrics had to be previously dyed blue (‘celestial blues’) by means of successive immersions of the cloth in a vat with indigo. The dyeing itself was achieved by mixing mordants and auxiliaries (alum, tartar, iron sulphate, and tannins) with a red dye (madder). The main conclusion is that the formulae presented do not constitute, in their general principles, a characteristic Portuguese methodology. In addition, the article includes an inventory of the raw materials used for dyeing in the Early Modern Age, produced, through a qualitative method, through cross-reference with other manuscript and printed sources, as well as an interpretation of their social and economic importance, and a systematisation of the types of Portuguese wools.
Increasing Concentrations of Arthrospira maxima Sonicated Biomass Yields Enhanced Growth in Basil (Ocimum basilicum, Lamiaceae) Seedlings
Authors: Marín-Marín Camila Andrea , Estrada-Peláez José Alberto , Delgado Naranjo Juan Martín , Zapata Ocampo Paola Andrea
Published: February 2024

The continued increase in human populations and use of chemical fertilizers remain a threat to the health and stability of human–ecological systems worldwide. To ameliorate this problem and achieve long-term food security, a variety of ecofriendly technologies have been developed, including the production of cyanobacteria-based biofertilizers. This technology can be optimized through experiments that assess how plant growth is enhanced under different biofertilizer concentrations (g L−1). In this study, the biofertilizer capabilities of various concentrations of sonicated biomass (0, 2.5, 5, 10, 20, and 40 g L−1) derived from the cyanobacteria Arthrospira maxima on the growth of basil (Ocimum basilicum, Lamiaceae) were assessed, comparing their effectiveness with that of a positive control, a commercial biofertilizer (OptiMar Algas Marinas®) administered at 4 mL L−1. Generally, increased concentrations led to enhanced growth parameters; however, discernible differences from the negative control (0 g L−1) were often observed only when concentrations exceeded 5 g L−1. Surprisingly, the negative and positive controls often yielded similar results. A chemical composition analysis of A. maxima revealed high concentrations of the phytohormones, macronutrients, and essential amino acids that likely explain how our A. maxima sample enhanced growth in basil. Further research is required to determine how other crop plants respond to different concentrations of A. maxima. Additionally, assessing the feasibility of creating an economically accessible product with a higher concentration of A. maxima is crucial for practical applications.
Hydrogen from Waste Gasification
Authors: Rauch Reinhard , Kiros Yohannes , Engvall Klas , Kantarelis Efthymios , Brito Paulo , Nobre Catarina , Santos Santa Margarida , Graefe Philipp A.
Published: February 2024

Hydrogen is a versatile energy vector for a plethora of applications; nevertheless, its production from waste/residues is often overlooked. Gasification and subsequent conversion of the raw synthesis gas to hydrogen are an attractive alternative to produce renewable hydrogen. In this paper, recent developments in R&D on waste gasification (municipal solid waste, tires, plastic waste) are summarised, and an overview about suitable gasification processes is given. A literature survey indicated that a broad span of hydrogen relates to productivity depending on the feedstock, ranging from 15 to 300 g H2/kg of feedstock. Suitable gas treatment (upgrading and separation) is also covered, presenting both direct and indirect (chemical looping) concepts. Hydrogen production via gasification offers a high productivity potential. However, regulations, like frame conditions or subsidies, are necessary to bring the technology into the market.
Neuroprotective Effect of Resveratrol against Manganese-Induced Oxidative Stress and Matrix Metalloproteinase-9 in an “In Vivo” Model of Neurotoxicity
Authors: Latronico Tiziana , Rossano Rocco , Miniero Daniela Valeria , Casalino Elisabetta , Liuzzi Grazia Maria
Published: February 2024

Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl2 in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats. A progressive recovery of body weight was detected in rats co-treated with Mn and RSV. The analysis of brain homogenates indicated that RSV counteracted the Mn-induced increase in MMP-9 levels and reactive oxygen species production as well as the Mn-induced decrease in superoxide dismutase activity and glutathione content. In conclusion, Mn exposure, resulting in MMP-9 induction with mechanisms related to oxidative stress, represents a risk factor for the development of CNS diseases.
The Brown Sugar Mediated Carbon Quantum Dots as a Novel Fluorescence Sensor for Sensitive Detection of Gentamicin and Its Application in Foods
Authors: Guo Xinran , Guo Yanxin , Chen Xinyue
Published: February 2024

In this work, a novel fluorescence sensing strategy was proposed for the detection of gentamicin based on fluorescent carbon quantum dots (CQDs) and gold nanoparticles (AuNPs). Herein, the CQDs were green-synthesized for the first time via a one-step hydrothermal method utilizing brown sugar as the precursor. In the presence of citrate-stabilized AuNPs, the fluorescence of CQDs was quenched efficiently. Gentamicin, on the other hand, had a higher affinity for AuNPs and was able to compete with CQDs for a preferential binding to AuNPs, which ultimately led to the aggregation of AuNPs and freeing of CQDs in solution, causing the fluorescence recovery of CQDs. Based on the above phenomenon, the concentrations of gentamicin could be ascertained by detecting the variations in fluorescence intensity of CQDs. This sensing strategy exhibited excellent selectivity in various antibiotics. At the same time, the method displayed outstanding sensitivity for gentamicin, which was successfully applied to real samples detection.
Extracellular Vesicles in Flaviviridae Pathogenesis: Their Roles in Viral Transmission, Immune Evasion, and Inflammation
Authors: Latanova Anastasia , Karpov Vadim , Starodubova Elizaveta
Published: February 2024

The members of the Flaviviridae family are becoming an emerging threat for public health, causing an increasing number of infections each year and requiring effective treatment. The consequences of these infections can be severe and include liver inflammation with subsequent carcinogenesis, endothelial damage with hemorrhage, neuroinflammation, and, in some cases, death. The mechanisms of Flaviviridae pathogenesis are being actively investigated, but there are still many gaps in their understanding. Extracellular vesicles may play important roles in these mechanisms, and, therefore, this topic deserves detailed research. Recent data have revealed the involvement of extracellular vesicles in steps of Flaviviridae pathogenesis such as transmission, immune evasion, and inflammation, which is critical for disease establishment. This review covers recent papers on the roles of extracellular vesicles in the pathogenesis of Flaviviridae and includes examples of clinical applications of the accumulated data.
Inflammation in Development and Aging: Insights from the Zebrafish Model
Authors: Mastrogiovanni Marta , Martínez-Navarro Francisco Juan , Bowman Teresa V. , Cayuela María L.
Published: February 2024

Zebrafish are an emergent animal model to study human diseases due to their significant genetic similarity to humans, swift development, and genetic manipulability. Their utility extends to the exploration of the involvement of inflammation in host defense, immune responses, and tissue regeneration. Additionally, the zebrafish model system facilitates prompt screening of chemical compounds that affect inflammation. This study explored the diverse roles of inflammatory pathways in zebrafish development and aging. Serving as a crucial model, zebrafish provides insights into the intricate interplay of inflammation in both developmental and aging contexts. The evidence presented suggests that the same inflammatory signaling pathways often play instructive or beneficial roles during embryogenesis and are associated with malignancies in adults.
Sasanquasaponin from Camellia oleifera Abel Exerts an Anti-Inflammatory Effect in RAW 264.7 Cells via Inhibition of the NF-κB/MAPK Signaling Pathways
Authors: Zhao Yaxin , Zhao Nanshan , Kollie Larwubah , Yang Dongfeng , Zhang Xiaodan , Zhang Haihua , Liang Zongsuo
Published: February 2024

Sasanquasaponin (SQS), a secondary metabolite that is derived from Camellia seeds, reportedly possesses notable biological properties. However, the anti-inflammatory effects of SQS and its underlying mechanisms remain poorly explored. Herein, we aimed to investigate the anti-inflammatory properties of SQS against lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells, focusing on the nuclear factor-κB (NF-κB) and MAPK signaling pathways. SQS was isolated using a deep eutectic solvent and D101 macroporous adsorption resin and analyzed using high-performance liquid chromatography. The viability of LPS-stimulated RAW264.7 was assessed using the CCK-8 assay. The presence of reactive oxygen species (ROS) was evaluated using 2′,7′-dichlorofluorescein-diacetate. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected using reverse transcription–quantitative PCR and ELISA. Western blot was performed to analyze the protein expression of LPS-induced RAW264.7 cells. Herein, SQS exhibited anti-inflammatory activity: 30 μg/mL of SQS significantly reduced ROS generation, inhibited the LPS-induced expression of iNOS and COX-2, and attenuated the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. The anti-inflammatory activity was potentially mediated by inhibiting the phosphorylation of IκBα and p65 in the NF-κB signaling pathway and the phosphorylation of ERK and JNK in the MAPK signaling pathway. Accordingly, SQS could inhibit inflammation in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPK signaling pathways. This study demonstrated the potential application of SQS as an anti-inflammatory agent.
Minimal Residual Disease in Acute Myeloid Leukemia: Old and New Concepts
Authors: Chea Mathias , Rigolot Lucie , Canali Alban , Vergez Francois
Published: February 2024

Minimal residual disease (MRD) is of major importance in onco-hematology, particularly in acute myeloid leukemia (AML). MRD measures the amount of leukemia cells remaining in a patient after treatment, and is an essential tool for disease monitoring, relapse prognosis, and guiding treatment decisions. Patients with a negative MRD tend to have superior disease-free and overall survival rates. Considerable effort has been made to standardize MRD practices. A variety of techniques, including flow cytometry and molecular methods, are used to assess MRD, each with distinct strengths and weaknesses. MRD is recognized not only as a predictive biomarker, but also as a prognostic tool and marker of treatment efficacy. Expected advances in MRD assessment encompass molecular techniques such as NGS and digital PCR, as well as optimization strategies such as unsupervised flow cytometry analysis and leukemic stem cell monitoring. At present, there is no perfect method for measuring MRD, and significant advances are expected in the future to fully integrate MRD assessment into the management of AML patients.
Pleiotropic Effects of PhaR Regulator in Bradyrhizobium diazoefficiens Microaerobic Metabolism
Authors: Quelas Juan I. , Cabrera Juan J. , Díaz-Peña Rocío , Sánchez-Schneider Lucía , Jiménez-Leiva Andrea , Tortosa Germán , Delgado María J. , Pettinari M. Julia , Lodeiro Aníbal R. , del Val Coral , Mesa Socorro
Published: February 2024

Bradyrhizobium diazoefficiens can live inside soybean root nodules and in free-living conditions. In both states, when oxygen levels decrease, cells adjust their protein pools by gene transcription modulation. PhaR is a transcription factor involved in polyhydroxyalkanoate (PHA) metabolism but also plays a role in the microaerobic network of this bacterium. To deeply uncover the function of PhaR, we applied a multipronged approach, including the expression profile of a phaR mutant at the transcriptional and protein levels under microaerobic conditions, and the identification of direct targets and of proteins associated with PHA granules. Our results confirmed a pleiotropic function of PhaR, affecting several phenotypes, in addition to PHA cycle control. These include growth deficiency, regulation of carbon and nitrogen allocation, and bacterial motility. Interestingly, PhaR may also modulate the microoxic-responsive regulatory network by activating the expression of fixK2 and repressing nifA, both encoding two transcription factors relevant for microaerobic regulation. At the molecular level, two PhaR-binding motifs were predicted and direct control mediated by PhaR determined by protein-interaction assays revealed seven new direct targets for PhaR. Finally, among the proteins associated with PHA granules, we found PhaR, phasins, and other proteins, confirming a dual function of PhaR in microoxia.
Reticulocyte Antioxidant Enzymes mRNA Levels versus Reticulocyte Maturity Indices in Hereditary Spherocytosis, β-Thalassemia and Sickle Cell Disease
Authors: Melo Daniela , Ferreira Fátima , Teles Maria José , Porto Graça , Coimbra Susana , Rocha Susana , Santos-Silva Alice
Published: February 2024

The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of CAT, GPX1, PRDX2 and SOD1 in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and β-thalassemia (β-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for SOD1. HS, SCD and β-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. β-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia.
Changes in HLA-B27 Transgenic Rat Fecal Microbiota Following Tofacitinib Treatment and Ileocecal Resection Surgery: Implications for Crohn’s Disease Management
Authors: Blondeaux Aurélie , Valibouze Caroline , Speca Silvia , Rousseaux Christel , Dubuquoy Caroline , Blanquart Hélène , Zerbib Philippe , Desreumaux Pierre , Foligné Benoît , Titécat Marie
Published: February 2024

The therapeutic management of Crohn’s disease (CD), a chronic relapsing–remitting inflammatory bowel disease (IBD), is highly challenging. Surgical resection is sometimes a necessary procedure even though it is often associated with postoperative recurrences (PORs). Tofacitinib, an orally active small molecule Janus kinase inhibitor, is an anti-inflammatory drug meant to limit PORs in CD. Whereas bidirectional interactions between the gut microbiota and the relevant IBD drug are crucial, little is known about the impact of tofacitinib on the gut microbiota. The HLA-B27 transgenic rat is a good preclinical model used in IBD research, including for PORs after ileocecal resection (ICR). In the present study, we used shotgun metagenomics to first delineate the baseline composition and determinants of the fecal microbiome of HLA-B27 rats and then to evaluate the distinct impact of either tofacitinib treatment, ileocecal resection or the cumulative effect of both interventions on the gut microbiota in these HLA-B27 rats. The results confirmed that the microbiome of the HLA-B27 rats was fairly different from their wild-type littermates. We demonstrated here that oral treatment with tofacitinib does not affect the gut microbial composition of HLA-B27 rats. Of note, we showed that ICR induced an intense loss of bacterial diversity together with dramatic changes in taxa relative abundances. However, the oral treatment with tofacitinib neither modified the alpha-diversity nor exacerbated significant modifications in bacterial taxa induced by ICR. Collectively, these preclinical data are rather favorable for the use of tofacitinib in combination with ICR to address Crohn’s disease management when considering microbiota.
Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus
Authors: Hristova Svetlana H. , Zhivkov Alexandar M.
Published: February 2024

The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic potential on the surface of the receptor-binding domain (RBD) could be altered, and the S-ACE2 association could become stronger or weaker. The aim of the current research is to investigate whether point mutations can noticeably alter the electrostatic potential on the RBD and the 3D stability of the S1-subunit of the S-protein. For this purpose, 15 mutants with different hydrophilicity and electric charge (positive, negative, or uncharged) of the substituted and substituting amino acid residues, located on the RBD at the S1-ACE2 interface, are selected, and the 3D structure of the S1-subunit is reconstructed on the base of the crystallographic structure of the S-protein of the wild-type strain and the amino acid sequence of the unfolded polypeptide chain of the mutants. Then, the Gibbs free energy of folding, isoelectric point, and pH-dependent surface electrostatic potential of the S1-subunit are computed using programs for protein electrostatics. The results show alterations in the local electrostatic potential in the vicinity of the mutant amino acid residue, which can influence the S-ACE2 association. This approach allows prediction of the relative infectivity, transmissibility, and contagiousness (at equal social immune status) of new SARS-CoV-2 mutants by reconstruction of the 3D structure of the S1-subunit and calculation of the surface electrostatic potential.
Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy—A Narrative Review
Authors: Dimitrov George , Mangaldzhiev Radoslav , Slavov Chavdar , Popov Elenko
Published: February 2024

After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis’ accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis’ efficacy in the intricate landscape of mCRPC.
Carbon–TiO2 Hybrid Quantum Dots for Photocatalytic Inactivation of Gram-Positive and Gram-Negative Bacteria
Authors: Dong Xiuli , Liu Yamin , Adcock Audrey F. , Sheriff Kirkland , Liang Weixiong , Yang Liju , Sun Ya-Ping
Published: February 2024

Carbon–semiconductor hybrid quantum dots are classical carbon dots with core carbon nanoparticles doped with a selected nanoscale semiconductor. Specifically, on those with the nanoscale TiO2 doping, denoted as CTiO2-Dots, their synthesis and thorough characterization were reported previously. In this work, the CTiO2-Dots were evaluated for their visible light-activated antibacterial function, with the results showing the effective killing of not only Gram-positive but also the generally more resistant Gram-negative bacteria. The hybrid dots are clearly more potent antibacterial agents than their neat carbon dot counterparts. Mechanistically, the higher antibacterial performance of the CTiO2-Dots is attributed to their superior photoexcited state properties, which are reflected by the observed much brighter fluorescence emissions. Also considered and discussed is the possibility of additional contributions to the antibacterial activities due to the photosensitization of the nanoscale TiO2 by its doped core carbon nanoparticles.
Overexpression of Aurora Kinase B Is Correlated with Diagnosis and Poor Prognosis in Hepatocellular Carcinoma
Authors: Zhang Jin , Ma Jiaxiu , Li Yalan , An Yaxin , Du Wei , Yang Qun , Huang Meiling , Cai Xuefei
Published: February 2024

Aurora kinase B (AURKB) overexpression promotes tumor initiation and development by participating in the cell cycle. In this study, we focused on the mechanism of AURKB in hepatocellular carcinoma (HCC) progression and on AURKB’s value as a diagnostic and prognostic biomarker in HCC. We used data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to analyze AURKB expression in HCC. We found that the expression levels of AURKB in HCC samples were higher than those in the corresponding control group. R packages were used to analyze RNA sequencing data to identify AURKB-related differentially expressed genes (DEGs), and these genes were found to be significantly enriched during the cell cycle. The biological function of AURKB was verified, and the results showed that cell proliferation was slowed down and cells were arrested in the G2/M phase when AURKB was knocked down. AURKB overexpression resulted in significant differences in clinical symptoms, such as the clinical T stage and pathological stage. Kaplan–Meier survival analysis, Cox regression analysis, and Receiver Operating Characteristic (ROC) curve analysis suggested that AURKB overexpression has good diagnostic and prognostic potential in HCC. Therefore, AURKB may be used as a potential target for the diagnosis and cure of HCC.
Dimeric Tubulin Modifies Mechanical Properties of Lipid Bilayer, as Probed Using Gramicidin A Channel
Authors: Rostovtseva Tatiana K. , Weinrich Michael , Jacobs Daniel , Rosencrans William M. , Bezrukov Sergey M.
Published: February 2024

Using the gramicidin A channel as a molecular probe, we show that tubulin binding to planar lipid membranes changes the channel kinetics—seen as an increase in the lifetime of the channel dimer—and thus points towards modification of the membrane’s mechanical properties. The effect is more pronounced in the presence of non-lamellar lipids in the lipid mixture used for membrane formation. To interpret these findings, we propose that tubulin binding redistributes the lateral pressure of lipid packing along the membrane depth, making it closer to the profile expected for lamellar lipids. This redistribution happens because tubulin perturbs the lipid headgroup spacing to reach the membrane’s hydrophobic core via its amphiphilic α-helical domain. Specifically, it increases the forces of repulsion between the lipid headgroups and reduces such forces in the hydrophobic region. We suggest that the effect is reciprocal, meaning that alterations in lipid bilayer mechanics caused by membrane remodeling during cell proliferation in disease and development may also modulate tubulin membrane binding, thus exerting regulatory functions. One of those functions includes the regulation of protein–protein interactions at the membrane surface, as exemplified by VDAC complexation with tubulin.
Ectopic Expression of PtrLBD39 Retarded Primary and Secondary Growth in Populus trichocarpa
Authors: Yu Jing , Gao Boyuan , Li Danning , Li Shuang , Chiang Vincent L. , Li Wei , Zhou Chenguang
Published: February 2024

Primary and secondary growth of trees are needed for increments in plant height and stem diameter, respectively, affecting the production of woody biomass for applications in timber, pulp/paper, and related biomaterials. These two types of growth are believed to be both regulated by distinct transcription factor (TF)-mediated regulatory pathways. Notably, we identified PtrLBD39, a highly stem phloem-specific TF in Populus trichocarpa and found that the ectopic expression of PtrLBD39 in P. trichocarpa markedly retarded both primary and secondary growth. In these overexpressing plants, the RNA-seq, ChIP-seq, and weighted gene co-expression network analysis (WGCNA) revealed that PtrLBD39 directly or indirectly regulates TFs governing vascular tissue development, wood formation, hormonal signaling pathways, and enzymes responsible for wood components. This regulation led to growth inhibition, decreased fibrocyte secondary cell wall thickness, and reduced wood production. Therefore, our study indicates that, following ectopic expression in P. trichocarpa, PtrLBD39 functions as a repressor influencing both primary and secondary growth.
Bruton’s Tyrosine Kinase Inhibitors: Recent Updates
Authors: Fares Amneh , Carracedo Uribe Carlos , Martinez Diana , Rehman Tauseef , Silva Rondon Carlos , Sandoval-Sus Jose
Published: February 2024

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the landscape for the treatment of hematological malignancies, solid tumors, and, recently, autoimmune disorders. The BTK receptor is expressed in several hematopoietic cells such as macrophages, neutrophils, mast cells, and osteoclasts. Similarly, the BTK receptor is involved in signaling pathways such as chemokine receptor signaling, Toll-like receptor signaling, and Fc receptor signaling. Due to their unique mechanism, these agents provide a diverse utility in a variety of disease states not limited to the field of malignant hematology and are generally well-tolerated.