bluuebunny/crossref_metadata_2025 huggingface dataset:
Coconut Fatty Acid Distillate Ca-Soap with Different Calcium Sources: Effects of Varied Proportions of Protected and Unprotected Fat Supplementation in Dairy Rations
Authors: Zahera Rika , Pratiwi Mega Indah , Fitri Ainissya , Koike Satoshi , Permana Idat Galih , Despal
Published: September 2024

This study aimed to compare calcium oxide (CaO) and calcium chloride (CaCl2) as calcium sources for coconut fatty acid distillate (CFAD) calcium soap (Ca-soap) production and to evaluate the supplementation ratios of unprotected and protected CFAD in dairy rations to optimize rumen function. This research included two steps: (1) assessing the protection strength of Ca-soap made with CaO and CaCl2 at mole ratios of Ca to CFAD of 1, 1.5, 2, and 2.5; (2) evaluating CFAD supplementation in an in vitro dairy ration study using a 5 × 4 randomized factorial block design. Factor A compared unprotected and protected CFAD ratios of A1 = 100:0, A2 = 75:25, A3 = 50:50, A4 = 25:75, and A5 = 0:100, and factor B compared supplementation levels of B1 = 0%, B2 = 1%, B3 = 2%, and B4 = 3%. CaCl2 at a 2.5-mole ratio to CFAD produced the lowest acid value and the carboxylic acid (C=O) chemical bond. Complete protection (0:100) exhibited the highest densities of Bacteroides and nutrient digestibility (p < 0.05) without significantly affecting rumen fermentability (p > 0.05). Higher CFAD levels significantly reduced methanogens and protozoa (p < 0.05) without significantly affecting estimated methane production. In conclusion, CaCl2 at a 2.5-mole ratio to CFAD provided the best protection, and its complete protection in CFAD supplementation optimized rumen function.
Fat Profiles of Milk and Butter Obtained from Different Dairy Systems (High and Low Pasture) and Seasons (Spring and Fall): Focus on Healthy Fatty Acids and Technological Properties of Butter
Authors: Grille Lucía , Vieitez Ignacio , Garay Andrea , Romero Melissa , Jorcín Santiago , Krall Esteban , Méndez Maria Noel , Irigaray Bruno , Bejarano Edinson , López-Pedemonte Tomás
Published: September 2024

This study aimed to evaluate the fatty acid (FA) profile in milk from commercial farms with varying pasture levels in the diet during spring and fall, and to investigate the physical and chemical properties of butter to assess the impact of FAs on technological and nutritional properties. Milk sampling was conducted biweekly from six farms, categorized into high (HP) and low (LP) pasture treatments based on pasture intake: >60% and <35%, respectively. Butter was made from a pasture-based system (GRZ) and a confined system (C). No differences were observed in milk fat percentage between HP and LP in either season. High pasture had 85–66% more conjugated linoleic acid (CLA, p = 0.01), 74–48% more trans-vaccenic acid (TVA, p = 0.01), and 21–15% more branched-chain FAs (BCFAs, p = 0.006) than LP in spring and fall, respectively. In fall, butter from C had lower saturated FAs (SFAs, p = 0.005), higher unsaturated FAs (UFA, p = 0.008), and a lower spreadability index (SI, p = 0.005) than GRZ, resulting in softer butter. In conclusion, HP in both seasons had higher contents of FAs considered healthy for consumers compared to LP. Contrary to expectations, in fall, C showed higher UFAs and lower SFAs in butter, leading to better technological characteristics than GRZ.
[68Ga]Ga-DOTAGA-Glu(FAPi)2 Shows Enhanced Tumor Uptake and Theranostic Potential in Preclinical PET Imaging
Authors: Mortensen Julie van Krimpen , Mattiussi Simona , Hvass Lars , Lund Emilie Graae , Shalgunov Vladimir , Roesch Frank , Battisti Umberto Maria , Herth Matthias Manfred , Kjaer Andreas
Published: September 2024

The use of fibroblast activation protein inhibitors (FAPis) for positron emission tomography (PET) imaging in cancer has garnered significant interest in recent years, yielding promising results in preclinical and clinical settings. FAP is predominantly expressed in pathological conditions such as fibrosis and cancer, making it a compelling target. An optimized approach involves using FAPi homodimers as PET tracers, which enhance tumor uptake and retention, making them more effective candidates for therapy. Here, a UAMC-1110 inhibitor-based homodimer, DOTAGA-Glu(FAPi)2, was synthesized and radiolabeled with gallium-68, and its efficacy was evaluated in vivo for PET imaging in an endogenously FAP-expressing xenografted mouse model, U87MG. Notably, 45 min post-injection, the mean uptake of [68Ga]Ga-DOTAGA-Glu(FAPi)2 was 4.7 ± 0.5% ID/g in the tumor with low off-target accumulation. The ex vivo analysis of the FAP expression in the tumors confirmed the in vivo results. These findings highlight and confirm the tracer’s potential for diagnostic imaging of cancer and as a theranostic companion.
Portal Vein Pulsatility: A Valuable Approach for Monitoring Venous Congestion and Prognostic Evaluation in Acute Decompensated Heart Failure
Authors: Grigore Mihai , Grigore Andreea-Maria , Ilieșiu Adriana-Mihaela
Published: September 2024

Background: The severity of systemic congestion is associated with increased portal vein flow pulsatility (PVP). Aim: To determine the usefulness of PVP as a marker of decongestion and prognosis in acute decompensated heart failure (ADHF) patients. Methods: 105 patients, 60% of whom were men, were hospitalized with ADHF, and their PVP index (PVPI) was calculated (maximum velocity–minimum velocity/maximum velocity) × 100 on admission and before discharge, along with their EVEREST score, inferior vena cava diameter (IVC), NT-proBNP, serum sodium, and glomerular filtration rate. A PVPI ≥ 50% was defined as a marker of systemic congestion. After treatment with loop diuretics, a decrease in PVPI of >50% before discharge was considered a marker of decongestion The patients were classified into two groups (G): G1-PVPI decrease ≥ 50% (54 patients) and G2-PVPI decrease < 50% (51 patients). Results: At discharge, compared to G2, G1 patients had lower mean PVPI (14.2 vs. 38.9; p < 0.001), higher serum Na (138 vs. 132 mmol/L, p = 0.03), and a higher number of patients with a significant (>30%) NT-proBNP decrease (42 vs. 27, p = 0.007). PVPI correlated with IVC (r = 0.55, p < 0.001), NT-proBNP (r = 0.21, p = 0.04), and serum Na (r = −0.202, p = 0.04). A total of 55% of patients had worsening renal failure (G1 63% vs. G2 48%, p = 0.17). After 90 days, G2 patients had higher mortality (27.45% vs. 3.7 p = 0.001) and rehospitalization (49.01% vs. 33.33%, p < 0.001). In multivariate regression analysis, PVPI was an independent predictor of rehospitalization (OR 1.05, 95% CI 1.00–1.10, p = 0.048). Conclusions: Portal vein flow pulsatility, a meaningful marker of persistent subclinical congestion, is related to short-term prognosis in ADHF patients.
The Impact of the COVID-19 Pandemic on Melanoma Diagnosis: A Single-Center Study
Authors: Sabău Adrian-Horațiu , Cocuz Iuliu-Gabriel , Niculescu Raluca , Tinca Andreea Cătălina , Szoke Andreea Raluca , Lazar Bianca-Andreea , Chiorean Diana Maria , Cotoi Ovidiu Simion
Published: September 2024

(1) Background: Melanoma represents the most aggressive form of skin cancer, with an increasing incidence and numerous risk factors. The COVID-19 pandemic has led to modifications in work protocols. This study aims to elucidate potential changes in the number and characteristics of primary melanomas diagnosed in the Pathology Department of the Târgu Mureș County Clinical Hospital before, during, and after the COVID-19 pandemic. (2) Methods: This study included 140 patients grouped into six periods: two pre-COVID-19 periods, the COVID-19 pandemic period, and three post-COVID-19 periods. Epidemiological data, diagnoses, and histopathological reports were analyzed. (3) Results: The number of cases diagnosed during the COVID-19 pandemic was significantly lower than in the other analyzed periods. Regarding the monitored parameters, a statistically significant increase was observed in the first two post-COVID-19 periods, with a return to values similar to those of the first period in the last analyzed period. Additionally, a statistically significant increase in the incidence of distant metastases was identified in the post-COVID-19 periods. (4) Conclusions: The COVID-19 pandemic had a negative impact on the diagnosis of new melanoma cases, leading to an increase in the number of cases and a worsening of prognostic parameters.
Optimal Placement and Sizing of Battery Energy Storage Systems for Improvement of System Frequency Stability
Authors: Parajuli Amrit , Gurung Samundra , Chapagain Kamal
Published: September 2024

Modern power systems are growing in complexity due to the installation of large generators, long transmission lines, the addition of inertialess renewable energy resources (RESs) with zero inertia, etc., which can all severely degrade the system frequency stability. This can lead to under-/over-frequency load shedding, damage to turbine blades, and affect frequency-sensitive loads. In this study, we propose a methodology to improve the two critical frequency stability indices, i.e., the frequency nadir and the rate of change of frequency (RoCoF), by formulating an optimization problem. The size and placement location of battery energy storage systems (BESSs) are considered to be the constraints for the proposed optimization problem. Thereafter, the optimization problem is solved using the three metaheuristic optimization algorithms: the particle swarm optimization, firefly, and bat algorithm. The best performing algorithm is then selected to find the optimal sizing and placement location of the BESSs. The analyses are all performed on the IEEE 9-bus and IEEE 39-bus test systems. Several scenarios which consider multiple generator outages, increased/decreased loading conditions, and the addition of RESs are also considered for both test systems in this study. The obtained results show that under all scenarios, the proposed method can enhance system frequency compared to the existing method and without BESSs. The proposed method can be easily upscaled for a larger electrical network for obtaining the optimized BESS size and location for the improvement of the system frequency stability.
Methodological Planning to Determine the Technological Expansion of Smart Metering Systems for Utilities
Authors: Toledo-Orozco Marco , Morales Jadán Diego , Arévalo Lozado Sebastián , Álvarez Bel Carlos
Published: September 2024

This research uses data analysis and mining techniques to determine the technological expansion of measurement systems in a public service company. It integrates technical, economic, geographic, and social variables into the analysis using machine learning techniques to discover patterns and relationships in large data sets. The fuzzy logic methodology is applied using the MATLAB programming tool “Fuzzy Logic” to build algorithms that allow for the correct selection of measurement, achieving greater efficiency and precision in the assignment of meter types. The results show that 98% of the metering systems in the significant part are electronic meters, with the “Residential BT” rate being the most extensive data set. Implementing the “fuzzy logic” technique recognizes that more than 60% of the meters are electronic, with the registration of active energy, reactive energy, and demand, allowing for greater control over the marketing variables of the distribution system operator. This research suggests that a future restructuring of electrical metering systems benefits the company and its users. By applying the analysis, a portfolio of viable projects for the replacement of measurement systems is obtained, and they are grouped into two clusters based on the total cost of the technological change.
A Study on the Effects of Vacuum, Nitrogen, and Air Heat Treatments on Single-Chain Cellulose Based on a Molecular Dynamics Simulation
Authors: Hua Youna , Wang Wei , Gao Jingying , Li Ning , Qu Zening
Published: September 2024

Employing molecular dynamics software, three models—vacuum–cellulose, nitrogen–cellulose, and air–cellulose—were built to clarify, via a microscopic perspective, the macroscopic changes in single-chain cellulose undergoing vacuum, nitrogen, and air heat treatments. Kinetic simulations were run following model equilibrium within the NPT system of 423, 443, 463, 483, and 503 K. The energy variations, cell parameters, densities, mean square displacements, hydrogen bonding numbers, and mechanical parameters were analyzed for the three models. The findings demonstrate that as the temperature climbed, the cellular characteristics among two models—the nitrogen and vacuum models—decreased and subsequently increased. The nitrogen model reached its lowest value at 443 K. In contrast, the vacuum model reached its minimum value at 463 K. The vacuum heat treatment may enhance the structural stability of the single-chain cellulose more effectively than the nitrogen and air treatments because it increases the number of hydrogen bonds within the cellulose chain and stabilizes the mean square displacement. Furthermore, the temperature has an impact on the mechanical characteristics of the cellulose amorphous zone; the maximum values of E and G for the vacuum and nitrogen models are found at 463 and 443 K, respectively. The Young’s modulus and shear modulus were consistently more significant for the vacuum model at either temperature, and the Poisson’s ratio was the opposite. Therefore, the vacuum heat treatment can better maintain wood stiffness and deformation resistance, thus improving wood utilization. These findings provide an essential theoretical basis for wood processing and modification, which can help optimize the heat treatment and enhance wood’s utilization and added value.
Parallel and Distributed Frugal Tracking of a Quantile
Authors: Epicoco Italo , Pulimeno Marco , Cafaro Massimo
Published: September 2024

In this paper, we deal with the problem of monitoring network latency. Indeed, latency is a key network metric related to both network performance and quality of service, since it directly impacts on the overall user’s experience. High latency leads to unacceptably slow response times of network services, and may increase network congestion and reduce the throughput, in turn disrupting communications and the user’s experience. A common approach to monitoring network latency takes into account the frequently skewed distribution of latency values, and therefore specific quantiles are monitored, such as the 95th, 98th, and 99th percentiles. We present a comparative analysis of the speed of convergence of the sequential FRUGAL-1U, FRUGAL-2U, and EASYQUANTILE algorithms and the design and analysis of parallel, message-passing-based versions of these algorithms that can be used for monitoring network latency quickly and accurately. Distributed versions are also discussed. Extensive experimental results are provided and discussed as well.
A Data-Driven Multi-Step Flood Inundation Forecast System
Authors: Schmid Felix , Leandro Jorge
Published: September 2024

Inundation maps that show water depths that occur in the event of a flood are essential for protection. Especially information on timings is crucial. Creating a dynamic inundation map with depth data in temporal resolution is a major challenge and is not possible with physical models, as these are too slow for real-time predictions. To provide a dynamic inundation map in real-time, we developed a data-driven multi-step inundation forecast system for fluvial flood events. The forecast system is based on a convolutional neural network (CNN), feature-informed dense layers, and a recursive connection from the predicted inundation at timestep t as a new input for timestep t + 1. The forecast system takes a hydrograph as input, cuts it at desired timesteps (t), and outputs the respective inundation for each timestep, concluding in a dynamic inundation map with a temporal resolution (t). The prediction shows a Critical Success Index (CSI) of over 90%, an average Root Mean Square Error (RMSE) of 0.07, 0.12, and 0.15 for the next 6 h, 12 h, and 24 h, respectively, and an individual RMSE value below 0.3 m, for all test datasets when compared with the results from a physically based model.
First Evidence of Reproductive Strategies in Cephalopods Preserved in Phosphate and Siderite Nodules from the Devonian of Uruguay
Authors: Piñeiro Graciela , Rodao Magela , Núñez Demarco Pablo
Published: September 2024

Uruguayan ammonoids are preserved in phosphate and siderite nodules found at the basalmost tillite-like conglomerates of the San Gregorio Formation. This lithostratigraphic unit was deposited under glacial conditions and its age (as well as that of the nodules) has been highly debated because glaciations were intermittent in Gondwana during the Late Paleozoic. Reef-builder organisms (e.g., Rugosa and Tabulata), goniatite and orthoceratid cephalopods, brachiopods, sponges, actinopterygians and other indeterminate gnatostomes, as well as fragmentary stems and roots of cf. Lycopsida are the most frequent fossils in the nodules. According to new biostratigraphic and paleoclimatic evidence, these taxa are representative of a reefal environment of a preliminary Devonian age including species that are common in the underlying Early Devonian (Emsian) Durazno Group. Among the ammonoid remains, more than 40 clusters of hatchling goniatites were found in the nodules. Each cluster contains a variable number of shells similar in shape to some of the adults also preserved within the nodules, representing a single species preserved at the same developmental stage (3 mm on size average). The strongly packed shells are enveloped by a substance with a different chemical composition and microstructure with respect to that of the nodule matrix, possibly indicating the presence of a gelatinous-like substance reminiscent of that secreted by the females of some extant cuttlefish and octopuses at the time of the egg spawn. Differing from previously described ammonoid accumulations, our clusters are unique in containing individuals of just a single species preserved in the same ontogenetic stage. That allows us to suggest that they represent a mode of reproduction in which hatchlings were morphologically similar to their parents and occupied the same habitat. Our results are thus one of the oldest known records of reproductive strategies in Paleozoic ammonoids and the phosphate and siderite nodules from the San Gregorio Formation are here classified as a new Konservat-Lagerstätte, which is the oldest known for South America.
CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease
Authors: Beckers Lien , Rashid Mamunur , Lee Annie J. , Chatila Zena K. , Tamucci Kirstin A. , Talcoff Ryan C. , Hall Jennifer L. , Bennett David A. , Vardarajan Badri N. , Bradshaw Elizabeth M.
Published: September 2024

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer’s disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer’s disease. Several studies explored the molecular outcomes of genetic variation at the CD33 locus. It has been determined that the risk variant associated with AD increases the expression of the large isoform of CD33 (CD33M) in innate immune cells and alters its biological functions. CD33 is thought to signal via the interaction of its ITIM motif and the protein tyrosine phosphatase, SHP-1. Here, we utilize different molecular and computational approaches to investigate how AD-associated genetic variation in CD33 affects its interaction with SHP-1 in human microglia and microglia-like cells. Our findings demonstrate a genotype-dependent interaction between CD33 and SHP-1, which may functionally contribute to the AD risk associated with this CD33 variant. We also found that CD33-PTPN6 (SHP-1) gene–gene interactions impact AD-related traits, while CD33-PTPN11 (SHP-2) interactions do not.
A Comparative Analysis of Oral Health and Self-Rated Health: ‘All of Us Research Program’ vs. ‘Health and Retirement Study’
Authors: Weintraub Jane A. , Moss Kevin L. , Finlayson Tracy L. , Jones Judith A. , Preisser John S.
Published: September 2024

Poor oral health can impact overall health. This study assessed the association between dental factors (dentate status and dental utilization) and self-rated health (S-RH) among older adults in two cross-sectional datasets: (1) NIH “All of Us (AoU) Research Program” (May 2018—July 2022 release) and (2) U.S. nationally representative “Health and Retirement Study” (HRS) 2018 wave. Participants aged ≥ 51 years were included in these analyses if (1) from AoU, they had clinical dental and medical data from electronic health records (EHRs) and surveys (n = 5480), and (2) from HRS, they had dental and socio-demographic survey data (n = 14,358). S-RH was dichotomized (fair/poor vs. better) and analyzed with logistic regression. Sample survey weights for HRS and stratification and averaging AoU results used the weighted HRS race–ethnicity and age distribution standardized respective analyses to the U.S. population. Fair/poor S-RH was reported by 32.6% in AoU and 28.6% in HRS. Dentate status information was available from 7.7% of AoU EHRs. In population-standardized analyses, lack of dental service use increased odds of fair/poor S-RH in AoU, OR (95% CI) = 1.28 (1.11–1.48), and in HRS = 1.45 (1.09–1.94), as did having diabetes, less education, and ever being a smoker. Having no natural teeth was not statistically associated with fair/poor S-RH. Lack of dental service was positively associated with fair/poor S-RH in both datasets. More and better oral health information in AoU and HRS are needed.
Serum-Free Media Formulation Using Marine Microalgae Extracts and Growth Factor Cocktails for Madin-Darby Canine Kidney and Vero Cell Cultures
Authors: Park Areumi , Lee Yeon-Ji , Jo Eunyoung , Park Gun-Hoo , Heo Seong-Yeong , Koh Eun-Jeong , Lee Seung-Hong , Cha Seon-Heui , Heo Soo-Jin
Published: September 2024

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.
The NF-κB1/p50 Subunit Influences the Notch/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia
Authors: Abdollahzadeh Behnaz , Cantale Aeo Noemi Martina , Giordano Nike , Orlando Andrea , Basciani Maria , Peruzzi Giovanna , Grazioli Paola , Screpanti Isabella , Felli Maria Pia , Campese Antonio Francesco
Published: September 2024

T-cell acute lymphoblastic leukemia is an aggressive neoplasia due to hyper-proliferation of lymphoid progenitors and lacking a definitive cure to date. Notch-activating mutations are the most common in driving disease onset and progression, often in combination with sustained activity of NF-κB. Myeloid-derived suppressor cells represent a mixed population of immature progenitors exerting suppression of anti-cancer immune responses in the tumor microenvironment of many malignancies. We recently reported that in a transgenic murine model of Notch3-dependent T-cell acute lymphoblastic leukemia there is an accumulation of myeloid-derived suppressor cells, dependent on both Notch signaling deregulation and IL-6 production inside tumor T-cells. However, possible interaction between NF-κB and Notch in this context remains unexplored. Interestingly, we also reported that Notch3 transgenic and NF-κB1/p50 deleted double mutant mice display massive myeloproliferation. Here, we demonstrated that the absence of the p50 subunit in these mice dramatically enhances the induction and suppressive function of myeloid-derived suppressor cells. This runs in parallel with an impressive increase in IL-6 concentration in the peripheral blood serum, depending on IL-6 hyper-production by tumor T-cells from double mutant mice. Mechanistically, IL-6 increase relies on loss of the negative control exerted by the p50 subunit on the IL-6 promoter. Our results reveal the Notch/NF-κB cross-talk in regulating myeloid-derived suppressor cell biology in T-cell leukemia, highlighting the need to consider carefully the pleiotropic effects of NF-κB-based therapy on the tumor microenvironment.
The ABCG2 Transporter Affects Plasma Levels, Tissue Distribution and Milk Secretion of Lumichrome, a Natural Derivative of Riboflavin
Authors: Millán-García Alicia , Álvarez-Fernández Laura , Blanco-Paniagua Esther , Álvarez Ana I. , Merino Gracia
Published: September 2024

The ABCG2 membrane transporter affects bioavailability and milk secretion of xenobiotics and natural compounds, including vitamins such as riboflavin. We aimed to characterize the in vitro and in vivo interaction of ABCG2 with lumichrome, the main photodegradation product of riboflavin, which has proven in vitro anti-cancer activity and a therapeutical role in antibacterial photodynamic therapy as an efficient photosensitizer. Using MDCK-II polarized cells overexpressing murine Abcg2 and human ABCG2 we found that lumichrome was efficiently transported by both variants. After lumichrome administration to wild-type and Abcg2-/- mice, plasma AUC20–120 min was 1.8-fold higher in Abcg2-/- mice compared with wild-type mice. The liver and testis from Abcg2-/- mice showed significantly higher lumichrome levels compared with wild-type, whereas lumichrome accumulation in small intestine content of wild-type mice was 2.7-fold higher than in Abcg2-/- counterparts. Finally, a 4.1-fold-higher lumichrome accumulation in milk of wild-type versus Abcg2-/- mice was found. Globally, our results show that ABCG2 plays a crucial role in plasma levels, tissue distribution and milk secretion of lumichrome potentially conditioning its biological activity.
Thermophilic Hemicellulases Secreted by Microbial Consortia Selected from an Anaerobic Digester
Authors: Bombardi Luca , Orlando Marco , Aulitto Martina , Fusco Salvatore
Published: September 2024

The rise of agro-industrial activities over recent decades has exponentially increased lignocellulose biomasses (LCB) production. LCB serves as a cost-effective source for fermentable sugars and other renewable chemicals. This study explores the use of microbial consortia, particularly thermophilic consortia, for LCB deconstruction. Thermophiles produce stable enzymes that retain activity under industrial conditions, presenting a promising approach for LCB conversion. This research focused on two microbial consortia (i.e., microbiomes) that were analyzed for enzyme production using a cheap medium, i.e., a mixture of spent mushroom substrate (SMS) and digestate. The secreted xylanolytic enzymes were characterized in terms of temperature and pH optima, thermal stability, and hydrolysis products from LCB-derived polysaccharides. These enzymes showed optimal activity aligning with common biorefinery conditions and outperformed a formulated enzyme mixture in thermostability tests in the digestate. Phylogenetic and genomic analyses highlighted the genetic diversity and metabolic potential of these microbiomes. Bacillus licheniformis was identified as a key species, with two distinct strains contributing to enzyme production. The presence of specific glycoside hydrolases involved in the cellulose and hemicellulose degradation underscores these consortia’s capacity for efficient LCB conversion. These findings highlight the potential of thermophilic microbiomes, isolated from an industrial environment, as a robust source of robust enzymes, paving the way for more sustainable and cost-effective bioconversion processes in biofuel and biochemical production and other biotechnological applications.
Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS
Authors: Hernandez-Navarro Ignacio , Botana Laura , Diez-Mata Javier , Tesoro Laura , Jimenez-Guirado Beatriz , Gonzalez-Cucharero Claudia , Alcharani Nunzio , Zamorano Jose Luis , Saura Marta , Zaragoza Carlos
Published: September 2024

Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-β-Gal was quantified by β-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO−) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response.
Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status
Authors: Bedore Stacy , van der Eerden Joshua , Boghani Faizan , Patel Saloni J. , Yassin Samer , Aguilar Karina , Lokeshwar Vinata B.
Published: September 2024

The clinical outcome of patients with muscle-invasive bladder cancer (MIBC) is poor despite the approval of neoadjuvant chemotherapy or immunotherapy to improve overall survival after cystectomy. MIBC subtypes, immune, transcriptome, metabolomic signatures, and mutation burden have the potential to predict treatment response but none have been incorporated into clinical practice, as tumor heterogeneity and lineage plasticity influence their efficacy. Using the PRISMA statement, we conducted a systematic review of the literature, involving 135 studies published within the last five years, to identify studies reporting on the prognostic value of protein-based biomarkers for response to neoadjuvant therapy in patients with MIBC. The studies were grouped based on biomarkers related to molecular subtypes, cancer stem cell, actin-cytoskeleton, epithelial–mesenchymal transition, apoptosis, and tumor-infiltrating immune cells. These studies show the potential of protein-based biomarkers, especially in the spatial context, to reduce the influence of tumor heterogeneity on a biomarker’s prognostic capability. Nevertheless, currently, there is little consensus on the methodology, reagents, and the scoring systems to allow reliable assessment of the biomarkers of interest. Furthermore, the small sample size of several studies necessitates the validation of potential prognostic biomarkers in larger multicenter cohorts before their use for individualizing neoadjuvant therapy regimens for patients with MIBC.
Cellular and Immunological Analysis of 2D2/Th Hybrid Mice Prone to Experimental Autoimmune Encephalomyelitis in Comparison with 2D2 and Th Lines
Authors: Aulova Kseniya S. , Urusov Andrey E. , Chernyak Aleksander D. , Toporkova Ludmila B. , Chicherina Galina S. , Buneva Valentina N. , Orlovskaya Irina A. , Nevinsky Georgy A.
Published: September 2024

Previously, we described the mechanisms of development of autoimmune encephalomyelitis (EAE) in 3-month-old C57BL/6, Th, and 2D2 mice. The faster and more profound spontaneous development of EAE with the achievement of deeper pathology occurs in hybrid 2D2/Th mice. Here, the cellular and immunological analysis of EAE development in 2D2/Th mice was carried out. In Th, 2D2, and 2D2/Th mice, the development of EAE is associated with a change in the differentiation profile of hemopoietic bone marrow stem cells, which, in 2D2/Th, differs significantly from 2D2 and Th mice. Hybrid 2D2/Th mice demonstrate a significant difference in these changes in all strains of mice, leading to the production of antibodies with catalytic activities, known as abzymes, against self-antigens: myelin oligodendrocyte glycoprotein (MOG), DNA, myelin basic protein (MBP), and five histones (H1–H4) hydrolyze these antigens. There is also the proliferation of B and T lymphocytes in different organs (blood, bone marrow, thymus, spleen, lymph nodes). The patterns of changes in the concentration of antibodies and the relative activity of abzymes during the spontaneous development of EAE in the hydrolysis of these immunogens are significantly or radically different for the three lines of mice: Th, 2D2, and 2D2/Th. Several factors may play an essential role in the acceleration of EAE in 2D2/Th mice. The treatment of mice with MOG accelerates the development of EAE pathology. In the initial period of EAE development, the concentration of anti-MOG antibodies in 2D2/Th is significantly higher than in Th (29.1-fold) and 2D2 (11.7-fold). As shown earlier, antibodies with DNase activity penetrate cellular and nuclear membranes and activate cell apoptosis, stimulating autoimmune processes. In the initial period of EAE development, the concentration of anti-DNA antibodies in 2D2/Th hybrids is higher than in Th (4.6-fold) and 2D2 (25.7-fold); only 2D2/Th mice exhibited a very strong 10.6-fold increase in the DNase activity of IgGs during the development of EAE. Free histones in the blood are cytotoxic and stimulate the development of autoimmune diseases. Only in 2D2/Th mice, during different periods of EAE development, was a sharp increase in the anti-antibody activity in the hydrolysis of some histones observed.
Exploring the Potential Effects of Cryopreservation on the Biological Characteristics and Cardiomyogenic Differentiation of Rat Adipose-Derived Mesenchymal Stem Cells
Authors: Farag Ahmed , Ngeun Sai Koung , Kaneda Masahiro , Aboubakr Mohamed , Elhaieg Asmaa , Hendawy Hanan , Tanaka Ryou
Published: September 2024

Cryopreservation is essential for the broad clinical application of mesenchymal stem cells (MSCs), yet its impact on their cellular characteristics and cardiomyogenic differentiation potential remains a critical concern in translational medicine. This study aimed to evaluate the effects of cryopreservation on the biological properties and cardiomyogenic capacity of rat adipose-derived MSCs (AD-MSCs). We examined their cellular morphology, surface marker expression (CD29, CD90, CD45), trilineage differentiation potential (adipogenic, osteogenic, chondrogenic), and gene expression profiles for the pluripotency marker REX1 and immunomodulatory markers TGFβ1 and IL-6. After inducing cardiomyocyte differentiation, we assessed cardiac-specific gene expressions (Troponin I, MEF2c, GSK-3β) using quantitative RT-qPCR, along with live/dead cell staining and immunofluorescence for cardiac-specific proteins (Troponin T, α-actinin, Myosin Heavy Chain). Cryopreserved AD-MSCs preserved their morphology, surface markers, and differentiation potential, but exhibited a reduced expression of REX1, TGFβ1, and IL-6. Additionally, cryopreservation diminished cardiomyogenic differentiation, as indicated by the lower levels of Troponin I, MEF2c, and GSK-3β seen compared to non-cryopreserved cells. Despite this, high cell viability (>90%) and maintained cardiac protein expression were observed post-cryopreservation. These findings highlight the necessity of optimizing cryopreservation protocols to ensure the full therapeutic potential of AD-MSCs, particularly in applications related to cardiac regenerative medicine.
The Genome-Wide Identification of the Dihydroflavonol 4-Reductase (DFR) Gene Family and Its Expression Analysis in Different Fruit Coloring Stages of Strawberry
Authors: Chen Li-Zhen , Tian Xue-Chun , Feng Yong-Qing , Qiao Hui-Lan , Wu Ai-Yuan , Li Xin , Hou Ying-Jun , Ma Zong-Huan
Published: September 2024

Dihydroflavonol 4-reductase (DFR) significantly influences the modification of flower color. To explore the role of DFR in the synthesis of strawberry anthocyanins, in this study, we downloaded the CDS sequences of the DFR gene family from the Arabidopsis genome database TAIR; the DFR family of forest strawberry was compared; then, a functional domain screen was performed using NCBI; the selected strawberry DFR genes were analyzed; and the expression characteristics of the family members were studied by qRT-PCR. The results showed that there are 57 members of the DFR gene family in strawberry, which are mainly expressed in the cytoplasm and chloroplast; most of them are hydrophilic proteins; and the secondary structure of the protein is mainly composed of α-helices and random coils. The analysis revealed that FvDFR genes mostly contain light, hormone, abiotic stress, and meristem response elements. From the results of the qRT-PCR analysis, the relative expression of each member of the FvDFR gene was significantly different, which was expressed throughout the process of fruit coloring. Most genes had the highest expression levels in the full coloring stage (S4). The expression of FvDFR30, FvDFR54, and FvDFR56 during the S4 period was 8, 2.4, and 2.4 times higher than during the S1 period, indicating that the DFR gene plays a key role in regulating the fruit coloration of strawberry. In the strawberry genome, 57 members of the strawberry DFR gene family were identified. The higher the DFR gene expression, the higher the anthocyanin content, and the DFR gene may be the key gene in anthocyanin synthesis. Collectively, the DFR gene is closely related to fruit coloring, which lays a foundation for further exploring the function of the DFR gene family.
Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer’s Disease
Authors: Volloch Vladimir , Rits-Volloch Sophia
Published: September 2024

The present study analyzes two potential therapeutic approaches for Alzheimer’s disease (AD). One is the suppression of the neuronal integrated stress response (ISR). Another is the targeted degradation of intraneuronal amyloid-beta (iAβ) via the activation of BACE1 (Beta-site Aβ-protein-precursor Cleaving Enzyme) and/or BACE2. Both approaches are rational. Both are promising. Both have substantial intrinsic limitations. However, when combined in a carefully orchestrated manner into a composite therapy they display a prototypical synergy and constitute the apparently optimal, potentially most effective therapeutic strategy for AD.
Tracking Varroa Parasitism Using Handheld Infrared Cameras: Is Eusocial Fever the Key?
Authors: Sipos Tamás , Orsi-Gibicsár Szilvia , Schieszl Tamás , Donkó Tamás , Zakk Zsombor , Farkas Sándor , Binder Antal , Keszthelyi Sándor
Published: September 2024

The Varroa destructor is the most significant bee parasite and the greatest threat to bee health all around the world. Due to its hidden lifestyle, detection within the brood cell is only possible through invasive techniques. Enhancing detection methods is essential for advancing research on population dynamics, spread, selection efforts, and control methodologies against the mite. In our study, we employed infrared imaging to measure the thermal differences in parasite and intact Apis mellifera worker broods. Experiments were conducted over two years at the MATE Kaposvár Campus in Hungary involving five beehives in 2022 and five beehives in 2023. A FLIR E5-XT WIFI handheld infrared camera was used to create a heat map of capped brood frames. Our results indicate that the resolution of these cameras is sufficient to provide detailed IR images of a bee colony, making them suitable to detect temperature differences in intact and Varroa parasitized capped brood cells. Mite parasitism causes a time-dependent and sustained temperature increase in developing bee pupae, observable regardless of mite number. Our work demonstrates two different heating patterns: hotspot heating and heating cells that are responsible for the elevated temperature of the Varroa-infested cells as a social fever response by the worker bees. Based on our results, future research combined with AI-based image evaluation software could offer beekeepers and researchers practical and valuable tools for high-throughput, non-invasive Varroa detection in the field.
Evolution of the Fermi Surface of 1T-VSe2 across a Structural Phase Transition
Authors: Yilmaz Turgut , Tong Xiao , Sadowski Jerzy T. , Hwang Sooyeon , Lutterodt Kenneth Evans , Kisslinger Kim , Vescovo Elio
Published: September 2024

Periodic lattice distortion, known as the charge density wave, is generally attributed to electron–phonon coupling. This correlation is expected to induce a pseudogap at the Fermi level in order to gain the required energy for stable lattice distortion. The transition metal dichalcogenide 1T-VSe2 also undergoes such a transition at 110 K. Here, we present detailed angle-resolved photoemission spectroscopy experiments to investigate the electronic structure in 1T-VSe2 across the structural transition. Previously reported warping of the electronic structure and the energy shift of a secondary peak near the Fermi level as the origin of the charge density wave phase are shown to be temperature independent and hence cannot be attributed to the structural transition. Our work reveals new states that were not resolved in previous studies. Earlier results can be explained by the different dispersion natures of these states and temperature-induced broadening. Only the overall size of the Fermi surface is found to change across the structural transition. These observations, quite different from the charge density wave scenario commonly considered for 1T-VSe2 and other transition metal dichalcogenides, bring fresh perspectives toward correctly describing structural transitions. Therefore, these new results can be applied to material families in which the origin of the structural transition has not been resolved.
Annealing Behavior of a Mg-Y-Zn-Al Alloy Processed by Rapidly Solidified Ribbon Consolidation
Authors: Gubicza Jenő , Máthis Kristián , Nagy Péter , Jenei Péter , Hegedűs Zoltán , Farkas Andrea , Vesely Jozef , Inoue Shin-ichi , Drozdenko Daria , Kawamura Yoshihito
Published: September 2024

Mg-Y-Zn-Al alloys processed by the rapidly solidified ribbon consolidation (RSRC) technique are candidate materials for structural applications due to their improved mechanical performance. Their outstanding mechanical strength is attributed to solute-enriched stacking faults (SESFs), which can form cluster-arranged layers (CALs) and cluster-arranged nanoplates (CANaPs) or complete the long-period stacking ordered (LPSO) phase. The thermal stability of these solute arrangements strongly influences mechanical performance at elevated temperatures. In this study, an RSRC-processed Mg—0.9%, Zn—2.05%, Y—0.15% Al (at%) alloy was heated at a rate of 0.666 K/s up to 833 K, a temperature very close to melting point. During annealing, in situ X-ray diffraction (XRD) measurements were performed using synchrotron radiation in order to monitor changes in the structure. These in situ XRD experiments were completed with ex situ electron microscopy investigations before and after annealing. At 753 K and above, the ratio of the matrix lattice constants, c/a, decreased considerably, which was restored during cooling. This decrease in c/a could be attributed to partial melting in the volumes with high solute contents, causing a change in the chemical composition of the remaining solid material. In addition, the XRD intensity of the secondary phase increased at the beginning of cooling and then remained unchanged, which was attributed to a long-range ordering of the solute-enriched phase. Both the matrix grains and the solute-enriched particles were coarsened during the heat treatment, as revealed by electron microscopy.
The Synergistic Effect of Calcained Coal-Series Kaolinite and Limestone on the Hydration of Portland Cement
Authors: Tang Jin , Yu Yue , Bu Yuanqing , Ma Bing , Zhou Hao , Zhou Rong , Wang Jiaqing , Zhang Houhu
Published: September 2024

Limestone calcined clay cement (LC3) presents a promising alternative material due to its reduced CO2 emissions and superior mechanical properties compared to traditional Portland cement (PC). This study investigates the synergistic effect of calcined coal-series kaolinite (CCK) and limestone (LS) on the hydration behavior of cement, specifically focusing on varying mass ratios. The combination of CCK and LS promotes the formation of strätlingite and carboaluminates, which enhances early-age strength development. Additionally, the inclusion of CCK facilitates the formation of carboaluminates during later stages of hydration. After 56 days of hydration, the content of carboaluminates is over 10%wt. This stimulation of secondary hydration products significantly refines the evolution of pore structure, with the harmful large pores gradually transformed into harmless medium pores and gel pores, leading to marked improvements in compressive strength from 7 to 28 days. Replacing 45% PC with CCK and LS at mass ratio of 7 to 2, the compressive strength of blends reaches 47.2 MPa at 28 days. Overall, the synergistic interaction between CCK and LS presents unique opportunities to minimize the CO2 footprint of the cement industry without compromising early and long-term performance.