bluuebunny/crossref_metadata_2025 huggingface dataset:
Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis
Authors: Kathuria Ishita , Prasad Aditi , Sharma Bal Krishan , Aithabathula Ravi Varma , Ofosu-Boateng Malvin , Gyamfi Maxwell A. , Jiang Jianxiong , Park Frank , Singh Udai P. , Singla Bhupesh
Published: November 2024

Clinical and genetic studies strongly support a significant connection between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD) and identify ASCVD as the primary cause of death in NAFLD patients. Understanding the molecular factors and mechanisms regulating these diseases is critical for developing novel therapies that target them simultaneously. Our preliminary immunoblotting experiments demonstrated elevated expression of nidogen 2 (NID2), a basement membrane glycoprotein, in human atherosclerotic vascular tissues and murine steatotic livers. Therefore, we investigated the role of NID2 in regulating hepatosteatosis and atherosclerosis utilizing Western diet-fed Apoe−/− mice with/without NID2 overexpression. Quantitative real-time PCR confirmed increased NID2 mRNA expression in multiple organs (liver, heart, kidney, and adipose) of NID2-overexpressing mice. Male mice with NID2 overexpression exhibited higher liver and epididymal white adipose tissue mass, increased hepatic lipid accumulation, and fibrosis. Additionally, these mice developed larger atherosclerotic lesions in the whole aortas and aortic roots, with increased necrotic core formation. Mechanistic studies showed reduced AMPK activation in the livers of NID2-overexpressing mice compared with controls, without any effects on hepatic inflammation. In conclusion, these findings suggest that NID2 plays a deleterious role in both hepatosteatosis and atherosclerosis, making it a potential therapeutic target for these conditions.
The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis
Authors: Tournezy Jeflie , Léger Claire , Klonjkowski Bernard , Gonzalez-Dunia Daniel , Szelechowski Marion , Garenne André , Mathis Stéphane , Chevallier Stéphanie , Le Masson Gwendal
Published: November 2024

In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model. We first tested in vitro the effect of the X-derived peptide (PX3) on motoneurons primary cultures of SOD1G93A mice. The total intracellular adenosine triphosphate (ATP) content was measured after incubation of the peptide. We next tested in vivo the intramuscular injection of X protein using a canine viral vector (CAV2-X) and PX3 intranasal administrations in SOD1G93A mice. Disease onset and progression were assessed through rotarod performance, functional motor unit analysis via electrophysiology, and motor neuron survival by immunohistochemistry. The results showed that in vitro PX3 restored the ATP level in SOD1G93A motor neurons. In vivo, treated mice demonstrated better motor performance, preserved motor units, and higher motor neuron survival. Although life expectancy was not extended in this severe mouse model of motor neuron degeneration, the present findings clearly demonstrate the neuroprotective potential of X protein in a model of ALS. We are convinced that further studies may improve the therapeutic impact of X protein with optimized administration methods.
Genome-Wide Identification and Expression Analysis of ACA/ECAs in Capsicum annuum L.
Authors: Qian Yuxuan , Tong Jing , Liu Ning , Wang Baoju , Wu Zhanhui
Published: November 2024

Pepper (Capsicum annuum L.) is a popular vegetable in people’s daily lives. During pepper growth, calcium (Ca) is an essential macronutrient, and calcium-transporting ATPase (ACA/ECA) is a vital protein for calcium transport. However, reports on the ACA/ECA gene family in the pepper genome are lacking. Hence, we used various bioinformatics methods to identify the ACA/ECA gene family in pepper. We identified eleven CaACA/ECA-family genes in pepper. The chromosomal distribution, phylogenetic evolution, characteristics, gene collinearity, gene and protein structures, cis-acting elements, and specific expression patterns of CaACA/ECAs were analyzed, revealing evolutionary relationships and correlations between CaACA/ECAs and other species (Arabidopsis, rice, and tomato). The experimental results indicate that CaACA/ECAs are stable and hydrophobic proteins, with each of the eleven CaACA/ECA proteins containing all ten motifs. Eleven CaACA/ECA genes are unevenly distributed on the eight chromosomes, and they substantially differ in the number of exons. We found a close correlation between the ACA/ECAs of pepper, Arabidopsis, and tomato. The CaACA/ECA genes contain various plant-hormone-, growth-, and stress-related cis-acting elements. The qRT-PCR results indicate that the expression levels of the eleven CaACA/ECAs exhibit differential temporal expression patterns under various exogenous Ca2+ concentrations. These results provide a theoretical basis for further studying the function of the pepper ACA/ECA gene family and valuable information for identifying and screening genes for pepper stress tolerance breeding.
Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology
Authors: DeVaughn Hunter , Rich Haydn E. , Shadid Anthony , Vaidya Priyanka K. , Doursout Marie-Francoise , Shivshankar Pooja
Published: November 2024

Originally discovered in the 1890s, the complement system has traditionally been viewed as a “compliment” to the body’s innate and adaptive immune response. However, emerging data have shown that the complement system is a much more complex mechanism within the body involved in regulating inflammation, gene transcription, attraction of macrophages, and many more processes. Sustained complement activation contributes to autoimmunity and chronic inflammation. Pulmonary hypertension is a disease with a poor prognosis and an average life expectancy of 2–3 years that leads to vascular remodeling of the pulmonary arteries; the pulmonary arteries are essential to host homeostasis, as they divert deoxygenated blood from the right ventricle of the heart to the lungs for gas exchange. This review focuses on direct links between the complement system’s involvement in pulmonary hypertension, along with autoimmune conditions, and the reliance on the complement system for vascular remodeling processes of the pulmonary artery. Furthermore, circadian rhythmicity is highlighted as the disrupted homeostatic mechanism in the inflammatory consequences in the vascular remodeling within the pulmonary arteries, which could potentially open new therapeutic cues. The current treatment options for pulmonary hypertension are discussed with clinical trials using complement inhibitors and potential therapeutic targets that impact immune cell functions and complement activation, which could alleviate symptoms and block the progression of the disease. Further research on complement’s involvement in interstitial lung diseases and pulmonary hypertension could prove beneficial for our understanding of these various diseases and potential treatment options to prevent vascular remodeling of the pulmonary arteries.
Quality Characteristics of Sustainable High-Performance Concrete Formulated from Binary, Ternary, and Quaternary Supplementary Cementitious Materials Under Various Curing Conditions
Authors: Khan Mohammad Iqbal , Abbas Yassir M. , Fares Galal
Published: November 2024

The formulation of binary, ternary, and quaternary supplementary cementitious materials (SCMs) on an optimized silica fume amount using fly ash, ultrafine (MQ), and limestone powders (LS) is the most sustainable approach to recycling these types of solid wastes for durable concrete. The optimum replacement level of 10% silica fume was blended with different replacement levels of 5, 8, 10, and 15% MQ to formulate different ternary mixes to evaluate the filling effect of MQ. Different ternary mixes containing 10% silica fume and 5, 10, and 15% LS were also produced to examine the effectiveness of both ternary mixtures with either MQ or LS. The quaternary mixtures with 10% silica fume optimized with 20% fly ash and 10% MQ or 10% LS were evaluated for compressive strength, chloride permeability, and porosity. The MQ showed the best filling effect compared to LS. The hot curing conditions significantly enhanced the performance of ternary and quaternary mixtures. Two effects of fillers were observed: the diluting effect brought on by replacement levels and the enhanced filling effect. At early curing, the strength loss resulting from the high replacement level was around 39%; however, this drop could be minimized to approximately 7% under hot curing conditions. It has been demonstrated that the binary, ternary, and quaternary systems offer the best solution to the environmental and durability issues caused by cement. The economic analysis highlights that optimized HPC mixtures with SCMs and fillers, particularly the quaternary mix, achieve superior cost-efficiency and mechanical performance, demonstrating their potential for sustainable and high-performance engineering applications.
Influence of Initial Yield Strength Weighting on Residual Stresses in Quenched Cylinders Using Finite Element Analysis
Authors: Li Junpeng , Xu Yingqiang , Liu Youwei
Published: November 2024

Using the quenching process to create a specific residual stress distribution in steel parts is a key method for improving their strength. Although finite element simulation can overcome the time-consuming and labor-intensive limitations of experimental measurements, accurately predicting the residual stress distribution in quenched steel parts remains a challenge for researchers and manufacturers. The initial yield strength weighting scheme used in finite element simulations has a significant impact on the results. To investigate the influence of initial yield strength weighting on the residual stress distribution in quenched steel cylinders, finite element models with different yield strength weightings have been developed. The results show that the large hardness difference between austenite and martensite can cause significant deviations between the residual stress predicted using linear weighting and the experimental results. The linear weighting scheme commonly used by researchers overestimates the yield strength of the austenite phase in the mixed-phase material during cooling, leading to an overestimation of residual stress. Employing nonlinear yield strength weightings, such as Leblond weighting, can significantly improve the computational accuracy of finite element models, yielding more reliable and consistent predictions. This improved accuracy in predicting residual stress using finite element simulation offers a powerful tool for optimizing the quenching process.
Reduced Graphene Oxide Reinforces Boron Carbide with High-Pressure and High-Temperature Sintering
Authors: Wang Xiaonan , Wang Dianzhen , Rong Kaixuan , Tao Qiang , Zhu Pinwen
Published: November 2024

Introducing a second phase has been an effective way to solve the brittleness of boron carbide (B4C) for its application. Though reduced graphene oxide (rGO) is an ideal candidate for reinforcing the B4C duo’s two-dimensional structure and excellent mechanical properties, the toughness is less than 6 MPa·m1/2, or the hardness is lower than 30 GPa in B4C–graphene composites. A barrier to enhancing toughness is the weak interface strength between rGO and B4C, which limits the bridging and pull-out toughening effects of rGO. In this work, internal stress was introduced using a high-pressure and high-temperature (HPHT) method with B4C–rGO composites. The optimal hardness and toughness values for the B4C-2 vol% rGO composite reached 30.1 GPa and 8.6 MPa·m1/2, respectively. The improvement in toughness was 4 times higher than that of pure B4C. The internal stress in the composite increased gradually from 2.3 GPa to 3.3 GPa with an increase in rGO content from 1 vol% to 3 vol%. Crack deflection, bridging, and rGO pull-out are responsible for the improvement in toughness. Moreover, the high internal stress contributed to the formation of good interface strength by embedding rGO into the B4C matrix particles, which further enhanced the dissipation of the crack energy during the pull-out process and led to high toughness. This work provides new insights into synthesizing high-toughness B4C matrix composites.
Experimental and Numerical Analysis of the Quasi-Static and Dynamic Behavior of Silicate Materials
Authors: Jankowiak Tomasz , Ossowski Jakub Rafał , Rusinek Alexis , Bahi Slim
Published: November 2024

This study investigated both the static and dynamic behavior of silicate materials through a series of experimental and numerical tests. Compression tests were conducted on cubic samples, three-point bending tests on beams, and perforation tests on silicate plates. In the compression tests, stress–strain curves were generated, enabling the calibration of the Concrete Damaged Plasticity (CDP) model for silicate materials. The tensile strength of the silicate was assessed using three-point bending tests, while dynamic perforation tests determined the impact resistance of silicate when subjected to a rigid projectile. The perforation tests provided insight into the failure mechanisms of silicate plates under projectile impact at velocities approaching the ballistic limit. Additionally, the numerical simulations for all the experimental tests were performed using the Abaqus software in order to validate the accuracy of the material behavior model and confirm the appropriateness of the calibrated parameters for the chosen model. The results showed a strong qualitative and quantitative correlation with the experimental data, demonstrating the robustness of the adopted approach.
Characterization of Myrrh Extract Effect on Polylactide and Polypropylene Melt Spun Multifilament Yarn Structure and Properties
Authors: Bolskis Evaldas , Griškonis Egidijus , Marksa Mindaugas , Ragelienė Lina , Adomavičiūtė Erika
Published: November 2024

Myrrh has unique medicinal properties: it is an anti-inflammatory, antifungal, and antibacterial material. The aim of this study was to assess the influence of ethanolic myrrh extract on the production and properties of modified PP and PLA melt spun yarns. In this work, multifilament yarns of polylactide (PLA) and polypropylene (PP) containing 10 wt% myrrh resin at different melt-spinning drawing ratios (DRs) were prepared. The results of scanning electron microscopy revealed that the multifilament yarns from polymers covered by myrrh resin extract had a smooth surface without cracks or visible myrrh derivatives. The influence of myrrh resin on the mechanical properties of PP and PLA multifilament yarns was analyzed, and it was found that the presence of myrrh (PP/M, PLA/M) increased tenacity (cN/tex) and decreased the tensile strain (%) of melt spun yarns obtained at different draw ratios (DRs). During optical analysis, it was found that the absorbance of yarns increased in the entire UV region of the spectra, which was most likely determined by the presence of myrrh. The degree of crystallinity and the wetting angle of PP/M and PLA/M multifilament yarns increased compared with the pure PLA and PP multifilament yarns. This study concludes that the presence of myrrh derivatives influences PLA yarns degradation rate and antibacterial effects against Gram-positive bacteria.
Preparation of Hot-Pressed Wheat Straw Board by Self-Adhesive Process: Effects of Raw Material Sizes and Acid/Alkali Pretreatment
Authors: Wang Jianing , Feng Ziyue , Zuo Jiachen , Fan Qinzhen , Zhang Libo
Published: November 2024

The development of wheat straw boards utilizing intrinsic bonding mechanisms not only facilitates the high-value utilization of agricultural solid waste but also diminishes the reliance on synthetic adhesives. In this study, using wheat straw as the primary substrate, we investigated the effects of mechanical smashing combined with pretreatment using inorganic acids or alkalis on the properties of hot-pressed boards, as well as the relationship between the properties of hot-pressed boards and the physical properties and chemical composition of wheat straw raw materials. These selective pretreatments effectively degraded lignin, hemicellulose, and other components, thereby promoting fiber reorientation and resulting in a denser microstructure with improved self-bonding capabilities. The optimal board was fabricated with a granularity of 0.3 mm and underwent alkali pretreatment, achieving a tensile strength of 11.564 MPa, an internal bonding strength of 0.556 MPa, and bending strength and modulus of 24.306 MPa and 2.766 GPa, respectively. These findings have significant implications for advancing manufacturing processes and conceptualizing binder-free boards derived from agricultural residues.
The Effect of a Zeolite Addition to Modified Bitumen on the Properties of Stone Matrix Asphalt Lärmarmer Mixtures Produced as Warm Mix Asphalt
Authors: Wasilewska Marta , Pacholak Roman , Gierasimiuk Pawel , Gardziejczyk Wladyslaw , Woszuk Agnieszka , Bichajlo Leslaw , Siwowski Tomasz
Published: November 2024

This paper presents the properties of an SMA LA (stone matrix asphalt Lärmarmer) mixture based on the polymer-modified binder PMB 45/80-55, formed by the addition of zeolites (synthetic zeolite type Na-P1 and natural zeolite—clinoptilolite). The compositions of the SMA 11, SMA 8 LA and SMA 11 LA mixtures based on modified bitumen with PMB 45/80-55 (reference mixture) or PMB 45/80-55 with Na-P1 or clinoptilolite were determined. Their resistance to permanent deformation, water sensitivity, water permeability and susceptibility to changes in texture and skid resistance during the period of use were verified. Adding zeolites reduced the production temperature by as much as 15 °C for the SMA 11 LA mixtures and 20 °C for SMA 8 LA. The addition of zeolites did not significantly affect the resistance to permanent deformation, the water permeability or the mass loss. The mixtures with clinoptilolite were resistant to the harmful effects of water, while the mixtures with Na-P1 proved more sensitive to water. Water permeability tests showed a higher permeability for SMA 11 LA compared to SMA 8 LA due to the higher nominal aggregate size. The Cantabro test showed greater particle loss for SMA 11 LA than for SMA 8 LA. A skid resistance and macrotexture analysis indicated that the SMA LA layers required special maintenance on the road due to the clogging of pores in the mix structure.
Quantitative Seismic Damage Assessment of Resilient Concrete Columns Using Drift Ratio-Based Fractal Dimension
Authors: Son Bunka , Li Ganggang , Luo Zhiwei , Sun Yuping
Published: November 2024

The objective of this paper is to develop assessment models to quantitatively evaluate the seismic damage caused to resilient concrete columns intended for buildings located in strong-earthquake-prone regions such as Japan and China. The proposed damage assessment models are based on the fractal analysis of crack patterns on the surface of damaged concrete columns and expressed in the form of a fractal dimension (FD) versus transient drift ratio relationship. To calibrate the proposed damage assessment models, a total of eighty images of crack patterns for eight concrete columns were utilized. All the columns were reinforced by weakly bonded ultra-high-strength (WBUHS) rebars and tested under reversed cyclic loading. The experimental variables covered the shear span ratio of the column, the concrete strength, the axial load ratio, and the amount of steel in the WBUHS rebars. A box-counting algorithm was adopted to calculate or derive the FD of the crack pattern corresponding to each transient drift ratio. The test results reveal that the FD is an efficient image-based quantitative indicator of seismic damage degree for resilient concrete columns and correlates strongly with the transient drift ratio and is subjected to the influence of the shear span ratio. The influence of the other experimental variables on the derived FDs is, if any, little. Based on the test results, a linear equation was developed to define the relationships between the FD and transient drift ratio, and a multi-linear equation was formulated to relate the transient drift ratio to the residual drift ratio, an important index adopted in current design guidelines to measure the repairability of damaged concrete structures. To further verify the efficiency of the drift ratio-based FD in seismic damage assessment, the correlation between the FD and relative stiffness loss (RSL), an indicator used to measure the overall damage degree of concrete structures, was also examined. The driven FD exhibited very strong correlation with RSL, and an empirical equation was developed to reliably assess the overall seismic damage degree of resilient concrete columns with an FD.
Design of Spurious Dynamic Inverter-Based Level Shifter with Error Tolerance for Robotic Arm Controller
Authors: Vijayakumar S. , Poreddy Lachi Reddy , Basha Mohammed Mahaboob , Gopi Karnam , Gundala Srinivasulu , Syed Javed
Published: November 2024

In robotic arm controllers, the ability to shift signal levels is crucial for interfacing between different voltage domains in a processor. The level shifter (LS) has been used to convert signals operating near threshold voltage to signals operating well above the threshold voltage. Researchers have developed current mirror-based LSs to employ current mirrors, which duplicate the current from one transistor and accurately replicate it in another, ensuring precise current matching. In this research, a dynamic inverter-based level shifter (DIBLS) with an error correction circuit is implemented. One of the main issues addressed by DIBLS is the problem of current disagreement. Current disagreement arises when multiple circuit components attempt to draw current from a common source, which leads to operational problems. Furthermore, DIBLS includes a feedback inverter controlled by the output node; this feedback inverter likely plays a pivotal role in controlling and stabilizing the output voltage of operation of the LS. The results demonstrate that DIBLS offers notable advantages on increased operational speed. This speed improvement has been achieved by circumventing the threshold voltage drop associated with the feedback of the inverter and by ensuring complete output swing, addressing stability issues. Voltage shifting between 0.3 V and 1.2 V at 1 MHz having power consumption is 16.57 nW, delay 0.22 ns, and energy per transition 32.25 fJ. The entire process is executed in 45 nm in CMOS technology.
Suspended Slot Membrane Waveguide Based on Germanium-on-Silicon-on-Insulator at λ = 4.23 µm for CO2 Monitoring
Authors: Butt Muhammad A. , Piramidowicz Ryszard
Published: November 2024

In this work, we propose a novel suspended slot membrane waveguide (SSMW) utilizing a germanium-on-silicon-on-insulator (Ge-on-SOI) platform for carbon dioxide (CO2) gas-sensing applications. The design and analysis focus on the absorption line of CO2 in the mid-infrared region, specifically at a wavelength of 4.23 µm. The waveguide geometry has been precisely optimized to achieve a high evanescent field ratio (EFR) and minimize waveguide propagation losses. These optimizations significantly enhance the sensitivity of the waveguide, making it highly effective for evanescent field absorption-based gas sensing. Our optimized waveguide geometry demonstrates a notable EFR of 0.86, with a low propagation loss of just 1.07 dB/cm, and achieves a sensitivity as high as ~1.12 × 10−4 ppm−1 for SSMW lengths as short as 0.9 cm.
Prevalence, Risk Factors, and Clinical Management of Disease-Related Malnutrition in Hospitalized Patients: A Descriptive Analysis Using GLIM and SGA Criteria
Authors: Reyes Laura Mola , García-Moreno Rosa M. , López-Plaza Bricia , Milla Samara Palma
Published: November 2024

Objectives: This study aimed to assess the prevalence and risk factors associated with disease-related malnutrition (DRM) in hospitalized patients using the Subjective Global Assessment (SGA) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Additionally, we sought to identify key determinants of moderate and severe malnutrition. Methods: A retrospective analysis was conducted on 1036 adult patients hospitalized in a tertiary care hospital between August 2019 and November 2020. Nutritional status was evaluated using both the SGA and GLIM criteria. Data on demographic characteristics, comorbidities, dietary intake, and gastrointestinal symptoms were collected. Logistic regression models were employed to identify risk factors for DRM, and multivariate analysis was used to determine independent predictors. Results: The prevalence of DRM was 63.3% according to GLIM and 64.8% according to SGA. Moderate malnutrition was observed in 22.6% of patients, while 40.7% were classified as having severe malnutrition, and severe weight loss was noted in 34.5% of the subjects. The key risk factors for DRM included male sex (OR 1.67, p < 0.0001), non-oncological gastrointestinal conditions (OR 1.48, p = 0.041), infectious diseases (OR 1.66, p = 0.007), inadequate ingestion (OR 5.13, p < 0.0001), and the presence of gastrointestinal symptoms (OR 3.06, p < 0.0001). Individualized diets were found to have a protective effect, while central parenteral nutrition significantly reduced the risk of severe DRM (OR 0.610, p = 0.014). In the final adjusted model, sex (p < 0.0001), ingestion (p < 0.0001), and gastrointestinal symptoms (p < 0.0001) emerged as the most significant independent predictors of DRM. Conclusions: The high prevalence of DRM in hospitalized patients emphasizes the importance of routine nutritional screening and personalized interventions. Proactive management of key risk factors such as inadequate intake and gastrointestinal symptoms is crucial to mitigating malnutrition and improving patient outcomes.
Protective Effects of the Food Supplement Flexovital in a Model of Cardiovascular-Kidney-Metabolic Syndrome in Mice
Authors: Carvalho Lucas , Tydén Maria , Shimari Miho , Zhuge Zhengbing , Schiffer Tomas , de Oliveira Monteiro Matheus , Lundberg Jon , Weitzberg Eddie , Andersson Daniel , Fellström Bengt , Carlström Mattias
Published: November 2024

Background/Objectives: The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome is increasing rapidly, and cardiovascular complications pose significant risks in individuals with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronic Western diet (WD) feeding. Methods: C57BL/6J mice underwent UNX and were fed a WD high in salt, sugar, and fat for 12 weeks, compared to sham-operated mice on standard chow. One group of UNX+WD mice received Flexovital (FLX), a food additive containing extracts of Rhodiola rosea and beetroot, and the amino acids L-arginine and L-citrulline. CKM parameters were assessed both in vivo and ex vivo alongside histological and biochemical analyses. Results: The UNX+WD mice showed an increase in body fat mass, the fat/lean mass ratio, and adipocyte area, of which most were significantly reduced by FLX. Elevated fasting glucose levels were also reduced by FLX, which tended towards improving glucose clearance. Elevated arterial blood pressure and endothelial dysfunction in UNX+WD mice were significantly reduced by FLX. FLX improved GFR and reduced glomerular and tubular injuries in UNX+WD mice. Additionally, FLX increased the P/O ratios of oxidative phosphorylation in the isolated renal mitochondria of UNX+WD mice. Conclusions: In this model of CKM syndrome, FLX effectively prevented the onset and progression of CKM dysfunctions induced by UNX+WD, as well as the associated organ injuries. These promising results highlight the need for validation in upcoming human trials.
The Anti-Metastatic Potential of Aronia Leaf Extracts on Colon Cancer Cells
Authors: Owczarek Katarzyna , Caban Miłosz , Sosnowska Dorota , Kajszczak Dominika , Lewandowska Urszula
Published: November 2024

Background/Objectives: Numerous studies have demonstrated the health benefits of polyphenols found in aronia fruits; however, little is known about how aronia leaf polyphenols impact colorectal cancer (CRC). This study aimed to evaluate the in vitro anti-metastatic and anti-invasive activity of crude aronia leaf extract (ACE) and purified phenolic-rich aronia leaf extract (APE) against two CRC cell lines (SW-480 and HT-29). Methods: Migration and invasion potential of ACE and APE were evaluated. Moreover, ELISA and gelatin zymography were performed to detect translational and activity changes in CRC cells after aronia extracts treatment. Results: We found that a 100 µg/mL concentration of ACE and APE almost entirely downregulated the migration and invasion of SW-480 cells, showing greater effectiveness than HT-29 cells. The observed inhibition was concentration-dependent and statistically significant. Additionally, extracts reduced the product of MMP-2 and MMP-9 gene expression at the protein level and simultaneously inhibited the activity of both MMPs. An APE at 300 µg/mL for SW-480 and 600 µg/mL for HT-29 resulted in a notable reduction in MMP-2 protein synthesis by 72% and 50%, respectively. In contrast, MMP-9 protein synthesis decreased by 48% and 59% in HT-29 cells treated with 300 µg/mL and 600 µg/mL of ACE, respectively. The levels of gelatinase activity were similar for both CRC lines, and the APE tested at a concentration of 300 µg/mL reached almost the IC50 value after 48 h of incubation. Conclusions: Based on the presented results, we provided an experimental foundation for future in vitro and in vivo studies on the potential effects and activities of aronia leaves.
The Prevention of Maternal Phenylketonuria (PKU) Syndrome: The Development and Evaluation of a Specific Training Program
Authors: Rohde Carmen , Thiele Alena Gerlinde , Tomm Anne , Lier Dinah , Eschrich Kathrin , Baerwald Christoph , Beblo Skadi
Published: November 2024

Background: Maternal phenylketonuria (PKU) syndrome, leading to severe psychomotor retardation, microcephaly, cardiac defects and undergrowth, affects the unborn children of mothers with PKU with insufficient metabolic control during pregnancy. To improve long-term outcomes, a specific prevention program was developed. Methods: We designed a group training program for young women with PKU (>14 years) and their partners. Knowledge regarding PKU therapy and pregnancy was evaluated by a specifically developed multiple-choice questionnaire. In addition, scores of anxiety and depression were evaluated. Results: Patients (n = 20) and their partners (n = 13) significantly improved their knowledge after participation (correct answers: patients—86% vs. 90%, p = 0.003; partners—78% vs. 89%, p = 0.012). Females significantly improved their knowledge about diet (90% vs. 100%, p = 0.035) and metabolism (91% vs. 100%, p = 0.016), but not concerning gynecological topics. Patients’ median depression scores were within the normative range, with a slight decrease over time (6 points vs. 4 points, p = 0.836). Patients’ anxiety score remained stable over time (5.5 vs. 5, p = 0.247). Of trained mothers with PKU, four pregnancies with ideal metabolic control and healthy offspring could be observed. Conclusion: We suggest the inclusion of specific training programs in the standard care of female young adults with PKU, including for their partners.
Determinants of Malnourishment in the Institutionalized Older Population: The FRAGILESS Study
Authors: Leira Julia , Maseda Ana , López-López Rocío , Lorenzo-López Laura , Cibeira Nuria , Lodeiro-Fernández Leire , Millán-Calenti José C.
Published: November 2024

Background/Objectives: Malnutrition is a very common condition among older people and strongly affects their quality of life. The current literature relates the presence of nutritional deficiencies to several health-related factors that usually emerge at advanced stages of life. This study aimed to assess the associations between malnutrition and its determinants in a group of institutionalized older people via the Mini Nutritional Assessment–Short Form (MNA-SF) and the full MNA. Methods: The MNA-SF was compared with the full MNA to evaluate the nutritional status of 207 older people. A multinomial logistic regression analysis was performed. Results: The data revealed that institutionalized older people with cognitive impairment, frailty syndrome, dysphagia, a low BMI, a high duration of institutionalization, and a low educational level are more likely to be malnourished or at risk of malnutrition. Conclusions: The results reveal that the MNA or MNA-SF may not identify common determinants of malnutrition or nutritional risk. The identified determinants depend on the test. Therefore, the data obtained determine the need to use adequate nutritional screening tools to control the presence of malnutrition. Nutritional screening is essential to decrease public costs, hospitalizations, rates of disability, dependence, morbidity, and even mortality among institutionalized older people.
The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation
Authors: Jang Yumi , Kim Choon Young
Published: November 2024

Natural forms of vitamin E include four tocopherols and four tocotrienols (α, β, γ, and δ), which are essential as lipophilic antioxidants. Among these eight isoforms, α-tocopherol (αT), the predominant form of vitamin E found in tissues, has traditionally received the most attention in disease prevention research due to its robust antioxidant activity. However, recent studies suggest that other forms of vitamin E exhibit distinct and potentially more potent beneficial activities in disease prevention and treatment. These non-αT forms of vitamin E are metabolized in vivo, producing various metabolites, including 13′-carboxychromanol, though their biological roles remain largely unknown. Notably, sphingolipids, known for their significant roles in cancer biology, may be involved in the anticancer effects of vitamin E through the modulation of sphingolipid metabolism. This review focuses on the diverse biological activities of different vitamin E forms and their metabolites, particularly their anticancer effects, while highlighting the underlying mechanisms, including their novel impact on regulating sphingolipid pathways. By elucidating these interactions, we aim to provide a deeper understanding on the multifaceted roles of vitamin E in cancer prevention and therapy.
High-Carbohydrate Energy Intake During a Round of Golf-Maintained Blood Glucose Levels, Inhibited Energy Deficiencies, and Prevented Fatigue: A Randomized, Double-Blind, Parallel Group Comparison Study
Authors: Nagashima Yosuke , Ehara Kiyohiro , Ehara Yoshitomo , Mitsume Ayana , Uchikoba Yuhei , Mineo Shigeru
Published: November 2024

Objectives: This study primarily aimed to examine the optimal amount of carbohydrates in the effects of high-isomaltulose and high-sucrose ingestion compared with low-sucrose ingestion on blood glucose levels. The secondary objective was to assess the changes in blood glucose levels that may impact golf-related performance. Methods: This study included 29 healthy male competitive golfers playing 18 holes. These participants were randomly assigned to the low-sucrose (LSUC, 30.9 g/h of carbohydrates), high-sucrose (HSUC, 44.2 g/h of carbohydrates), and high-isomaltulose (HISO, 44.5 g/h of carbohydrates) groups. They were required to continuously consume the test food during the round. Assessment items included blood glucose, golf performance, urinary urea nitrogen, subjective ratings (concentration, fatigue, and relaxation), and anxiety ratings. A main effect of the test meal of changes in interstitial glucose concentration was determined. Results: The HSUC had significantly more interstitial glucose than the HISO and LSUC, while the HISO group had a much lower decrease in urine urea nitrogen than the LSUC group. In subjective fatigue, the main effect of the test diet was observed, and the HSUC and HISO showed significantly lower values than the LSUC after 18 h. Conclusions: Compared with low-carbohydrate intake, high-carbohydrate intake during a round of golf-maintained the blood glucose levels and prevented fatigue. Therefore, this study indicates that competitive golfers need a high-carbohydrate intake of approximately 44 g/h for energy intake during a round of golf.
Age and Gender Disparities in the Association of Long-Term Dietary Choline and Choline Compound Intakes with Incident Cognitive Decline in Middle-Aged and Older Chinese Adults: A Prospective Cohort Study
Authors: Jia Xiaofang , Su Chang , Zhang Jiguo , Huang Feifei , Bai Jing , Guan Fangxu , Wei Yanli , Li Li , Liu Yibing , Ji Jingang , Du Wenwen , Ouyang Yifei , Zhang Xiaofan , Zhang Bing , Wang Huijun
Published: November 2024

Background/Objectives: The neuroprotective role of dietary choline during adulthood has not yet been conclusively proven. This study aims to investigate the influence of long-term choline and its constituent intakes on cognitive decline in the Chinese population. Methods: A total of 4502 subjects (≥55 years) with at least two waves of completed data and without cognitive decline at baseline were selected from the China Health and Nutrition Survey 1997–2018. Three consecutive 24 h dietary recalls were performed to collect dietary intake information for choline, phosphatidylcholine (PC), and glycerophosphocholine (GPC) measures. Several items from the Telephone Interview for Cognitive Status (Modified) were employed to perform a cognitive assessment. Cox frailty models were used to estimate hazard ratios (HRs) and 95% CIs. Results: A total of 783 participants developed cognitive decline during 26,080 person-years of follow-up. Cumulative average intakes of choline, PC, and GPC were 188.0, 126.7, and 17.1 mg/d, respectively. In the total population, after full adjustment, subjects in the lower (Q2), medium (Q3), higher (Q4), and highest (Q5) quintiles of dietary choline showed 27.8% (95% CI: 0.584, 0.894), 33.9% (95% CI: 0.522, 0.836), 23.0% (95% CI: 0.599, 0.990), and 29.3% (95% CI: 0.526, 0.949) decreases in the risk of cognitive decline compared to the lowest (Q1), respectively. Similar results were observed in PC but not GPC measures. Both higher choline and PC intakes induced a lower risk of cognitive decline for subjects ≥ 65 years at baseline (Q3 and Q4) and females (Q2–Q5). A marginally significant association of GPC was found for subjects ≥ 65 years (Q5) and males (Q4). Conclusions: These findings identify age and gender disparities relating to the protective associations of dietary choline, PC, and GPC with incident cognitive decline in middle-aged and older Chinese populations.
A Comprehensive Review on Dietary Polysaccharides as Prebiotics, Synbiotics, and Postbiotics in Infant Formula and Their Influences on Gut Microbiota
Authors: Zhang Wenyuan , Zhang Yanli , Zhao Yaqi , Li Liang , Zhang Zhanquan , Hettinga Kasper , Yang Haixia , Deng Jianjun
Published: November 2024

Human milk contains an abundance of nutrients which benefit the development and growth of infants. However, infant formula has to be used when breastfeeding is not possible. The large differences between human milk and infant formula in prebiotics lead to the suboptimal intestinal health of infant formula-fed infants. This functional deficit of infant formula may be overcome through other dietary polysaccharides that have been characterized. The aim of this review was to summarize the potential applications of dietary polysaccharides as prebiotics, synbiotics, and postbiotics in infant formula to better mimic the functionality of human milk prebiotics for infant gut health. Previous studies have demonstrated the influences of dietary polysaccharides on gut microbiota, SCFA production, and immune system development. Compared to prebiotics, synbiotics and postbiotics showed better application potential in shaping the gut microbiota, the prevention of pathogen infections, and the development of the immune system. Moreover, the safety issues for biotics still require more clinical trials with a large-scale population and long time duration, and the generally accepted regulations are important to regulate related products. Pectin polysaccharides has similar impacts to human milk oligosaccharides on gut microbiota and the repairing of a damaged gut barrier, with similar functions also being observed for inulin and β-glucan. Prebiotics as an encapsulation material combined with probiotics and postbiotics showed better potential applications compared to traditional material in infant formula.
Modulation of FOXP3 Gene Expression in OVCAR3 Cells Following Rosmarinic Acid and Doxorubicin Exposure
Authors: Toprak Veysel , Özdemir İlhan , Öztürk Şamil , Yanar Orhan , Kizildemir Yusuf Ziya , Tuncer Mehmet Cudi
Published: November 2024

Background/Objectives: Ovarian cancer has the highest mortality rate in the world. Treatment methods are listed as surgery, chemotherapy, and radiotherapy, depending on the stage of cancer, but developing resistance to chemotherapy increases the need for alternative agents that act on the same pathways. The effects of rosmarinic acid (RA) and doxorubicin (DX) on the activation of FOXP3, an important tumor suppressor gene, in OVCAR3 cells were examined. Materials and Methods: In this study, a human ovarian adenocarcinoma cell line was used. MTT analysis was performed to reveal the result of RA and DX on ovarian cancer cell proliferation. Expression levels of FOXP3 for cell proliferation and Capase-3 for apoptosis were determined by RT-qPCR. The wound healing model was applied to determine cell migration rates. The results were evaluated with one-way ANOVA in an SPSS 20.0 program as p ≤ 0.05. Results: It was determined that RA and DX alone and in combination inhibited the proliferation of OVCAR3 cells in different doses for 24, 48, and 72 h, and caused the cells to die by causing them to undergo apoptosis. Caspase-3 expression increased approximately tenfold in OVCAR3 cells, while FOXP3 expression was upregulated only in RA treatment and was downregulated in DX and RA + DX treatments. Conclusions: According to the results of our study, it was determined that the FOXP3 signaling pathway related to apoptosis, and proliferation was affected by the combination treatment of RA and DX in the OVCAR3 cancer cell line. This shows that RA will gain an important place in cancer treatment with more comprehensive study.
Autism-Linked Mutations in α2δ-1 and α2δ-3 Reduce Protein Membrane Expression but Affect Neither Calcium Channels nor Trans-Synaptic Signaling
Authors: Haddad Sabrin , Hessenberger Manuel , Ablinger Cornelia , Eibl Clarissa , Stanika Ruslan , Campiglio Marta , Obermair Gerald J.
Published: November 2024

Background: α2δ proteins regulate membrane trafficking and biophysical properties of voltage-gated calcium channels. Moreover, they modulate axonal wiring, synapse formation, and trans-synaptic signaling. Several rare missense variants in CACNA2D1 (coding for α2δ-1) and CACNA2D3 (coding for α2δ-3) genes were identified in patients with autism spectrum disorder (ASD). However, the pathogenicity of these variants is not known, and the molecular mechanism by which α2δ proteins may contribute to the pathophysiology of autism is, as of today, not understood. Therefore, in this study we functionally characterized two heterozygous missense variants in α2δ-1 (p.R351T) and α2δ-3 (p.A275T), previously identified in patients with ASD. Methods: Electrophysiological recordings in transfected tsA201 cells were used to study specific channel-dependent functions of mutated α2δ proteins. Membrane expression, presynaptic targeting, and trans-synaptic signaling of mutated α2δ proteins were studied upon expression in murine cultured hippocampal neurons. Results: Homologous expression of both mutated α2δ proteins revealed a strongly reduced membrane expression and synaptic localization compared to the corresponding wild type α2δ proteins. Moreover, the A275T mutation in α2δ-3 resulted in an altered glycosylation pattern upon heterologous expression. However, neither of the mutations compromised the biophysical properties of postsynaptic L-type (CaV1.2 and CaV1.3) and presynaptic P/Q-type (CaV2.1) channels when co-expressed in tsA201 cells. Furthermore, presynaptic expression of p.R351T in the α2δ-1 splice variant lacking exon 23 did not affect trans-synaptic signaling to postsynaptic GABAA receptors. Conclusions: Our data provide evidence that the pathophysiological mechanisms of ASD-causing mutations of α2δ proteins may not involve their classical channel-dependent and trans-synaptic functions. Alternatively, these mutations may induce subtle changes in synapse formation or neuronal network function, highlighting the need for future α2δ protein-linked disease models.
Green Synthesis of Biocompatible Chiral Gold Nanoparticles
Authors: Fan Yuan , Li Na , Wang Jiaolong , Liao Lan , Wei Junchao
Published: November 2024

Chiral gold nanoparticles (Au NPs) have been investigated widely and have shown great potential in biomedical applications, such as biosensing, combating bacterial infections and tissue regeneration. However, some stabilizers and reducing agents for the synthesis of chiral Au NPs can produce toxicity in living organisms. Therefore, it is interesting to design green methods to prepare chiral gold nanoparticles that are nontoxic, environment-friendly, and low-cost. Herein, novel biocompatible chiral Au NPs with a diameter of 54.4 ± 14.9 nm were prepared by the in situ reduction of HAuCl4 with alginates as the green reducing agent and chiral-inducing and stabilizing agent. XPS, TGA, UV-Vis and CD analyses demonstrated that alginate-stabilized chiral Au NPs (ALG-Au NPs) were successfully prepared, while biocompatibility assessment showed that cell viability was 116.0% when the concentration of ALG-Au NPs arrived at 300 μg/mL, which indicated that ALG-AuNPs showed excellent biocompatibility. Furthermore, the ALG-Au NPs can respond to metal ions, such as Ca2+, Cu2+, Mn2+ and so on, implying potential application for biosensing.
Additively Manufactured Carbon Fibre PETG Composites: Effect of Print Parameters on Mechanical Properties
Authors: Economides Andreas L. , Islam Md Niamul , Baxevanakis Konstantinos P.
Published: November 2024

This study investigates the quasi-static and viscoelastic properties of additively manufactured (AM) PETG reinforced with short carbon fibres. Samples were manufactured using different parameters in terms of the infill pattern, porosity, and annealing condition. Tensile and compressive tests were conducted to determine quasi-static properties such as Young’s modulus and toughness, and dynamic mechanical analysis was used under a frequency sweep of 1–100 Hz to describe the viscoelastic behaviour of the composites. The major impacts and responses between the print parameters were quantified using Analyses of Variance (ANOVAs), which revealed the major contributor to each mechanical property. Fractography on the tensile samples using scanning electron microscopy demonstrated fibre pull-out, indicating poor fibre–matrix bonding, but also revealed interfacial bonding between raster lines in the annealed samples. This had a prominent effect on the properties of latitudinal samples where the force applied was perpendicular to the raster lines. Generally, porosity appeared to have the greatest contribution to the variance in the mechanical properties, with the exception of the tensile modulus, where the infill pattern had a more substantial effect. Annealing caused a consistent increase in the tensile modulus of the tested samples, which can be used to support the design and optimisation of AM parts when they are used under specific loading conditions.