bluuebunny/crossref_metadata_2025 huggingface dataset:
Doherty Power Amplifier Design via Differential Combining
Authors: Moreno Rubio Jorge Julian , Noori Abdolhamid
Published: October 2024

This paper introduces a novel differential combiner designed to effectively address parasitic capacitances of transistors used in power amplifier (PA) designs with precise compensation at a specified frequency. The combiner consists of a λ/4 transmission line with an integrated capacitor of value 2COUT at its midpoint, which ensures accurate cancellation of parasitic effects. This design connects the drain pins of two transistors, which are considered identical in this configuration. By eliminating the need for complex parasitic compensation techniques, this method significantly simplifies the design process of Doherty Power Amplifiers (DPAs). Extensive simulations validate the effectiveness of this approach, highlighting its potential as a versatile and straightforward solution for next-generation communication systems.
Real-Time Embedded Control of Vehicle Dynamics Using ESP32: A Discrete Nonlinear Approach
Authors: Guzmán Antonio Navarrete , Lúa Cuauhtémoc Acosta , García-Rodríguez J. A. , Vidrios-Serrano Carlos , Meza-Aguilar Marco A.
Published: October 2024

This article explores the application of the Espressif ESP32 System-On-Chip (SoC) for managing vehicle dynamics through real-time digital proportional–integral (PI-like) control. We present the development of advanced driving assistance algorithms for Active Front Steering (AFS) and Rear Torque Vectoring (RTV) on this cost-effective, commercially available embedded system. Using digital PI-like control algorithms designed for AFS and RTV, the primary ESP32 board receives and processes steering signals, executing a discrete-time control model of the vehicle dynamic to enable dynamic adjustments to steering and torque. To enhance simulation realism, a secondary ESP32 is employed to generate the steering signal, effectively mimicking a steer-by-wire system via its analog output ports. This configuration facilitates the simulation and evaluation of control algorithms in a realistic test environment, ensuring enhanced vehicle dynamic stability and maneuverability under various conditions. Additionally, simulations are conducted using MATLAB 2023a and CarSim 2017.1 to compare the efficacy and benefits of the implementation. Our objective is to establish a platform for evaluating discrete controllers capable of real-time vehicle operation. This methodology accelerates and reduces the cost of improving vehicle system stability and responsiveness, enabling the immediate verification and fine-tuning of control parameters as needed.
Research on Multi-Objective Optimization Methods of Urban Rail Train Automatic Driving Based on NSGA-II
Authors: Chen Xiaoqiang , Meng Jianjun , Xu Ruxun , Li Decang , Yang Haobo
Published: October 2024

In order to improve the control performance of automatic train operation (ATO) in urban rail trains, five typical operating sequences of urban rail trains were studied. Under the condition of meeting the safety and comfort principles of train operation, a train dynamics model was established to achieve the goals of low energy consumption, short running time, and high stopping accuracy in urban rail transit trains. In the process of finding a multi-objective solution to this problem, the Non-dominated Sorting Genetic Algorithm II (NSGA-II) was used with an elite retention strategy, and the optimal Pareto multi-objective solution set was sought. In the process of optimal solution weight assignment, the hierarchical analysis Mahalanobis distance method, which combines subjective and objective analysis, was used. Finally, taking the Beijing Yizhuang subway line as the background design example, the simulation verified the effectiveness and feasibility of the algorithm and obtained high-quality automatic train driving curves under various working conditions. This research has important reference significance for the actual operation of automatic driving in urban rail trains.
Performance and Latency Efficiency Evaluation of Kubernetes Container Network Interfaces for Built-In and Custom Tuned Profiles
Authors: Dakić Vedran , Redžepagić Jasmin , Bašić Matej , Žgrablić Luka
Published: October 2024

In the era of DevOps, developing new toolsets and frameworks that leverage DevOps principles is crucial. This paper demonstrates how Ansible’s powerful automation capabilities can be harnessed to manage the complexity of Kubernetes environments. This paper evaluates efficiency across various CNI (Container Network Interface) plugins by orchestrating performance analysis tools across multiple power profiles. Our performance evaluations across network interfaces with different theoretical bandwidths gave us a comprehensive understanding of CNI performance and overall efficiency, with performance efficiency coming well below expectations. Our research confirms that certain CNIs are better suited for specific use cases, mainly when tuning our environment for smaller or larger network packets and workload types, but also that there are configuration changes we can make to mitigate that. This paper also provides research into how to use performance tuning to optimize the performance and efficiency of our CNI infrastructure, with practical implications for improving the performance of Kubernetes environments in real-world scenarios, particularly in more demanding scenarios such as High-Performance Computing (HPC) and Artificial Intelligence (AI).
Influence of Reaction Conditions on the Yield of Supercritical Multicomponent Thermal Fluids
Authors: Zhang Wei , Qi Zhilin , Tian Jie , Xu Fang , Kong Deyu , Dong Mingda , Yang Shenyao , Yan Wende
Published: October 2024

Supercritical multicomponent thermal fluid (scMCTF) is a novel medium with great potential for heavy oil thermal recovery. The production rate of scMCTF will affect the injection efficiency of thermal fluid, and then affect the development effect of thermal recovery. However, at present, there are few reports on the production rate of each component of scMCTF, and their understanding is not clear. According to the existing production rate data of supercritical water (scH2O) gasification products, based on the generation mechanism of scMCTF, the production rate of thermal fluid generation products under different generation conditions was calculated, and its influencing factors were identified. The results show the following: (1) The factors affecting the production rate of scMCTF generation products can be divided into three categories: reaction raw material factors, reaction condition factors, and catalytic factors. (2) The hydrocarbon number of raw material, reaction temperature, reaction time, and catalyst concentration were positively correlated with the production rate of the product. (3) The concentration of the reaction raw material is negatively correlated with the production rate of the product. The higher the concentration of the raw material is, the lower the concentration of H2O is, and the steam reforming reaction is inhibited, which leads to the decrease in the production rate. (4) The effect of reaction pressure and catalyst load on the product is not significant. (5) The reaction product production rate increased first and then decreased with the ratio of H2O to oil in the raw material emulsion and the ratio of preheated H2O to raw material discharge. (6) The effect of metal salt catalysts is relatively stable, and the catalytic effect of simple metal catalysts is significantly different under the action of different types of accelerators, so it is necessary to study the degree of synergization of different accelerators on the catalytic effect. The results can lay a foundation for the subsequent experimental and theoretical research design.
Resilience of Pinus pinea L. Trees to Drought in Central Chile Based on Tree Radial Growth Methods
Authors: Loewe-Muñoz Verónica , Del Río Rodrigo , Delard Claudia , Cachinero-Vivar Antonio M. , Camarero J. Julio , Navarro-Cerrillo Rafael , Balzarini Mónica
Published: October 2024

The increasing occurrence of dry and hot summers generates chronic water deficits that negatively affect tree radial growth. This phenomenon has been widely studied in natural stands of native species but not in commercial plantations of exotic tree species. In central Chile, where the species is increasingly planted, the dynamics of stone pine (Pinus pinea L.) growth under drought have been little explored. We studied the impact of drought on four stone pine plantations growing in central Chile. We sampled and cross-dated a total of 112 trees from four sites, measured their tree-ring width (RWL) series, and obtained detrended series of ring width indices (RWIs). Then, we calculated three resilience indices during dry years (Rt, resistance; Rc, recovery; and Rs, resilience), and the correlations between the RWI series and seasonal climate variables. We found the lowest growth rate (1.94 mm) in the driest site (Peñuelas). Wet conditions in the previous winter and current spring favored growth. In the wettest site (Pastene), the growth rates were high (4.87 mm) and growth also increased in response to spring thermal amplitude. Overall, fast-growing trees were less resilient than slow-growing trees. Drought reduced stone pine stem growth and affected tree resilience to hydric deficit. At the stand level, growth rates and resistance were driven by winter and spring precipitation. Fast-growing trees were more resistant but showed less capacity to recover after a drought. In general, stone pine showed a high post-drought resilience due to a high recovery after drought events. The fact that we found high resilience in non-native habitats, opens new perspectives for stone pine cropping, revealing that it is possible to explore new areas to establish the species. We conclude that stone pine shows a good acclimation in non-native, seasonally dry environments.
Synthesis of Carbon Nanofibers from Lignin Using Nickel for Supercapacitor Applications
Authors: Nazhipkyzy Meruyert , Maltay Anar B. , Seilkhanov Tulegen M.
Published: October 2024

Carbon fiber is known for being lightweight and adaptable, making it useful for various current and future applications. However, to broaden the use of carbon fibers beyond niche applications, production costs must be lowered. A potential approach to achieving this is by using more affordable raw materials, such as lignin, which is renewable, cost-effective, and widely available compared with the materials commonly used in industry today. This study explores the impact of metal ions on the quality of carbon fiber derived from lignin, focusing on its mechanical and electrochemical properties and morphology. The effect of a specific metal ion (Ni(NO3)2·6H2O) was examined by incorporating it into the spinning solution. The carbonization stage of the fiber was conducted at temperatures of 800, 900, and 1000 °C in an inert atmosphere. Scanning electron microscopy (SEM) analysis showed no defects or damage in any of the fibers. Therefore, it was concluded that moderate concentrations of Ni2+ ions in the fibers do not influence the stabilization or carbonization processes, thus leaving the mechanical properties of the final carbon fiber unchanged. These carbon nanofibers were also tested as a sustainable alternative to the non-renewable materials used in electrodes for energy storage and conversion devices, such as supercapacitors. Electrochemical performance was assessed in a 6 M KOH solution using a two-electrode cell configuration. Galvanostatic charge–discharge tests were performed at different current densities (0.1, 0.25, 0.5, 1.0, and 2.0 A g−1). The specific capacitance of the carbon nanofibers was determined from CVA data at various scan rates: 5, 10, 20, 40, 80, and 160 mV s−1. The results indicated that at 0.1 A g−1, the capacitance reached 108 F g−1, and at a scan rate of 5 mV s−1, it was 91 F g−1. The innovation of this work lies in its use of lignin, a renewable and widely available material, to produce carbon fibers, reducing costs compared with traditional methods. Additionally, the incorporation of nickel ions enhances the electrochemical properties of the fibers for supercapacitor applications without compromising their mechanical performance.
Effects of Taurine and Enzymatic Cottonseed Protein Concentrate Supplementation in Low-Fishmeal Diet on Growth, Liver Antioxidant Capacity, and Intestinal Health of Golden Pompano (Trachinotus ovatus)
Authors: Wang Zhanzhan , Liao Shuling , Huang Zhong , Wang Jun , Wang Yun , Yu Wei , Lin Heizhao , Ma Zhenhua , Cheng Zhenyan , Zhou Chuanpeng
Published: October 2024

This study was conducted to investigate the impacts of the dietary addition of taurine and enzymatic cottonseed protein concentrate (ECPC) in low-fishmeal diet on the growth performance, plasma biochemical indices, hepatic antioxidant capacity, intestinal anti-inflammatory capacity, intestinal microflora, and muscle quality of golden pompano (Trachinotus ovatus). A total of three isonitrogenous diets were given to 225 golden pompanos (5.6 ± 0.14 g). They were randomly divided into nine cages (1.0 m × 1.0 m × 1.5 m; three cages per treatment) with equal stocking numbers of twenty-five fish per cage. The results indicated that the CSM-TC group significantly increased the growth performance of juvenile T. ovatus (p < 0.05). The results indicated that compared with other groups, the addition of 1% ECPC and 0.25% taurine has been found to enhance the WGR (weight gain rate), SGR (specific growth rate), and CF (condition factor). Compared with other groups, the relative expressions of GH, GHR1, GHR2, IGF1, IGF2, and MyoG were significantly higher in fish fed with CSM-TC. The results showed that CSM-TC significantly increased the activities of alkaline phosphatase, complement 3, and complement 4 enzymes (p < 0.05). The results showed that dietary CSM-TC increased the activities of hepatic superoxide dismutase and total antioxidant capacity enzymes. Compared with other groups, the hepatic relative expressions of Nrf2, HO-1, and GSH-Px were significantly higher in fish fed with CSM-TC. The results showed that dietary CSM-TC increased the activities of intestinal chymotrypsin, lipase, and α-amylase enzymes. A CSM-TC diet significantly increased the relative expressions of IL-10, ZO-1, Occludin, Claudin-3, and Claudin-15 (p < 0.05). The results showed that CSM-C significantly increased the index of Ace and Chao1 (p < 0.05). In conclusion, a high-fermented cottonseed meal diet can have detrimental effects on physiological health in golden pompano, while adding 1% ECPC and 0.25% taurine can improve hepatic and intestinal health via attenuating inflammation and oxidative stress.
Numerical Study of Heat Transfer Enhancement Using Nano-Encapsulated Phase Change (NPC) Slurries in Wavy Microchannels
Authors: Zaw Myo Min , Zhu Liang , Ma Ronghui
Published: October 2024

Researchers have attempted to improve heat transfer in mini/microchannel heat sinks by dispersing nano-encapsulated phase change (NPC) materials in base coolants. While NPC slurries have demonstrated improved heat transfer performance, their applications are limited by decreasing enhancement at increased flow rates. To address this challenge, the present study numerically investigates the effects of wavy channels on the performance of NPC slurries. Simulation results reveal that a wavy channel induces Dean vortices that intensify the mixing of the working fluid and enlarge the melting fractions of the NPC material, thus offering a significantly higher heat transfer efficiency than a straight channel. Moreover, heat transfer enhancement by NPC slurries varies with the imposed heat flux and flow rate. Interestingly, the maximum heat transfer enhancement obtained with the wavy channel not only exceeds the straight one, but also occurs at a higher heat flux and faster flow rate. This finding demonstrates the advantage of wavy channels in management of intensive heat fluxes with NPC slurries. The study also investigates wavy channels with varying amplitude and wavelength. Increasing the wave aspect ratio from 0.2 to 0.588 strengthens Dean vortices and consequently increases the Nusselt number, optimal heat flux, and overall thermal performance factor.
Concurrence of Inactivation Enzyme-Encoding Genes tet(X), blaEBR, and estT in Empedobacter Species from Chickens and Surrounding Environments
Authors: Chen Chong , Lv Yilin , Wu Taotao , Liu Jing , Guo Yanan , Huang Jinlin
Published: October 2024

The emergence of inactivation enzyme-encoding genes tet(X), blaEBR, and estT challenges the effectiveness of tetracyclines, β-lactams, and macrolides. This study aims to explore the concurrence and polymorphism of their variants in Empedobacter sp. strains from food-producing animals and surrounding environments. A total of eight tet(X) variants, seven blaEBR variants, and seven estT variants were detected in tet(X)-positive Empedobacter sp. strains (6.7%) from chickens, sewage, and soil, including 31 Empedobacter stercoris and 6 novel species of Taxon 1. All of them were resistant to tigecycline, tetracycline, colistin, and ciprofloxacin, and 16.2% were resistant to meropenem, florfenicol, and cefotaxime. The MIC90 of tylosin, tilmicosin, and tildipirosin was 128 mg/L, 16 mg/L, and 8 mg/L, respectively. Cloning expression confirmed that tet(X6) and the novel variants tet(X23), tet(X24), tet(X25), tet(X26), and tet(X26.2) conferred high-level tigecycline resistance, while all of the others exhibited relatively low-level activities or were inactivated. The bacterial relationship was diverse, but the genetic environments of tet(X) and blaEBR were more conserved than estT. An ISCR2-mediated tet(X6) transposition structure, homologous to those of Acinetobacter sp., Proteus sp., and Providencia sp., was also identified in Taxon 1. Therefore, the tet(X)-positive Empedobacter sp. strains may be ignored and pose a serious threat to food safety and public health.
Recovery of Novel Sequence Variants in Chemically Mutagenized Seed and Vegetatively Propagated Coffea arabica L.
Authors: Till Bradley J. , Jiménez-Madrigal José P. , Herrera-Estrella Alfredo , Atriztán-Hernández Karina , Gatica-Arias Andrés
Published: October 2024

The negative effects of climate change impact both farmers and consumers. This is exemplified in coffee, one of the most widely consumed beverages in the world. Yield loss in high-quality Coffea arabica L., due to the spread of coffee leaf rust (Hemileia vastatrix), results in lower income for subsistence farmers and volatile prices in markets and cafes. Genetic improvement of crops is a proven approach to support sustainable production while mitigating the effects of biotic and abiotic stresses and simultaneously maintaining or improving quality. However, the improvement of many species, including coffee, is hindered by low genetic diversity. This can be overcome by inducing novel genetic variation via treatment of seeds or cells with mutagens. To evaluate this approach in coffee, mutant populations created by incubating seed or embryogenic calli with the chemical mutagens ethyl methanesulphonate or sodium azide were subject to reduced-representation DNA sequencing using the ddRADseq approach. More than 10,000 novel variants were recovered. Functional analysis revealed hundreds of sequence changes predicted to be deleterious for gene function. We discuss the challenges of unambiguously assigning these variants as being caused by the mutagenic treatment and describe purpose-built computational tools to facilitate the recovery of novel genetic variation from mutant plant populations.
Obtaining Lignin from Nutshells under Mild Extraction Conditions and Its Use as a Biostimulant in Tomato Seedlings
Authors: Díaz-Elizondo José Alejandro , Ayala-Velazco Azrrael , Benavides-Mendoza Adalberto , Enriquez-Medrano Francisco Javier , Medrano-Macías Julia
Published: October 2024

Biostimulants are an important alternative to improve and promote higher efficiency in cropping systems. Although the biostimulant industry has been developing for several years, there are still areas of opportunity for new sources of biostimulants as well as new ecofriendly extraction techniques that allow for a circular economy and the reuse of waste. Lignin is a heteropolymer that constitutes about 40% of the plant cell wall. A great source of lignin is agrowastes, giving it added value. Recently, its use has been tested in agronomy as a carrier of nutrients and pesticides. Walnuts are produced on a large scale in Northern Mexico, and the shell represents between 15 and 40% of its total weight. However, to obtain this biopolymer, to date, non-environmentally friendly techniques have been used; for this reason, it is necessary to find extraction alternatives to make this proposal sustainable. In this work, the obtaining and characterization of lignin through mild extraction conditions from nutshells and its evaluation as a biostimulant on the growth of tomato seedlings are reported. Lignin was extracted by hydrolysis with a mixture of acetic acid and distilled water (65:35 v/v). The results showed that it was possible to obtain 15% (w/w) lignin using mild solvents, evidenced by thermogravimetric analysis (TGA), proton magnetic nuclear resonance (H-RMN), and infrared (IR). Subsequently, lignin solutions were prepared at different concentrations, 0, 10, 50, and 100 ppm, and applied via foliar weekly to tomato seedlings. A greater fresh weight of the stem was found with 10 and 50 ppm, and the height and the fresh biomass increased with the three concentrations (10, 50, and 100 ppm), concluding that lignin extracted from nutshells using mild conditions can act as a plant biostimulant.
Integrated Metabolome and Transcriptome Analyses Reveal the Mechanisms Regulating Flavonoid Biosynthesis in Blueberry Leaves under Salt Stress
Authors: Ma Bin , Song Yan , Feng Xinghua , Guo Pu , Zhou Lianxia , Jia Sijin , Guo Qingxun , Zhang Chunyu
Published: October 2024

The flavonoids play important roles in plant salt tolerance. Blueberries (Vaccinium spp.) are extremely sensitive to soil salt increases. Therefore, improving the salt resistance of blueberries by increasing the flavonoid content is crucial for the development of the blueberry industry. To explore the underlying molecular mechanism, we performed an integrated analysis of the metabolome and transcriptome of blueberry leaves under salt stress. We identified 525 differentially accumulated metabolites (DAMs) under salt stress vs. control treatment, primarily including members of the flavonoid class. We also identified 20,920 differentially expressed genes (DEGs) based on transcriptome data; of these, 568 differentially expressed transcription factors (TFs) were annotated, and bHLH123, OsHSP20, and HSP20 TFs might be responsible for blueberry leaf salt tolerance. DEGs involved in the flavonoid biosynthesis pathway were significantly enriched at almost all stages of salt stress. Salt treatment upregulated the expression of most flavonoid biosynthetic pathway genes and promoted the accumulation of flavonols, flavonol glycosides, flavans, proanthocyanidins, and anthocyanins. Correlation analysis suggested that 4-coumarate CoA ligases (4CL5 and 4CL1) play important roles in the accumulation of flavonols (quercetin and pinoquercetin) and flavan-3-ol (epicatechin and prodelphinidin C2) under salt stress, respectively. The flavonoid 3′5′-hydroxylases (F3′5′H) regulate anthocyanin (cyanidin 3-O-beta-D-sambubioside and delphinidin-3-O-glucoside chloride) biosynthesis, and leucoanthocyanidin reductases (LAR) are crucial for the biosynthesis of epicatechin and prodelphinidin C2 during salt stress. Taken together, it is one of the future breeding goals to cultivate salt-resistant blueberry varieties by increasing the expression of flavonoid biosynthetic genes, especially 4CL, F3′5′H, and LAR genes, to promote flavonoid content in blueberry leaves.
Do Foreign Investors Underperform or Outperform Domestic Investors in Trading Activities? Evidence from Indonesia
Authors: Koesrindartoto Deddy P. , Aaron Aurelius , Wang Shuqi
Published: October 2024

The performance of foreign investors relative to domestic investors has been a subject of mixed evidence. While foreign investors are often perceived to underperform due to an information disadvantage, they are also known for their aggressive trading and superior performance in initiated orders. We provide further clarity on this issue. Specifically, by analyzing over five million transactions on the Jakarta Stock Exchange, our findings reveal that foreign investors consistently outperform domestic investors in terms of both annualized returns and profit amounts. Further investigation attributes this outperformance to the higher sophistication of foreign investors, who demonstrate superior stock-picking abilities and effective growth investing strategies.
Cdk1 Deficiency Extends the Postnatal Window of Cardiomyocyte Proliferation and Restores Cardiac Function after Myocardial Infarction
Authors: Mahiny Donya , Hauck Ludger , Premsingh Benny , Grothe Daniela , Billia Filio
Published: October 2024

Cyclin-dependent kinase 1 (Cdk1) is a master regulator of the G2-M transition between DNA replication and cell division. This study investigates the regulation of cardiomyocyte (CM) proliferation during the early neonatal period and following ischemic injury in adult mice. We analyzed cell cycle dynamics with the assessment of DNA synthesis, and cytokinesis in murine hearts during the first 15 days after birth. A distinct proliferative block was observed at 1 day, followed by a second wave of DNA synthesis at 4 days, leading to CM binucleation (CMBN) by day 5. Genome-wide mRNA profiling revealed the differential expression of cell cycle regulatory genes during this period, with a downregulation of factors involved in cell division and mitosis. The loss of Cdk1 impaired CMBN but extended the neonatal CM proliferation window until day 10 post-birth. In adult hearts, the cardiac-specific ablation of Cdk1 triggered CM proliferation post-myocardial-infarction (MI) in specific zones, driven by the activation of EGFR1 signaling and suppression of the anti-proliferative p38 and p53 signaling. This was accompanied by restoration of fractional shortening, mitochondrial function, and decreased reactive oxygen species. Additionally, cardiac hypertrophy was mitigated, and survival rates post-MI were increased in Cdk1-knockout mice. These findings reveal a novel role of Cdk1 in regulating cell cycle exit and re-entry in differentiated CMs and offer insights into potential strategies for cardiac repair.
NBF2, an Algal Fiber-Rich Formula, Reverses Diabetic Dyslipidemia and Hyperglycemia In Vivo
Authors: Ngatu Nlandu Roger , Hossain Akram , Maruo Nao , Akumwami Steeve , Rahman Asadur Md. , Eitoku Masamitsu , Kanda Kanae , Nishiyama Akira , Suganuma Narufumi , Hirao Tomohiro
Published: October 2024

Ulva prolifera, known as Aonori in Japan, is an edible alga species that is mass-cultivated in Japan. Supplementation with Aonori-derived biomaterials has been reported to enhance metabolic health in previous studies. This was an experimental study that evaluated the metabolic health effects of NBF2, a formula made of algal and junos Tanaka citrus-derived biomaterials, on obesity and type 2 diabetes (T2DM). We used 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats that were assigned randomly to three groups of six animals: a high-dose NBF2 drink (20 mg/kg) group, a low-dose (10 mg/kg) NBF2 drink group and the control group that received 2 mL of tap water daily for a total of six weeks. We also used eight LETO rats as the normal control group. In addition to the glucose tolerance test (OGTT), ELISA and real-time PCR assays were performed. High-dose and lowdose NBF2 improved insulin sensitivity, as well as glycemic and lipid profiles, as compared with control rats. The OGTT showed that both NBF2 groups and LETO rats had normalized glycemia by the 90-min time-point. NBF2 up-regulated PPARα/γ-mRNA and Sirt2-mRNA gene expressions in BAT and improved the blood pressure profile. These findings suggest that the NBF2 formula, which activates PPAR-α/γ mRNA and Sirt2-mRNA, may reverse dyslipidemia and hyperglycemia in T2DM.
Synthesis and Preliminary Studies for In Vitro Biological Activity of Two New Water-Soluble Bis(thio)carbohydrazones and Their Copper(II) and Zinc(II) Complexes
Authors: Zavaroni Alessio , Riva Elena , Borghesani Valentina , Donati Greta , Santoro Federica , D’Amore Vincenzo Maria , Tegoni Matteo , Pelosi Giorgio , Buschini Annamaria , Rogolino Dominga , Carcelli Mauro
Published: October 2024

Research in the field of metallodrugs is continually increasing. However, it is often limited by the poor solubility in water of the metal complexes. To try to overcome this problem, the two new ligands bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)thiocarbohydrazone (bis-TCH, Na2H4L1) and bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)carbohydrazone (bis-CH, Na2H4L2) were synthesized and characterized, both achieving high solubility in water. The speciation of the ligands and their coordinating behaviour towards the biologically relevant Cu(II) and Zn(II) ions were studied spectroscopically and potentiometrically, determining the pKas of the ligands and the formation constants of the complex species. The monometallic and bimetallic Cu(II) and Zn(II) complexes were isolated, and the single-crystal X-ray structure of [Cu2(NaHL1)(H2O)7].3.5H2O was discussed. Finally, preliminary studies of the in vitro cytotoxic properties of the new compounds were started on normal (Hs27) and cancer (U937) cell lines. bis-TCH was able to induce a growth inhibition effect between 40% and 45% in both cell lines; bis-CH did not produce a reduction in cell viability in Hs27 cells but revealed mild antiproliferative activity after 72 h of treatment in U937 cancer cells (GI50 = 46.5 ± 4.94 μg/mL). Coordination of the Cu(II) ions increased the toxicity of the compounds, while, in contrast, Zn(II) complexes were not cytotoxic.
MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import
Authors: Xu Tao , Chen Guilan
Published: October 2024

Ferroptosis is a recently identified iron-dependent programmed cell death with lipid peroxide accumulation and condensation and compaction of mitochondria. A recent study indicated that ferroptosis plays a pivotal role in ischemic cardiac injury with the mechanisms remain largely unknown. This study demonstrates that when an iron overload occurs in the ischemia/reperfusion cardiac tissues, which initiates myocardial ferroptosis, the expression levels of mitochondrial inner membrane protein MPV17 are reduced. Overexpression of MPV17 delivered via adenovirus significantly reduced ferroptosis in both cardiomyocytes with high levels of iron and cardiac I/R tissues. Mitochondrial glutathione (mtGSH), crucial for reactive oxygen species scavenging and mitochondrial homeostasis maintenance, is depleted in myocardial ferroptosis caused by iron overload. This mechanistic study shows that MPV17 can increase mitochondrial glutathione levels through maintaining the protein homeostasis of SLC25A10, which is a mitochondrial inner-membrane glutathione transporter. The absence of MPV17 in iron overload resulted in the ubiquitination-dependent degradation of SLC25A10, leading to impaired mitochondrial glutathione import. Moreover, we found that MPV17 was the targeted gene of Nrf2, which plays a pivotal role in preventing lipid peroxide accumulation and ferroptosis. The decreased expression levels of Nrf2 led to the inactivation of MPV17 in iron overload-induced myocardial ferroptosis. In summary, this study demonstrates the critical role of MPV17 in protecting cardiomyocytes from ferroptosis and elucidates the Nrf2-MPV17-SLC25A10/mitochondrial glutathione signaling pathway in the regulation of myocardial ferroptosis.
Pleiotrophin Activates cMet- and mTORC1-Dependent Protein Synthesis through PTPRZ1—The Role of ανβ3 Integrin
Authors: Mourkogianni Eleni , Karavasili Katerina , Xanthopoulos Athanasios , Enake Michaela-Karina , Menounou Lydia , Papadimitriou Evangelia
Published: October 2024

Pleiotrophin (PTN) is a secreted factor that regulates endothelial cell migration through protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) and αvβ3 integrin. Genetic deletion of Ptprz1 results in enhanced endothelial cell proliferation and migration, due to the decreased expression of β3 integrin and the subsequent, enhanced cMet phosphorylation. In the present study, we investigated the effect of PTN and PTPRZ1 on activating the mTORC1 kinase and protein synthesis and identified part of the implicated signaling pathway in endothelial cells. PTN or genetic deletion of Ptprz1 activates protein synthesis in a mTORC1-dependent manner, as shown by the enhanced phosphorylation of the mTORC1-downstream targets ribosomal protein S6 kinase 1 (SK61) and 4E-binding protein 1 (4EBP1) and the upregulation of HIF-1α. The cMet tyrosine kinase inhibitor crizotinib abolishes the stimulatory effects of PTN or PTPRZ1 deletion on mTORC1 activation and protein synthesis, suggesting that mTORC1 activation is downstream of cMet. The mTORC1 inhibitor rapamycin abolishes the stimulatory effect of PTN or PTPRZ1 deletion on endothelial cell migration, suggesting that mTORC1 is involved in the PTN/PTPRZ1-dependent cell migration. The αvβ3 integrin blocking antibody LM609 and the peptide PTN112–136, both known to bind to ανβ3 and inhibit PTN-induced endothelial cell migration, increase cMet phosphorylation and activate mTORC1, suggesting that cMet and mTORC1 activation are required but are not sufficient to stimulate cell migration. Overall, our data highlight novel aspects of the signaling pathway downstream of the PTN/PTPRZ1 axis that regulates endothelial cell functions.
Photodynamic Therapy against Colorectal Cancer Using Porphin-Loaded Arene Ruthenium Cages
Authors: Ghaddar Suzan , Pinon Aline , Gallardo-Villagran Manuel , Massoud Jacquie , Ouk Catherine , Carrion Claire , Diab-Assaf Mona , Therrien Bruno , Liagre Bertrand
Published: October 2024

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC.
Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4+ T-Cell Subpopulations Identified by Comparative Proteomic Analysis
Authors: Vázquez-Mera Sara , Miguéns-Suárez Pablo , Martelo-Vidal Laura , Rivas-López Sara , Uller Lena , Bravo Susana B. , Domínguez-Arca Vicente , Muñoz Xavier , González-Barcala Francisco J. , Nieto Fontarigo Juan J. , Salgado Francisco J.
Published: October 2024

Several studies have described the proteomic profile of different immune cell types, but only a few have also analysed the content of their delivered small extracellular vesicles (sEVs). The aim of the present study was to compare the protein signature of sEVs delivered from granulocytes (i.e., neutrophils and eosinophils) and CD4+ T cells (i.e., TH1, TH2, and TH17) to identify potential biomarkers of the inflammatory profile in chronic inflammatory diseases. Qualitative (DDA) and quantitative (DIA-SWATH) analyses of in vitro-produced sEVs revealed proteome variations depending on the cell source. The main differences were found between granulocyte- and TH cell-derived sEVs, with a higher abundance of antimicrobial proteins (e.g., LCN2, LTF, MPO) in granulocyte-derived sEVs and an enrichment of ribosomal proteins (RPL and RPS proteins) in TH-derived sEVs. Additionally, we found differentially abundant proteins between neutrophil and eosinophil sEVs (e.g., ILF2, LTF, LCN2) and between sEVs from different TH subsets (e.g., ISG15, ITGA4, ITGB2, or NAMPT). A “proof-of-concept” assay was also performed, with TH2 biomarkers ITGA4 and ITGB2 displaying a differential abundance in sEVs from T2high and T2low asthma patients. Thus, our findings highlight the potential use of these sEVs as a source of biomarkers for diseases where the different immune cell subsets studied participate, particularly chronic inflammatory pathologies such as asthma or chronic obstructive pulmonary disease (COPD).
Modulation of the Arabidopsis Starch Metabolic Network by the Cytosolic Acetyl-CoA Pathway in the Context of the Diurnal Illumination Cycle
Authors: Wang Lei , Foster Carol M. , Mentzen Wieslawa I. , Tanvir Rezwan , Meng Yan , Nikolau Basil J. , Wurtele Eve Syrkin , Li Ling
Published: October 2024

The starch metabolic network was investigated in relation to other metabolic processes by examining a mutant with altered single-gene expression of ATP citrate lyase (ACL), an enzyme responsible for generating cytosolic acetyl-CoA pool from citrate. Previous research has shown that transgenic antisense plants with reduced ACL activity accumulate abnormally enlarged starch granules. In this study, we explored the underlying molecular mechanisms linking cytosolic acetyl-CoA generation and starch metabolism under short-day photoperiods. We performed transcriptome and quantification of starch accumulation in the leaves of wild-type and antisense seedlings with reduced ACL activity. The antisense-ACLA mutant accumulated more starch than the wild type under short-day conditions. Zymogram analyses were conducted to compare the activities of starch-metabolizing enzymes with transcriptomic changes in the seedling. Differential expression between wild-type and antisense-ACLA plants was detected in genes implicated in starch and acetyl-CoA metabolism, and cell wall metabolism. These analyses revealed a strong correlation between the transcript levels of genes responsible for starch synthesis and degradation, reflecting coordinated regulation at the transcriptomic level. Furthermore, our data provide novel insights into the regulatory links between cytosolic acetyl-CoA metabolism and starch metabolic pathways.
Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis
Authors: Fan Wen , Pan Maoxing , Zheng Chuiyang , Shen Haiyan , Pi Dajin , Song Qingliang , Liang Zheng , Zhen Jianwei , Pan Jinyue , Liu Lianghao , Yang Qinhe , Zhang Yupei
Published: October 2024

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.
A Review on Apple Pomace Bioactives for Natural Functional Food and Cosmetic Products with Therapeutic Health-Promoting Properties
Authors: Vandorou Maria , Plakidis Christos , Tsompanidou Ilektra Maria , Adamantidi Theodora , Panagopoulou Eirini A. , Tsoupras Alexandros
Published: October 2024

Apples are consumed lavishly worldwide, while demand is increasing for the management of the huge apple-waste amounts that lead to significant disposal costs and ecological issues. Additionally, apples represent fruits with several bioactive constituents, which are key factors in a healthy, balanced diet. In the present study, an extensive review is presented regarding the bioactive compounds of an apple processing by-product, namely apple pomace, mentioning their significance as viable ingredients/substances in foods and cosmetics aiming at chronic disease prevention and health promotion. Apple pomace contains several constituents, such as polar lipids, phenolics, vitamins and dietary fibers, with potential antioxidant, anti-inflammatory, anti-thrombotic, anti-aging and skin-protecting properties, and thus, they may contribute to minimizing the risk of various health conditions. Additionally, the mechanisms of action of such functional bioactives from apple pomace exert health benefits that will be examined, while the potential synergistic effects will also be investigated. Moreover, we will present the methods and techniques needed for the utilization of apple pomace in the appropriate form, such as powder, extracts, essential oil and so on, and their several applications in the food and cosmeceutical industry sectors, which summarize that apple pomace represents an ideal alternative to synthetic bioactive compounds.
Compound Heterozygous RYR1 Variants in a Patient with Severe Congenital Myopathy: Case Report and Comparison with Additional Cases of Recessive RYR1-Related Myopathy
Authors: Janßen Sören , Erbe Leoni S. , Kneifel Moritz , Vorgerd Matthias , Döring Kristina , Lubieniecki Krzysztof P. , Lubieniecka Joanna M. , Gerding Wanda M. , Casadei Nicolas , Güttsches Anne-Katrin , Heyer Christoph , Lücke Thomas , Nguyen Hoa Huu Phuc , Köhler Cornelia , Hoffjan Sabine
Published: October 2024

Pathogenic variants in the ryanodine receptor 1 (RYR1) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype–phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient’s phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype–phenotype correlations.
Electrocardiographic Changes, Mortality, and Late Period Findings in Methyl Alcohol Poisoning
Authors: Coskun Abuzer , Demirci Burak , Oymak Ismail , Ferhatlar Enes , Eren Sevki Hakan
Published: October 2024

Background: Methyl alcohol poisoning (MAP) is a common commercial compound that can lead to significant morbidity and mortality when exposed to high levels. This study aims to describe MAP-related electrocardiography (ECG) changes and post-acute late complications. Materials and Methods: The study was conducted through a retrospective data review between 2017 and 2023. Patient data were recorded, including demographic information, medication use, and laboratory results. Twelve-lead ECG recordings were evaluated and the results were recorded. The cases included in the study were grouped according to QTc distance, ECG findings, late-term complications, treatment status, and mortality. Results: The mean age of all cases included in the study (n = 227) was 43.23 ± 11.11 years, 8 (3.5%) cases were female, and the age distribution was between 19 and 68 years (p = 0.792). The age distribution of QTc groups was not significant (p = 0.792). The mean QTc distance was 442.7 ± 60.1 ms in all cases (n = 227) and 514.08 ± 5.45 ms in cases with mortality (n = 49) (p < 0.001). The mean time to application of the patients to the hospital (n = 227) was 19.1 ± 4.61 h, and blood sugar was 130.7 ± 32.09 mg/dL (p < 0.001). In addition, the mean pH of the cases (n = 227) was 7.14 ± 0.2, bicarbonate was 17.17 ± 4.86 mmol/L, the base deficit was −6.21 ± 3.18 mmol/L, the anion gap was 19.36 ± 7.31 mmol/L, and lactate was 4.82 ± 2.45 mmol/L (p < 0.001). Mortality occurred in 49 (21.6%) of the patients, and all of them were in-hospital deaths. In all cases where mortality occurred, pH was below 6.93 ± 0.22 and severe acidosis was directly related to death. MAP, sinus tachycardia in 31 (13.7%) cases, bradycardia in 8 (3.5%), atrial fibrillation in 5 (2.2%), accelerated idioventricular rhythm in 3 (1.3%), and 11 (4.8%), left bundle branch block, and right bundle branch block were detected in 22 (9.7%). All of these ECG findings were newly developed conditions with no previous history. In the 6-month follow-up after discharge, 4 (1.8%) of the cases developed neurological deficit, 15 (6.6%) had acute coronary syndrome and severe heart failure, 23 (10.1%) had permanent blindness, 6 (2.7%) had renal failure, and 6 (2.7%) had pancreatitis. Conclusions: Methyl alcohol poisoning can cause various ECG changes; sinus tachycardia, nonspecific changes, and QTc prolongation are the most common findings. These changes are more pronounced in cases of severe acidosis. Patients should be warned of late signs of MAP.