bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Effect of Soil Water Conditions on the Development and Water Requirements of Adult Oil Palm (Elaeis guineensis Jacq.) in the Northern Region of Colombia
Authors: Delgado Tulia , Ladino Greydy , Arias Nolver
Published: September 2024

Sustainable water management is a key approach for enhancing the productivity of oil palm trees while addressing the impacts of climate change and variability. Determining the water needs of a crop is crucial for the appropriate application of water. This research was carried out in two plantations in Agustín Codazzi, Colombia, using a completely randomized design. This study involved examining the impacts of five different water conditions (50, 150, 300, 450, and 600 L per day) on the growth and yields of mature oil palm trees (aged 10–17 years), and their water consumption was calculated using the water balance method. The results indicated that the crop was negatively affected by daily water applications of 300, 150, and 50 L per day, showing statistically significant differences (p < 0.05) when compared to the 450 and 600 L per day treatments, particularly in terms of leaf emergence, leaf area index, and yield (tons per hectare). The 50 L per day treatment resulted in the most substantial decrease in yield (around 26%), primarily attributed to a reduction in the number of bunches. The most favorable crop responses were observed with water applications of 450 and 600 L per day, aligning with the crop’s potential evapotranspiration values (ranging between 5.4 and 5.7 mm per day) and yielding crop coefficients of 0.88 and 0.9, respectively. Notably, these values varied between dry and rainy seasons, peaking between December and March.
Enhancing Panax notoginseng Leaf Disease Classification with Inception-SSNet and Image Generation via Improved Diffusion Model
Authors: Wang Ruoxi , Zhang Xiaofan , Yang Qiliang , Lei Lian , Liang Jiaping , Yang Ling
Published: September 2024

The rapid and accurate classification of Panax notoginseng leaf diseases is vital for timely disease control and reducing economic losses. Recently, image classification algorithms have shown great promise for plant disease diagnosis, but dataset quantity and quality are crucial. Moreover, classifying P. notoginseng leaf diseases faces severe challenges, including the small features of anthrax and the strong similarity between round spot and melasma diseases. In order to address these problems, we have proposed an ECA-based diffusion model and Inception-SSNet for the classification of the six major P. notoginseng leaf diseases, namely gray mold, powdery mildew, virus infection, anthrax, melasma, and round spot. Specifically, we propose an image generation scheme, in which the lightweight attention mechanism, ECA, is used to capture the dependencies between channels for improving the dataset quantity and quality. To extract disease features more accurately, we developed an Inception-SSNet hybrid model with skip connection, attention feature fusion, and self-calibrated convolutional. These innovative methods enable the model to make better use of local and global information, especially when dealing with diseases with similar features and small targets. The experimental results show that our proposed ECA-based diffusion model FID reaches 42.73, compared with the baseline model, which improved by 74.71%. Further, we tested the classification model using the data set of P. notoginseng leaf disease generation, and the accuracy of 11 mainstream classification models was improved. Our proposed Inception-SSNet classification model achieves an accuracy of 97.04% on the non-generated dataset, which is an improvement of 0.11% compared with the baseline model. On the generated dataset, the accuracy reached 99.44%, which is an improvement of 1.02% compared to the baseline model. This study provides an effective solution for the monitoring of Panax notoginseng diseases.
Genome-Wide Identification and Analysis of the Aux/IAA Gene Family in Rosa hybrida—“The Fairy”: Evidence for the Role of RhIAA25 in Adventitious Root Development
Authors: Zhang Wuhua , Zhang Yifei , Huangfu Minge , Fan Yingdong , Zhang Jinzhu , Yang Tao , Che Daidi , Dong Jie
Published: September 2024

Propagation of cuttings is the primary method of rose multiplication. Aux/IAA, early response genes to auxin, play an important role in regulating the process of adventitious root formation in plants. However, systematic research on the identification of RhAux/IAA genes and their role in adventitious root formation in roses is lacking. In this study, 34 RhAux/IAA genes were identified by screening the rose genome, distributed on seven chromosomes, and classified into three clades based on the evolutionary tree. An analysis of the cis-acting elements in the promoters of RhAux/IAA genes revealed the presence of numerous elements related to plant hormones, the light signal response, the growth and development of plants, and abiotic stress. RNA-seq analysis identified a key RhIAA25 gene that may play an important role in the generation of adventitious roots in roses. Subcellular localization, yeast self-activation, and tissue-specific expression experiments indicated that RhIAA25 encoded a nuclear protein, had no yeast self-activated activity, and was highly expressed in the stem. The overexpression of RhIAA25 promoted the elongation of the primary root in Arabidopsis but inhibited adventitious root formation. This study systematically identified and analyzed the RhAux/IAA gene family and identified a key gene, RhIAA25, that regulates adventitious root generation in roses. This study offers a valuable genetic resource for investigating the regulatory mechanism of adventitious root formation in roses.
Growth Stimulation of Tropical Grass (Megathyrsus maximus Jacq.) by Humic Substances and Herbaspirillum seropedicae
Authors: Canellas Luciano P. , Canellas Natália A. , Silva Rakiely M. , Novotny Etelvino H. , Olivares Fabio L.
Published: September 2024

This study aimed to evaluate the effect of soluble humic substances and plant-growth-promoting bacteria on the vegetative growth of Mombaça grass. A greenhouse experiment was conducted to study the effects of foliar applications of humic substances (0, 12, 24, 48, and 96 mg C L−1) on the growth of Mombaça fifteen days after germination. After determining the optimal concentration range, a field trial was carried out in which humic substances at the best concentration were applied simultaneously with Herbaspirillum seropedicae strain UENF-H19 fifteen days after germination in three replicates. The best growth of Mombaça in the greenhouse was obtained with 48 mg C of the humic substance L−1, which promoted a shoot fresh weight 80% higher than in the control treatment. The increase was almost identical to that observed during the 50-week field experiment in plots treated with humic substances combined with H. seropedicae. The treated plants produced an 81% higher shoot fresh weight than the control, with no dry mass, nitrogen content, or crude protein change during the one-year evaluation period. Despite the efficiency of the selected microbial inoculants under controlled-environment experiments, the agronomical significance under field conditions remains a subject of debate and improvement. The present study demonstrates that combining Herbaspirillum seropedicae with humic substances (plural) could significantly increase pasture production under field conditions.
Morpho-Geometric Description of the Skulls and Mandibles of Brown Bears (Ursus arctos) from the Dancing Bear Belitsa Park
Authors: Ruzhanova-Gospodinova Iliana Stefanova , Vladova Silvi , Szara Tomasz , Tandir Faruk , Szara Ewa , Yalin Ebru Eravci , Gündemir Ozan
Published: September 2024

The present study aimed to describe the skull and mandibles of the brown bear (U. arctos) from the Dancing Bear Belitsa Park using advanced 3D morpho-geometric techniques. The objective was to explore how sexual dimorphism and size influence cranial structures using advanced 3D geometric morphometric methods. Three-dimensional models of the skulls and mandibles of 12 brown bears were used. Differences in skull morphology between male and female brown bears were observed in this study. The male brown bear skull, larger than the female, exhibited a more pronounced extension of the upper part of the nuchal region towards the posterior. Additionally, the posterior part of the frontal region appeared notably thinner in male brown bears compared to females. Analysis of the mandible revealed that the masseteric fossa was more developed in males than females. These shape differences between males and females were found to be influenced by body size. Statistical analyses indicated a significant allometric effect of body size on skull PC1 values, suggesting that giant bears tend to have more elongated skulls. This implies a relationship in which larger individuals exhibit greater cranial elongation. In contrast, mandible PC1 values showed no size-related variation, indicating that mandibular shape is less influenced by overall body size. However, PC2 values in the mandible increased significantly with larger specimens, indicating a larger masseteric fossa in larger bears. This morphological adaptation potentially enhances feeding efficiency and bite strength in larger individuals, reflecting functional adaptations in brown-bear mandibular morphology. These findings contribute to our understanding of sexual dimorphism and size-related morphological adaptations in brown bears, providing insights into their adaptation biology and ecological roles within their habitats.
Long-Term Immunity against SARS-CoV-2 Wild-Type and Omicron XBB.1.5 in Indonesian Residents after Vaccination and Infection
Authors: Karismananda  , Hasyim Ammar Abdurrahman , Sakamoto Akihiko , Yamagata Kyouhei , Zainal Kartika Hardianti , Suparman Desi Dwirosalia Ningsih , Yustisia Ika , Hardjo Marhaen , Kadir Syahrijuita , Iyori Mitsuhiro , Yoshida Shigeto , Yusuf Yenni
Published: September 2024

In the post-pandemic era, evaluating long-term immunity against COVID-19 has become increasingly critical, particularly in light of continuous SARS-CoV-2 mutations. This study aimed to assess the long-term humoral immune response in sera collected in Makassar. We measured anti-RBD IgG levels and neutralization capacity (NC) against both the Wild-Type (WT) Wuhan-Hu and Omicron XBB.1.5 variants across groups of COVID-19-vaccinated individuals with no booster (NB), single booster (SB), and double booster (DB). The mean durations since the last vaccination were 25.11 months, 19.24 months, and 16.9 months for the NB, SB, and DB group, respectively. Additionally, we evaluated the effect of breakthrough infection (BTI) history, with a mean duration since the last confirmed infection of 21.72 months. Our findings indicate fair long-term WT antibody (Ab) titers, with the DB group showing a significantly higher level than the other groups. Similarly, the DB group demonstrated the highest anti-Omicron XBB.1.5 Ab titer, yet it was insignificantly different from the other groups. Although the level of anti-WT Ab titers was moderate, we observed near-complete (96–97%) long-term neutralization against the WT pseudo-virus for all groups. There was a slight decrease in NC against Omicron XBB.1.5 compared to the WT among all groups, as DB group, SB group, and NB group showed 80.71 ± 3.9%, 74.29 ± 6.7%, and 67.2 ± 6.3% neutralization activity, respectively. A breakdown analysis based on infection and vaccine status showed that booster doses increase the NC against XBB.1.5, particularly in individuals without BTI. Individuals with BTI demonstrate a better NC compared to their counterpart uninfected individuals with the same number of booster doses. Our findings suggest that long-term immunity against SARS-CoV-2 persists and is effective against the mutant variant. Booster doses enhance the NC, especially among uninfected individuals.
Health-Promoting Properties of Pectin–Polyphenol Complex Extracted from Olive Oil By-Product Alperujo: Antioxidant, Antiproliferative, and Anti-Inflammatory Activities
Authors: Bermúdez-Oria Alejandra , Castejón María Luisa , Rubio-Senent Fátima , Rodríguez-Gutiérrez Guillermo , Fernández-Bolaños Juan
Published: September 2024

This research explores the health-promoting properties of the pectin–polyphenol complex extracted from alperujo, a by-product of olive oil production. This study investigates the chemical composition and antioxidant activity of the extracts, revealing their high antioxidant activity in vitro. Cell viability assays conducted on colon carcinoma cells (Caco-2) demonstrate the inhibitory effect of the extracts on cell proliferation. However, the extracts do not affect the viability of differentiated Caco-2 cells, suggesting a selective antiproliferative action. Additionally, the extracts reduce intracellular reactive oxygen species (ROS) and nitrite (NO) production in LPS-stimulated murine peritoneal macrophages. Furthermore, the extracts exhibit anti-inflammatory effects by downregulating the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in these macrophages. These findings highlight the potential of pectin–polyphenol complexes as functional ingredients with significant health benefits, demonstrating antioxidant, antiproliferative, and anti-inflammatory properties.
Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats
Authors: Dulf Patricia Lorena , Coadă Camelia Alexandra , Florea Adrian , Moldovan Remus , Baldea Ioana , Dulf Daniel Vasile , Blendea Dan , Filip Adriana Gabriela
Published: September 2024

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.
Study on the Response Mechanism of Climate and Land Use Change to Evapotranspiration in Aksu River Basin
Authors: Zheng Gang , Wei Guanghui , Han Fanghong , Cao Yan , Gao Fan
Published: September 2024

Research on evapotranspiration and its drivers in the Aksu River Basin from the perspectives of climate change and land use is of great significance for promoting the efficient use and precise allocation of its water resources. Theil-Sen median trend analysis (T-S) and the Mann–Kendall nonparametric test (M-K), in addition to correlation analysis, partial correlation analysis, complex correlation analysis, and driving-factor zoning principles, were used to examine the characteristics of the spatiotemporal changes in evapotranspiration and to explore the driving mechanism of the changes in evapotranspiration. The results indicated that the range of fluctuations in the multiyear average evapotranspiration in the Aksu River Basin from 2001 to 2020 was between 481.58 and 772.37 mm/a, which showed the spatial distribution characteristics of being high in the west and central part of the basin, and low in the north and south of the basin. The positive correlation between evapotranspiration and precipitation was stronger, and the negative correlations with temperature and relative humidity were stronger. The change in evapotranspiration in cultivated land is mainly driven by precipitation and relative humidity × precipitation; for grassland, the main drivers were relative humidity and precipitation × relative humidity; for woodland, the main drivers were relative humidity and other climatic factors; and for other land types, the main drivers were other climatic factors.
Integrating Cost-Effective Measurements and CFD Modeling for Accurate Air Quality Assessment
Authors: Ioannidis Giannis , Tremper Paul , Li Chaofan , Riedel Till , Rapkos Nikolaos , Boikos Christos , Ntziachristos Leonidas
Published: September 2024

Assessing air quality in urban areas is vital for protecting public health, and low-cost sensor networks help quantify the population’s exposure to harmful pollutants effectively. This paper introduces an innovative method to calibrate air-quality sensor networks by combining CFD modeling with dependable AQ measurements. The developed CFD model is used to simulate traffic-related PM10 dispersion in a 1.6 × 2 km2 urban area. Hourly simulations are conducted, and the resulting concentrations are cross-validated against high-quality measurements. By offering detailed 3D information at a micro-scale, the CFD model enables the creation of concentration maps at sensor locations. Through regression analysis, relationships between low-cost sensor (LCS) readings and modeled outcomes are established and used for network calibration. The study demonstrates the methodology’s capability to provide aid to low-cost devices during a representative 24 h period. The precision of a CFD model can also guide optimal sensor placement based on prevailing meteorological and emission scenarios and refine existing networks for more accurate urban air quality representation. The usage of cost-effective air quality networks, high-quality monitoring stations, and high-resolution air quality modeling combines the strengths of both top-down and bottom-up approaches for air quality assessment. Therefore, the work demonstrated plays a significant role in providing reliable pollutant monitoring and supporting the assessment of environmental policies, aiming to address health issues related to urban air pollution.
Optimal Service Time Distribution for an M/G/1 Waiting Queue
Authors: Lefebvre Mario , Yaghoubi Roozbeh
Published: September 2024

Suppose that in an M/G/1 waiting queue, the server can choose between two service time distributions. We look for the choice that enables us to minimize the expected value of a cost criterion that takes into account the cost incurred by working faster and the time needed to empty the waiting line. The random final time is the first time there is no customer waiting for service. When the service times are exponential random variables, we can appeal to dynamic programming to obtain the optimal solution. In the general case, conditional probability is used. Particular problems in which the capacity of the system is finite are solved explicitly.
The Invariant Subspace Problem for Separable Hilbert Spaces
Authors: Khalil Roshdi , Yousef Abdelrahman , Alshanti Waseem Ghazi , Hammad Ma’mon Abu
Published: September 2024

In this paper, we prove that every bounded linear operator on a separable Hilbert space has a non-trivial invariant subspace. This answers the well-known invariant subspace problem.
Unit-Power Half-Normal Distribution Including Quantile Regression with Applications to Medical Data
Authors: Santoro Karol I. , Gómez Yolanda M. , Soto Darlin , Barranco-Chamorro Inmaculada
Published: September 2024

In this paper, we present the unit-power half-normal distribution, derived from the power half-normal distribution, for data analysis in the open unit interval. The statistical properties of the unit-power half-normal model are described in detail. Simulation studies are carried out to evaluate the performance of the parameter estimators. Additionally, we implement the quantile regression for this model, which is applied to two real healthcare data sets. Our findings suggest that the unit power half-normal distribution provides a robust and flexible alternative for existing models for proportion data.
Evaluating a Fe-Based Metallic Glass Powder as a Novel Negative Electrode Material for Applications in Ni-MH Batteries
Authors: Sotelo Oscar , Henao John , Poblano Carlos , Campillo Bernardo , Castañeda Erick , Flores Néstor , Molina Arturo , Martínez Horacio
Published: September 2024

Metallic glasses (MGs) are a type of multicomponent non-crystalline metallic alloys obtained by rapid cooling, which possess several physical, mechanical, and chemical advantages against their crystalline counterparts. In this work, an Fe-based MG is explored as a hydrogen storage material, especially, due to the evidence in previous studies about the capability of some amorphous metals to store hydrogen. The evaluation of an Fe-based MG as a novel negative electrode material for nickel/metal hydride (Ni-MH) batteries was carried out through cyclic voltammetry and galvanostatic charge–discharge tests. A conventional LaNi5 electrode was also evaluated for comparative purposes. The electrochemical results obtained by cyclic voltammetry showed the formation of three peaks, which are associated with the formation of Fe oxides/oxyhydroxides and hydroxides. Cycling charge/discharge tests revealed activation of the MG electrode. The highest discharge capacity value was 173.88 mAh/g, but a decay in its capacity was observed after 25 cycles, contrary to the LaNi5, which presents an increment of the discharge capacity for all the current density values evaluated, reached its value maximum at 183 mAh/g. Characterization analyses performed by X-ray diffraction, Scanning Electron Microscopy and Raman Spectroscopy revealed the presence of corrosion products and porosity on the surface of the Fe-based MG electrodes. Overall, the Fe-based MG composition is potentially able to work as a negative electrode material, but degradation and little information about storage mechanisms means that it requires further investigation.
Contextual Intelligence: An AI Approach to Manufacturing Skills’ Forecasting
Authors: Maphisa Xolani , Nkadimeng Mpho , Telukdarie Arnesh
Published: September 2024

The manufacturing industry is skill-intensive and plays a pivotal role in South Africa’s economy, reflecting the nation’s progress and development. The advent of technology has initiated a transformative era within the manufacturing sector. Workforce skills are at the heart of ensuring the sustained growth of the industry. This study delves into the skill-related aspects of the occupational landscape of the South African manufacturing sector, with a particular focus on two important manufacturing sectors: the food and beverage manufacturing (FoodBev) sector and the chemical manufacturing (CHIETA) sector. Leveraging the forecasting prowess of Autoregressive Integrated Moving Average (ARIMA), this paper outlines a sectorial occupational forecasting modeling exercise to reveal which job roles are poised for expansion and which are expected to decline. The approach predicted future skills’ demand 80% accuracy for 473 out of 713 (66%) occupations for FoodBev and 474 out of 522 (91%) for CHIETA. These insights are invaluable for industry stakeholders and educational institutions, providing guidance to support the sector’s growth in an era marked by technological advancement.
Analysis of Metabolic Profiles and Antioxidant Activity of Chinese Cordyceps, Ophiocordyceps sinensis, and Paecilomyces hepiali Based on Untargeted Metabolomics
Authors: He Min , Tang Chu-Yu , Wang Tao , Xiao Meng-Jun , Li Yu-Ling , Li Xiu-Zhang
Published: September 2024

Chinese cordyceps (GL) is a traditional medicinal fungus, with Ophiocordyceps sinensis (O. sinensis, BL) and Paecilomyces hepiali (P. hepiali, JSB) being fungi isolated from wild Chinese cordyceps. These three species share similar chemical composition and pharmacological effects. Existing studies have primarily compared the metabolites of Chinese cordyceps and O. sinensis, overlooking the assessment of antioxidant capacity in Chinese cordyceps, P. hepiali, and O. sinensis. In this study, LC-MS/MS was employed to analyze metabolites in GL, JSB, and BL. Utilizing principal component analysis (PCA), supervised orthogonal partial least squares discriminant analysis (OPLS-DA), and hierarchical cluster analysis (HCA), it was observed that the majority of differential metabolites (DMs) primarily accumulated in organic acids and derivatives, lipids and lipid-like molecules, and organoheterocyclic compounds. Antioxidant activity analysis indicated that GL exhibited the higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability (DPPH•, scavenging rate is 81.87 ± 0.97%), hydroxyl free radical scavenging capacity (•OH, scavenging rate is 98.10 ± 0.60%), and superoxide anion radical scavenging capacity (O2•−, scavenging rate is 69.74 ± 4.36%), while JSB demonstrated the higher FRAP total antioxidant capacity of 8.26 μmol Trolox/g (p < 0.05). Correlation analysis revealed a positive correlation between DMs (fatty acyls and amino acids) and DPPH•, FRAP, •OH, and O2•− (p < 0.05). Additionally, glycerophospholipid DMs were found to be positively correlated with FRAP (p < 0.05). Through KEGG pathway analysis, it was determined that the accumulation of DMs in pathways such as cutin, suberine and wax biosynthesis has a higher impact on influencing the antioxidant activity of the samples. These results shed light on the antioxidant capacity and metabolic characteristics of Chinese cordyceps and its substitutes and offer valuable insights into how different DMs impact the strength of antioxidant activity, aiding in the advancement and application of Chinese cordyceps and its substitutes.
Morphological and Biophysical Study of S100A9 Protein Fibrils by Atomic Force Microscopy Imaging and Nanomechanical Analysis
Authors: Carapeto Ana P. , Marcuello Carlos , Faísca Patrícia F. N. , Rodrigues Mário S.
Published: September 2024

Atomic force microscopy (AFM) imaging enables the visualization of protein molecules with high resolution, providing insights into their shape, size, and surface topography. Here, we use AFM to study the aggregation process of protein S100A9 in physiological conditions, in the presence of calcium at a molar ratio 4Ca2+:S100A9. We find that S100A9 readily assembles into a worm-like fibril, with a period dimension along the fibril axis of 11.5 nm. The fibril’s chain length extends up to 136 periods after an incubation time of 144 h. At room temperature, the fibril’s bending stiffness was found to be 2.95×10−28 Nm2, indicating that the fibrils are relatively flexible. Additionally, the values obtained for the Young’s modulus (Ex=6.96×105 Pa and Ey=3.37×105 Pa) are four orders of magnitude lower than those typically reported for canonical amyloid fibrils. Our findings suggest that, under the investigated conditions, a distinct aggregation mechanism may be in place in the presence of calcium. Therefore, the findings reported here could have implications for the field of biomedicine, particularly with regard to Alzheimer’s disease.
Mitochondrial Dysfunction in Glycogen Storage Disorders (GSDs)
Authors: Mishra Kumudesh , Kakhlon Or
Published: September 2024

Glycogen storage disorders (GSDs) are a group of inherited metabolic disorders characterized by defects in enzymes involved in glycogen metabolism. Deficiencies in enzymes responsible for glycogen breakdown and synthesis can impair mitochondrial function. For instance, in GSD type II (Pompe disease), acid alpha-glucosidase deficiency leads to lysosomal glycogen accumulation, which secondarily impacts mitochondrial function through dysfunctional mitophagy, which disrupts mitochondrial quality control, generating oxidative stress. In GSD type III (Cori disease), the lack of the debranching enzyme causes glycogen accumulation and affects mitochondrial dynamics and biogenesis by disrupting the integrity of muscle fibers. Malfunctional glycogen metabolism can disrupt various cascades, thus causing mitochondrial and cell metabolic dysfunction through various mechanisms. These dysfunctions include altered mitochondrial morphology, impaired oxidative phosphorylation, increased production of reactive oxygen species (ROS), and defective mitophagy. The oxidative burden typical of GSDs compromises mitochondrial integrity and exacerbates the metabolic derangements observed in GSDs. The intertwining of mitochondrial dysfunction and GSDs underscores the complexity of these disorders and has significant clinical implications. GSD patients often present with multisystem manifestations, including hepatomegaly, hypoglycemia, and muscle weakness, which can be exacerbated by mitochondrial impairment. Moreover, mitochondrial dysfunction may contribute to the progression of GSD-related complications, such as cardiomyopathy and neurocognitive deficits. Targeting mitochondrial dysfunction thus represents a promising therapeutic avenue in GSDs. Potential strategies include antioxidants to mitigate oxidative stress, compounds that enhance mitochondrial biogenesis, and gene therapy to correct the underlying mitochondrial enzyme deficiencies. Mitochondrial dysfunction plays a critical role in the pathophysiology of GSDs. Recognizing and addressing this aspect can lead to more comprehensive and effective treatments, improving the quality of life of GSD patients. This review aims to elaborate on the intricate relationship between mitochondrial dysfunction and various types of GSDs. The review presents challenges and treatment options for several GSDs.
Natural Compounds for the Treatment of Acute Pancreatitis: Novel Anti-Inflammatory Therapies
Authors: Jiang Wenkai , Li Xiao , Zhang Yi , Zhou Wence
Published: September 2024

Acute pancreatitis remains a serious public health problem, and the burden of acute pancreatitis is increasing. With significant morbidity and serious complications, appropriate and effective therapies are critical. Great progress has been made in understanding the pathophysiology of acute pancreatitis over the past two decades. However, specific drugs targeting key molecules and pathways involved in acute pancreatitis still require further study. Natural compounds extracted from plants have a variety of biological activities and can inhibit inflammation and oxidative stress in acute pancreatitis by blocking several signaling pathways, such as the nuclear factor kappa-B and mitogen-activated protein kinase pathways. In this article, we review the therapeutic effects of various types of phytochemicals on acute pancreatitis and discuss the mechanism of action of these natural compounds in acute pancreatitis, aiming to provide clearer insights into the treatment of acute pancreatitis.
Neuroimmune Crossroads: The Interplay of the Enteric Nervous System and Intestinal Macrophages in Gut Homeostasis and Disease
Authors: Lou Meng , Heuckeroth Robert O. , Tjaden Naomi E. Butler
Published: September 2024

A defining unique characteristic of the gut immune system is its ability to respond effectively to foreign pathogens while mitigating unnecessary inflammation. Intestinal macrophages serve as the cornerstone of this balancing act, acting uniquely as both the sword and shield in the gut microenvironment. The GI tract is densely innervated by the enteric nervous system (ENS), the intrinsic nervous system of the gut. Recent advances in sequencing technology have increasingly suggested neuroimmune crosstalk as a critical component for homeostasis both within the gut and in other tissues. Here, we systematically review the ENS–macrophage axis. We focus on the pertinent molecules produced by the ENS, spotlight the mechanistic contributions of intestinal macrophages to gut homeostasis and inflammation, and discuss both existing and potential strategies that intestinal macrophages use to integrate signals from the ENS. This review aims to elucidate the complex molecular basis governing ENS–macrophage signaling, highlighting their cooperative roles in sustaining intestinal health and immune equilibrium.
New BDNF and NT-3 Cyclic Mimetics Concur with Copper to Activate Trophic Signaling Pathways as Potential Molecular Entities to Protect Old Brains from Neurodegeneration
Authors: Magrì Antonio , Tomasello Barbara , Naletova Irina , Tabbì Giovanni , Cairns Warren R. L. , Greco Valentina , Sciuto Sebastiano , La Mendola Diego , Rizzarelli Enrico
Published: September 2024

A low level of Neurotrophins (NTs), their Tyrosine Kinase Receptors (Trks), Vascular Endothelial Growth Factors (VEGFs) and their receptors, mainly VEGFR1 and VEGFR2, characterizes AD brains. The use of NTs and VEGFs as drugs presents different issues due to their low permeability of the blood−brain barrier, the poor pharmacokinetic profile, and the relevant side effects. To overcome these issues, different functional and structural NT mimics have been employed. Being aware that the N-terminus domain as the key domain of NTs for the binding selectivity and activation of Trks and the need to avoid or delay proteolysis, we herein report on the mimicking ability of two cyclic peptide encompassing the N-terminus of Brain Derived Growth Factor (BDNF), (c-[HSDPARRGELSV-]), cBDNF(1-12) and of Neurotrophin3 (NT3), (c-[YAEHKSHRGEYSV-]), cNT3(1-13). The two cyclic peptide features were characterized by a combined thermodynamic and spectroscopic approach (potentiometry, NMR, UV-vis and CD) that was extended to their copper(II) ion complexes. SH-SY5Y cell assays show that the Cu2+ present at the sub-micromolar level in the complete culture media affects the treatments with the two peptides. cBDNF(1-12) and cNT3(1-13) act as ionophores, induce neuronal differentiation and promote Trks and CREB phosphorylation in a copper dependent manner. Consistently, both peptide and Cu2+ stimulate BDNF and VEGF expression as well as VEGF release; cBDNF(1-12) and cNT3(1-13) induce the expression of Trks and VEGFRs.
A Triple Mystery of Insidious Organ Failure: Are the Lung, Kidney and Brain All Damaged by the Ageing Pulse?
Authors: Stone Jonathan , Robinson Stephen R. , Mitrofanis John , Johnstone Daniel M.
Published: September 2024

This review explores the hypothesis that dementia in several forms, chronic kidney disease and idiopathic pulmonary fibrosis have a common cause in pulse-induced capillary haemorrhage. All three conditions are age-related and characterised by insidious onset, uncertainty about their cause, exacerbation by hypertension, resistance to treatment and the relentlessness of their progression. We argue that the three conditions are the clinical outcomes of damage caused by pulse-induced haemorrhage from capillaries. The damage, first detectable in mid-life, creates first mild and then severe symptoms of cognitive, renal and pulmonary dysfunction. We also review evidence that in all three organs there has developed, by young adulthood, a reserve of tissue that enables them to function well, despite the ‘heartbeat by heartbeat’ damage that accumulates from early mid-life; and that it is when that reserve is exhausted, typically in late age, that symptoms of organ failure emerge and progress. If this common cause can be established, a step will have been taken towards the understanding, treatment and delay of three conditions that have their beginnings in every individual and that, in those who survive other causes of death, become lethal in late age.
Infliximab in Inflammatory Bowel Disease: Leveraging Physiologically Based Pharmacokinetic Modeling in the Clinical Context
Authors: Petric Zvonimir , Gonçalves João , Paixão Paulo
Published: September 2024

In this study, a physiologically based pharmacokinetic (PBPK) modeling framework was employed to explore infliximab exposure following intravenous (5 mg/kg) and subcutaneous administration (encompassing the approved 120 mg flat-fixed dose as a switching option) in virtual adult and pediatric patients with inflammatory bowel disease (IBD). The PBPK model and corresponding simulations were conducted using the PK-Sim® software platform. The PBPK simulation indicated that a 120 mg subcutaneous flat-fixed dose might not be optimal for heavier adults with IBD, suggesting the need for infliximab dose escalation. For an older virtual pediatric patient (14 years old), subcutaneous administration of a 120 mg flat-fixed dose appears to be a feasible IBD treatment option. In the final exploration scenario, the model was extended to predict hypothetical subcutaneous infliximab doses in a virtual pediatric population (6–18 years old), stratified into three weight bands (20–30 kg, 30–45 kg, and 45–70 kg), that would yield post-switch trough concentrations of infliximab comparable to those seen in adults with the 120 mg flat-fixed subcutaneous dose. The PBPK-model-informed dose suggestions were 40 mg for the 20–30 kg band, 80 mg for the 30–45 kg band, and 120 mg for the 45–70 kg band. As demonstrated in this paper, the PBPK modeling framework can serve as a versatile tool in clinical pharmacology to investigate various clinical scenarios, such as exploring alternative dosing regimens and routes of administration, ultimately advancing IBD treatment across diverse (sub)populations of clinical interest.
Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms
Authors: Speranza Luisa , Filiz Kardelen Dalim , Lippiello Pellegrino , Ferraro Maria Grazia , Pascarella Silvia , Miniaci Maria Concetta , Volpicelli Floriana
Published: September 2024

Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes in brain structure and function, impacting areas involved in emotion regulation, cognition, and stress response. Consequently, individuals exposed to high levels of ELS are at an increased risk for mental health disorders like depression, anxiety, and post-traumatic stress disorders, as well as physical health issues, including metabolic disorders, cardiovascular disease, and cancer. This review explores the biological and psychological consequences of early-life adversity paradigms in rodents, such as maternal separation or deprivation and limited bedding or nesting. The study of these experimental models have revealed that the organism’s response to ELS is complex, involving genetic and epigenetic mechanisms, and is associated with the dysregulation of physiological systems like the nervous, neuroendocrine, and immune systems, in a sex-dependent fashion. Understanding the impact of ELS is crucial for developing effective interventions and preventive strategies in humans exposed to stressful or traumatic experiences in childhood.
Effects of Polyunsaturated Fatty Acid/Saturated Fatty Acid Ratio and Different Amounts of Monounsaturated Fatty Acids on Adipogenesis in 3T3-L1 Cells
Authors: Lim Sim Yee , Chien Yi-Wen
Published: September 2024

(1) Background: Adipose tissue serves as a central repository for energy storage and is an endocrine organ capable of secreting various adipokines, including leptin and adiponectin. These adipokines exert profound influences on diverse physiological processes such as insulin sensitivity, appetite regulation, lipid metabolism, energy homeostasis, and body weight. Given the integral role of adipose tissue in metabolic regulation, it is imperative to investigate the effects of varying proportions and types of dietary fats on adipocyte function. In addition, our previous study showed that P/S = 5 and MUFA = 60% appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in β-oxidation. Therefore, the objective of this study was to explore the effects of a polyunsaturated fatty acid (PUFA) to saturated fatty acid (SFA) ratio of 5 and varying levels of monounsaturated fatty acids (MUFA = 30% or 60%) on lipogenesis. (2) Methods: We cultured 3T3-L1 mouse embryo fibroblasts in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% bovine calf serum until confluent. Varying ratios of palmitic acid (PA), oleic acid (OA), and linoleic acid (LA) were first bound with bovine serum albumin (BSA) before being applied to 3T3-L1 adipocytes in low doses and in high doses. (3) Results: Low doses of P/S ratio = 5, MUFA = 60% (M60) fatty acids decreased the accumulation of triglycerides in mature adipocytes by decreasing the mRNA expression of adipogenic factors, such as peroxisome proliferator-activated receptors (PPARs), lipoprotein lipase (LPL), and glucose transporter-4 (GLUT-4), while increasing lipolytic enzyme (hormone-sensitive lipase, HSL) expression when compared to high doses of P/S ratio = 5, MUFA = 60% (M60), low and high doses of P/S ratio = 5, MUFA = 30% (M30). Furthermore, the treatment of M60 in low doses also decreased the secretion of leptin and increased the secretion of adiponectin in adipocytes. (4) Conclusions: The composition of P/S = 5, MUFA = 60% fatty acid in low doses appeared to result in anti-adipogenic effects on 3T3-L1 adipocytes due to the down-regulation of adipogenic effects and the transcription factor.
Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
Authors: Nakamura Ronan , Ciranna Nicolás S. , Fernández Juan C. , Peláez Rafael , Pérez-Sala Álvaro , Bobadilla Miriam , López-Costa Juan J. , Loidl César F. , Martínez Alfredo , Rey-Funes Manuel
Published: September 2024

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.
Comparison of the Effectiveness of Vedolizumab and Ustekinumab in Patients with Ulcerative Colitis: A Real-World Retrospective Study
Authors: Nomura Kei , Shibuya Tomoyoshi , Odakura Rina , Haraikawa Mayuko , Ishino Hirotaka , Orikasa Masayuki , Omori Masashi , Koma Masao , Ito Kentaro , Maruyama Takafumi , Nomura Osamu , Ishikawa Dai , Hojo Mariko , Nagahara Akihito
Published: September 2024

Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine. Data on the comparative effectiveness of biological therapies such as vedolizumab (VDZ) and ustekinumab (UST) remain limited. This retrospective study compared the effectiveness and safety of VDZ and UST in UC patients. Between November 2018 and November 2023, 106 patients were included: 64 received VDZ and 42 received UST. Bio-failure was significantly higher (p = 0.005) in the UST group versus the VDZ group. The remission rates at 6, 22, and 54 weeks in VDZ group were 51.6%, 61.3%, and 66.7%. The remission rates at 8, 24, and 56 weeks in the UST group were 66.7%, 65.0%, and 66.7%, respectively. Both treatments were comparable in inducing and maintaining clinical remission over 54–56 weeks, with no significant differences observed in the Lichtiger clinical activity index. Subgroup analyses highlighted the potential short-term effectiveness of UST among cases of bio-failure and a white blood cell level ≥ 9000/µL. Safety profiles were generally favorable, with no significant adverse events. Usutekinumab demonstrated effectiveness as a salvage therapy in patients who failed VDZ. Despite the increased disease severity in the UST group compared to the VDZ group, both groups demonstrated similar remission rates, suggesting UST shows significant efficacy even in moderate to severe UC.
Pittsburgh Sleep Quality Index (PSQI) Changes in Virologically Suppressed People Living with HIVSwitching to Long-Acting Cabotegravir and Rilpivirine
Authors: De Gennaro Nicolò , Poliseno Mariacristina , Dargenio Angelo , Balena Flavia , Fiordelisi Deborah , Spada Vito , Romita Greta , Guido Giacomo , Di Gennaro Francesco , Bruno Giuseppe , Purgatorio Mariantonietta , Buccoliero Giovanni Battista , Saracino Annalisa
Published: September 2024

Background: Limited evidence is available about sleep quality changes associated with the use of Cabotegravir (CAB), a new, long-acting (LA) antiretroviral (ARV) drug belonging to the class of Integrase Strand Transfer Inhibitors (INSTIs). Methods: Pittsburgh Sleep Quality Index (PSQI) was calculated in 53 people living with HIV (PLWH) under the care of the outpatient services of two Italian Infectious Diseases Centers in Apuliabefore (M0) and seven months after (M7) the switch to LA CAB. Global scores and relative subitems were compared using paired sample tests. The same analysis was repeated in subgroups of PLWH switching from INSTIs-, Dolutegravir-(DTG), and Bictegravir (BIC)-based regimens. Results: A significant reduction was reported in global mean (±StandardDeviation, SD) PSQI at M7 compared to M0 (4 (±3) vs. 3 (±2), p = 0.01), particularly in the areas of sleep latency and sleep disturbances. The improvement was also significant in PLWH already on INSTIs- (from median 3 to 2 points, p = 0.02) and DTG-based (from median 4 to 2, p = 0.01) ARV regimens, but not among those who switched from BIC-based regimens. Conclusions: PLWH reported improved sleep quality after switching from ARV treatment to LA CAB. Further studies are needed to give deeper insights into this phenomenon.