bluuebunny/crossref_metadata_2025 huggingface dataset:
Hawthorn Proanthocyanidin Extract Inhibits Colorectal Carcinoma Metastasis by Targeting the Epithelial-Mesenchymal Transition Process and Wnt/β-Catenin Signaling Pathway
Authors: Wang Ziwei , Sun Yasai , Wu Mengying , Zhou Liangfu , Zheng Yu , Ren Ting , Li Meijiao , Zhao Wen
Published: April 2024

Colorectal carcinoma (CRC) is a major global health concern, with cancer metastasis being the main cause of patient mortality, and current CRC treatments are challenged by drug resistance. Although natural compounds, especially in foods like hawthorn proanthocyanidin extract (HPOE), have good anticancer activity, their effects on CRC metastasis remain unknown. Therefore, our objective was to investigate the impact and potential mechanisms of HPOE on the movement and infiltration of cells in the HCT116 CRC cells. Firstly, scratch-healing experiments confirmed the anti-migratory and anti-invasive capabilities of HPOE. Then, network pharmacology identified 16 possible targets, including MMP-9. Subsequently, RT-qPCR and Western blotting experiments confirmed that HPOE downregulated epithelial-mesenchymal transition-related factors (N-cadherin and MMP-9) and inhibited Wnt/β-catenin pathway activation. Finally, these results were experimentally validated using the Wnt pathway activator Licl and inhibitor XAV939. It was confirmed that HPOE had a certain inhibitory effect on the activation of the Wnt signaling pathway caused by the activator Licl and could enhance the inhibitory effect of the inhibitor XAV939. Our findings provide a basis for developing functional foods or dietary supplements, especially positioning HPOE as a functional food raw material for adjuvant treatment of CRC, given its ability to inhibit metastasis through the Wnt/β-catenin pathway.
Preparation, Characterization and Application of Active Food Packaging Films Based on Sodium Alginate and Twelve Varieties of Mandarin Peel Powder
Authors: Yun Dawei , Liu Jun
Published: April 2024

The industrial processing of mandarin fruits yields a large amount of peel waste, resulting in economic losses and environmental pollution. The peels of mandarin fruits are a good source of biomass and active substances that can be used to produce food packaging systems. In this study, active food packaging films were prepared based on sodium alginate and twelve varieties of mandarin peel powder. The structures, properties, and corn oil packaging performance of the films were compared. Results showed that the twelve varieties of mandarin peel powder differed in pectin, lipid, protein, crude fiber, and total phenol contents. The prepared films all exhibited a yellow color, 117.73–152.45 μm thickness, 16.39–23.62% moisture content, 26.03–90.75° water contact angle, 5.38–8.31 × 10−11 g m−1 s−1 Pa−1 water vapor permeability, 5.26–12.91 × 10−20 m2 s−1 Pa−1 oxygen permeability, 4.87–7.90 MPa tensile strength, and 13.37–24.62% elongation at break. Notably, the films containing mandarin peel powder with high pectin and lipid contents showed high moisture/oxygen barrier ability and mechanical properties. The films containing mandarin peel powder with high total phenol content exhibited high antioxidant- and antimicrobial-releasing abilities and good performance in delaying corn oil oxidation. Overall, the results suggested that the films have good application potential in active food packaging.
Soy-Based High-Protein Spheric Foods with the Appearance of Familiar Sugary Snacks
Authors: Yano Hiroyuki , Tanaka Rika , Fu Wei
Published: April 2024

Excessive consumption of sugary foods increases the likelihood of obesity, as well as the preventable risk of lifestyle illnesses such as diabetes and cardiovascular diseases. Frequent intake of sweet snacks is considered to increase the risk of overweight/obesity in industrial nations. However, we cannot stop snacking against our better judgment. Therefore, in this study, we sought to develop high-protein, low-carb “mock snacks” to satisfy snack lovers’ appetites and nutrition. Soy protein-based, ball-shaped food products with 57.7% (w/w) protein and 3.6% sugar have been developed. The addition of canola oil made them melty in the mouth without sacrificing their crispiness. Moreover, evaluation of the surface topography of the “soy balls” by 3D laser scanning demonstrated their high degree of sphericity. Conclusively, the snacks developed here may be one of the healthy alternatives for the current sugary ones.
Preparation and Characterization of a Hypoglycemic Complex of Gallic Acid–Antarctic Krill Polypeptide Based on Polylactic Acid–Hydroxyacetic Acid (PLGA) and High-Pressure Microjet Microencapsulation
Authors: Li Mengjie , Chen Puyu , Lin Yichen , Miao Song , Bao Hairong
Published: April 2024

Gallic acid–Antarctic krill peptides (GA-AKP) nanocapsules (GA-AKP-Ns) were prepared using a dual delivery system with complex emulsion as the technical method, a high-pressure microjet as the technical means, polylactic acid–hydroxyacetic acid (PLGA) as the drug delivery vehicle, and GA-AKP as the raw material for delivery. This study aimed to investigate the effects of microjet treatment and the concentration of PLGA on the physicochemical properties and stability of the emulsion. Under optimal conditions, the physicochemical properties and hypoglycemic function of nano-microcapsules prepared after lyophilization by the solvent evaporation method were analyzed. Through the microjet treatment, the particle size of the emulsion was reduced, the stability of the emulsion was improved, and the encapsulation rate of GA-AKP was increased. The PLGA at low concentrations decreased the particle size of the emulsion, while PLGA at high concentrations enhanced the encapsulation efficiency of the emulsion. Additionally, favorable results were obtained for emulsion preparation through high-pressure microjet treatment. After three treatment cycles with a PLGA concentration of 20 mg/mL and a microjet pressure of 150 MPa (manometric pressure), the emulsion displayed the smallest particle size (285.1 ± 3.0 nm), the highest encapsulation rates of GA (71.5%) and AKP (85.2%), and optimal physical stability. GA-AKP was uniformly embedded in capsules, which can be slowly released in in vitro environments, and effectively inhibited α-amylase, α-glucosidase, and DPP-IV at different storage temperatures. This study demonstrated that PLGA as a carrier combined with microjet technology can produce excellent microcapsules, especially nano-microcapsules, and these microcapsules effectively improve the bioavailability and effectiveness of bioactive ingredients.
Identification of Key Parameters Inducing Microbial Modulation during Backslopped Kombucha Fermentation
Authors: Daval Claire , Tran Thierry , Verdier François , Martin Antoine , Alexandre Hervé , Grandvalet Cosette , Tourdot-Maréchal Raphaëlle
Published: April 2024

The aim of this study was to assess the impact of production parameters on the reproducibility of kombucha fermentation over several production cycles based on backslopping. Six conditions with varying oxygen accessibility (specific interface surface) and initial acidity (through the inoculation rate) of the cultures were carried out and compared to an original kombucha consortium and a synthetic consortium assembled from yeasts and bacteria isolated from the original culture. Output parameters monitored were microbial populations, biofilm weight, key physico-chemical parameters and metabolites. Results highlighted the existence of phases in microbial dynamics as backslopping cycles progressed. The transitions between phases occurred faster for the synthetic consortium compared to the original kombucha. This led to microbial dynamics and fermentative kinetics that were reproducible over several cycles but that could also deviate and shift abruptly to different behaviors. These changes were mainly induced by an increase in the Saccharomyces cerevisiae population, associated with an intensification of sucrose hydrolysis, sugar consumption and an increase in ethanol content, without any significant acceleration in the rate of acidification. The study suggests that the reproducibility of kombucha fermentations relies on high biodiversity to slow down the modulations of microbial dynamics induced by the sustained rhythm of backslopping cycles.
Heavy Metal Removal from Wastewater Using Poly(Gamma-Glutamic Acid)-Based Hydrogel
Authors: Chen Fujie , Zhao Yanbin , Zhao Hang , Zhou Xuan , Liu Xiuying
Published: April 2024

The removal of toxic heavy metal ions from wastewater is of great significance in the protection of the environment and human health. Poly(gamma-glutamic acid) (PGA) is a non-toxic, biodegradable, and highly water-soluble polymer possessing carboxyl and imino functional groups. Herein, water-insoluble PGA-based hydrogels were prepared, characterized, and investigated as heavy metal adsorbents. The prepared hydrogels were recyclable and exhibited good adsorption effects on heavy metal ions including Cu2+, Cr6+, and Zn2+. The effects of adsorption parameters including temperature, solution pH, initial concentration of metal ions, and contact time on the adsorption capacity of the hydrogel for Cu2+ were investigated. The adsorption was a spontaneous and exothermic process. The process followed the pseudo-first-order kinetic model and Langmuir isotherm model, implying a physical and monolayer adsorption. The adsorption mechanisms investigation exhibited that Cu2+ adsorbed on the hydrogel via electrostatic interactions with anionic carboxylate groups of PGA in addition to the coordination interactions with the –NH groups. Importantly, the PGA hydrogel exhibited good reusability and the adsorption capability for Cu2+ remained high after five consecutive cycles. The properties of PGA hydrogel make it a potential candidate material for heavy metal ion removal in wastewater treatment.
Lifestyle Factors Influencing Metabolic Syndrome after Adjusting for Socioeconomic Status and Female Reproductive Health Indicators: A National Representative Survey in Korean Pre- and Postmenopausal Women
Authors: Hong Eunyoung , Kang Youngmi
Published: April 2024

Metabolic syndrome (MetS) is increasing markedly among postmenopausal women. Although studies suggest multiple risk factors for its development, few have investigated changes in socioeconomic status (SES), female reproductive health indicators (menarche age, experience of pregnancy, delivery, breastfeeding, and postmenopausal status), and lifestyle factors. This study investigated lifestyle factors affecting MetS prevalence among pre- and post-menopausal women after adjusting for SES and female reproductive health indicators. Data from the Korea National Health and Nutrition Examination Survey VII (2016–2018) on 2856 pre- and postmenopausal women aged 40–59 years were analyzed. Differences in SES (e.g., age, education, and household income), female reproductive health indicators (e.g., age of menarche and menopause), and lifestyle (e.g., total calorie intake, fats, and proteins, percentage of energy from carbohydrates, fats, and proteins, smoking, physical activity, and obesity) between MetS and non-MetS groups were calculated by performing χ2 or t-tests. Consequently, current smoking, physical inactivity, overweight, and obesity were significantly associated with increased MetS after adjusting for SES and female reproductive health indicators using logistic regression analysis. Hence, health policies and programs focusing on modifiable MetS risk factors–encouraging healthy eating habits, smoking cessation, and regular exercise—must be formulated to prevent the development of MetS in pre- and postmenopausal women.
Xylem Hydraulic Conductance Role in Kiwifruit Decline Syndrome Occurrence
Authors: Mandalà Claudio , Monaco Stefano , Nari Luca , Morone Chiara , Palazzi Francesco , Bencresciuto Grazia Federica , Bardi Laura
Published: April 2024

Kiwifruit decline syndrome (KiDS) has affected kiwifruit orchards for more than ten years in the Mediterranean area, severely compromising productivity and causing extensive uprooting. The affected plants go through an irreversible and fast wilting process. The problem has not been solved yet, and a single cause has not been identified. In this work, we carried out a survey on ten five-year-old healthy kiwifruit cv. Hayward plants cultivated in an area strongly affected by KiDS and characterised by a rising temperature and vapor pressure deficit (VPD). Five plants were located in a KiDS-affected orchard. Our goal was to assess the hydraulic conductance of asymptomatic plants in a KiDS-affected area where rising climate change stress is underway. Our hypothesis was that a rising temperature and VPD could impair xylem functionality, leading the plants to develop strategies of tolerance, such as vessel narrowing, or stress symptoms, such as cavitation or implosion, inducing a higher risk of KiDS onset. Hydraulic conductance was investigated using a physiological and morphological approach to detect trunk sap flow, trunk growth and daily diameter variations, leaf gas exchanges and temperature, stem water potential, and the root xylem vessel diameter and vulnerability to cavitation. A strong xylem vessel narrowing was observed in all plants, with the highest frequency in the 30–45 µm diameter class, which is an indicator of long-term adaptation to a rising VPD. In some plants, cavitation and implosion were also observed, which are indicative of a short-term stress response; this behaviour was detected in the plants in the KiDS-affected orchard, where a high leaf temperature (>39 °C), low stomatal conductance (<0.20 mol H2O m−2 s−1) and transpiration (<3 mmol H2O m−2 s−1), low stem water potential (<−1 MPa), high vulnerability to cavitation (3.7 μm mm−2), low trunk sap flow and high daily stem diameter variation confirmed the water stress status. The concurrence of climate stress and agronomic management in predisposing conditions favourable to KiDS onset are discussed, evidencing the role of soil preparation, propagation material and previous crop.
Integrated Exploitation of Rainwater and Groundwater: A Strategy for Water Self-Sufficiency in Ca Mau Province of the Mekong Delta
Authors: Vinh Dang Hoa , Tran Dung Duc , Cham Dao Dinh , Hang Phan Thi Thanh , Man Duong Ba , Mon Danh , Hai Tung Luu , Kiem Le Van , Nguyen Thien Duc , Tuyen Duong Thi Ngoc
Published: April 2024

Groundwater sources have been exploited excessively for numerous purposes worldwide, leading to increasingly severe depletion. However, the replenishment of groundwater sources has not usually been a focus in economically and socially underdeveloped countries and regions. In coastal provinces of the Vietnamese Mekong Delta (VMD), rural areas are facing difficulties in accessing fresh water due to shortages from the water supply plant and excessive use of groundwater, highlighting an urgent need for sustainable development solutions. Our study first conducted interviews with 200 households in Ca Mau Province of the VMD to identify the current situation and the challenges and obstacles of rainwater harvesting and to find sustainable and proactive solutions. We then analyzed daily rainfall data from 10 meteorological stations to construct four scenarios of the water balance method: (i) potential rainwater harvesting based on existing roof area; (ii) optimal scale of storage tank and catchments for different levels of water usage; (iii) tank scale utilizing rainwater entirely during the rainy season and basic needs during the dry season; and (iv) integrated water supply between rain and groundwater. The results showed that using rainwater entirely for domestic water supply requires large storage tank capacities, making these scenarios difficult to achieve in the near future. Our research introduces a novel integrated water supply approach to storing rain and groundwater that has demonstrated high effectiveness and sustainability. With existing tank capacities (0.8 m3 per person), rainwater could only meet over 48% (14 m3 per year) of the water demand while requiring 14.8 m3 of additional groundwater extraction. With a tank capacity of 2.4 m3 per person, ensuring rainwater harvesting meets basic demand, harvested rainwater could satisfy 64% of the demand, with artificial groundwater supplementation exceeding 1.79 times the required extraction, while excess rainwater discharge into the environment would be minimal. Our research results not only provide potential solutions for rainwater and groundwater collection to supplement sustainable domestic water sources for Ca Mau but also serve as an example for similar regions globally.
Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca2+-Dependent Activation of the Calcium-Gated Potassium SK4 Channel
Authors: Segura Émilie , Zhao Juan , Broszczak Marlena , Audet Frédéric , Sauvé Rémy , Parent Lucie
Published: April 2024

Ca2+ binding to the ubiquitous Ca2+ sensing protein calmodulin (CaM) activates the intermediate conductance Ca2+-activated SK4 channel. Potential hydrophilic pockets for CaM binding have been identified at the intracellular HA and HB helices in the C-terminal of SK4 from the three published cryo-EM structures of SK4. Single charge reversal substitutions at either site, significantly weakened the pull-down of SK4 by CaM wild-type (CaM), and decreased the TRAM-34 sensitive outward K+ current densities in native HEK293T cells when compared with SK4 WT measured under the same conditions. Only the doubly substituted SK4 R352D/R355D (HB helix) obliterated the CaM-mediated pull-down and thwarted outward K+ currents. However, overexpression of CaM E84K/E87K, which had been predicted to face the arginine doublet, restored the CaM-mediated pull-down of SK4 R352D/R355D and normalized its whole-cell current density. Virtual analysis of the putative salt bridges supports a unique role for the positively charged arginine doublet at the HB helix into anchoring the interaction with the negatively charged CaM glutamate 84 and 87 CaM. Our findings underscore the unique contribution of electrostatic interactions in carrying CaM binding onto SK4 and support the role of the C-terminal HB helix to the Ca2+-dependent gating process.
Precision Medicine Approaches in Acute Myeloid Leukemia with Adverse Genetics
Authors: Santoro Nicole , Salutari Prassede , Di Ianni Mauro , Marra Andrea
Published: April 2024

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances in the field focusing on the contribution of molecular drivers of leukemia biogenesis and evolution and on the alterations of the immune system that can be exploited with immune-based therapeutic strategies. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes of patients affected by AML with adverse genetics.
Geniposide and Harpagoside Functionalized Cerium Oxide Nanoparticles as a Potential Neuroprotective
Authors: Pérez Gutiérrez Rosa Martha , Rodríguez-Serrano Luis Miguel , Laguna-Chimal José Fidel , de la Luz Corea Mónica , Paredes Carrera Silvia Patricia , Téllez Gomez Julio
Published: April 2024

Alzheimer’s disease is associated with protein aggregation, oxidative stress, and the role of acetylcholinesterase in the pathology of the disease. Previous investigations have demonstrated that geniposide and harpagoside protect the brain neurons, and cerium nanoparticles (CeO2 NPs) have potent redox and antioxidant properties. Thus, the effect of nanoparticles of Ce NPs and geniposide and harpagoside (GH/CeO2 NPs) on ameliorating AD pathogenesis was established on AlCl3-induced AD in mice and an aggregation proteins test in vitro. Findings of spectroscopy analysis have revealed that GH/CeO2 NPs are highly stable, nano-size, spherical in shape, amorphous nature, and a total encapsulation of GH in cerium. Treatments with CeO2 NPs, GH/CeO2 NPs, and donepezil used as positive control inhibit fibril formation and protein aggregation, protect structural modifications in the BSA-ribose system, have the ability to counteract Tau protein aggregation and amyloid-β1–42 aggregation under fibrillation condition, and are able to inhibit AChE and BuChE. While the GH/CeO2 NPs, treatment in AD induced by AlCl3 inhibited amyloid-β1–42, substantially enhanced the memory, the cognition coordination of movement in part AD pathogenesis may be alleviated through reducing amyloidogenic pathway and AChE and BuChE activities. The findings of this work provide important comprehension of the chemoprotective activities of iridoids combined with nanoparticles. This could be useful in the development of new therapeutic methods for the treatment of neurodegenerative diseases.
The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells
Authors: Ford Hunter R. , Bionaz Massimo
Published: April 2024

Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, the periparturient period, when dairy cows must rapidly adapt to the sudden metabolic demands of lactation, is a period when the production of damaging free radicals can overwhelm the natural antioxidant systems, potentially leading to tissue damage and reduced milk production. Central to the protection against free radical damage and antioxidant defense is the transcription factor NRF2, which activates an array of genes associated with antioxidant functions and cell survival. The objective of this study was to evaluate the effect that two natural NRF2 modulators, the NRF2 agonist sulforaphane (SFN) and the antagonist brusatol (BRU), have on the transcriptome of immortalized bovine mammary alveolar cells (MACT) using both the RT-qPCR of putative NRF2 target genes, as well as RNA sequencing approaches. The treatment of cells with SFN resulted in the activation of many putative NRF2 target genes and the upregulation of genes associated with pathways involved in cell survival, metabolism, and antioxidant function while suppressing the expression of genes related to cellular senescence and DNA repair. In contrast, the treatment of cells with BRU resulted in the upregulation of genes associated with inflammation, cellular stress, and apoptosis while suppressing the transcription of genes involved in various metabolic processes. The analysis also revealed several novel putative NRF2 target genes in bovine. In conclusion, these data indicate that the treatment of cells with SFN and BRU may be effective at modulating the NRF2 transcriptional network, but additional effects associated with cellular stress and metabolism may complicate the effectiveness of these compounds to improve antioxidant health in dairy cattle via nutrigenomic approaches.
Neutrophil Elastase Degrades Histone Deacetylases and Sirtuin 1 in Primary Human Monocyte Derived Macrophages
Authors: Zheng Shuo , Bulut Gamze B. , Kummarapurugu Apparao B. , Ma Jonathan , Voynow Judith A.
Published: April 2024

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity, and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDMs) in vitro. Human BMDMs were exposed to NE or control vehicle, and the abundance of HDACs and Sirtuins was determined by Western blotting of total cell lysates or nuclear extracts or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1, which shifted BMDMs to a pro-inflammatory phenotype.
Association between Platelet-Derived Growth Factor Receptor Alpha Gene Polymorphisms and Platelet-Rich Plasma’s Efficiency in Treating Lateral Elbow Tendinopathy—A Prospective Cohort Study
Authors: Jarosz Alicja , Balcerzyk-Matić Anna , Iwanicka Joanna , Iwanicki Tomasz , Nowak Tomasz , Szyluk Karol , Kalita Marcin , Górczyńska-Kosiorz Sylwia , Kania Wojciech , Niemiec Paweł
Published: April 2024

Individual differences in the response to platelet-rich plasma (PRP) therapy can be observed among patients. The genetic background may be the cause of this variability. The current study focused on the impact of genetic variants on the effectiveness of PRP. The aim of the present study was to analyze the impact of single nucleotide polymorphisms (SNP) of the platelet-derived growth factor receptor alpha (PDGFRA) gene on the effectiveness of treating lateral elbow tendinopathy (LET) with PRP. The treatment’s efficacy was analyzed over time (2, 4, 8, 12, 24, 52 and 104 weeks after the PRP injection) on 107 patients using patient-reported outcome measures (PROM) and achievement of a minimal clinically important difference (MCID). Four SNPs of the PDGFRA gene (rs7668190, rs6554164, rs869978 and rs1316926) were genotyped using the TaqMan assay method. Patients with the AA genotypes of the rs7668190 and the rs1316926 polymorphisms, as well as carriers of the T allele of rs6554164 showed greater effectiveness of PRP therapy than carriers of other genotypes. Moreover, the studied SNPs influenced the platelets’ parameters both in whole blood and in PRP. These results showed that PDGFRA gene polymorphisms affect the effectiveness of PRP treatment. Genotyping the rs6554164 and the rs1316926 SNPs may be considered for use in individualized patient selection for PRP therapy.
The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases
Authors: Lee Seojin , Kovacs Gabor G.
Published: April 2024

Iron accumulation in the brain is a common feature of many neurodegenerative diseases. Its involvement spans across the main proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. Accumulating evidence supports the contribution of iron in disease pathologies, but the delineation of its pathogenic role is yet challenged by the complex involvement of iron in multiple neurotoxicity mechanisms and evidence supporting a reciprocal influence between accumulation of iron and protein pathology. Here, we review the major proteinopathy-specific observations supporting four distinct hypotheses: (1) iron deposition is a consequence of protein pathology; (2) iron promotes protein pathology; (3) iron protects from or hinders protein pathology; and (4) deposition of iron and protein pathology contribute parallelly to pathogenesis. Iron is an essential element for physiological brain function, requiring a fine balance of its levels. Understanding of disease-related iron accumulation at a more intricate and systemic level is critical for advancements in iron chelation therapies.
Correction: Kudłacik-Kramarczyk et al. Exploring the Potential of Royal-Jelly-Incorporated Hydrogel Dressings as Innovative Wound Care Materials. Int. J. Mol. Sci. 2023, 24, 8738
Authors: Kudłacik-Kramarczyk Sonia , Krzan Marcel , Jamroży Mateusz , Przybyłowicz Alicja , Drabczyk Anna
Published: April 2024

The authors wish to make the following corrections to this paper [...]
Development of a Novel, Potent, and Selective Sialyltransferase Inhibitor for Suppressing Cancer Metastasis
Authors: Tsai Han-En , Chen Chia-Ling , Chang Tzu-Ting , Fu Chih-Wei , Chen Wei-Chia , Perez Ser John Lynon P. , Hsiao Pei-Wen , Tai Ming-Hong , Li Wen-Shan
Published: April 2024

Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs. Herein, we report the inhibitory effects of a recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 and B16F10 cell migration and invasion, and in in vivo studies, on tumor growth, metastasis, and angiogenesis. FCW393 showed effective and selective inhibition of the sialyltransferases ST6GAL1 (IC50 = 7.8 μM) and ST3GAL3 (IC50 = 9.45 μM) relative to ST3GAL1 (IC50 > 400 μM) and ST8SIA4 (IC50 > 100 μM). FCW393 reduced integrin sialylation in breast cancer and melanoma cells dose-dependently and downregulated proteins associated with the integrin-regulated FAK/paxillin and GEF/Rho/ROCK pathways, and with the VEGF-regulated Akt/NFκB/HIF-1α pathway. FCW393 inhibited cell migration (IC50 = 2.6 μM) and invasion in in vitro experiments, and in in vivo studies of tumor-bearing mice, FCW393 reduced tumor size, angiogenesis, and metastatic potential. Based on its demonstrated selectivity, cell permeability, relatively low cytotoxicity (IC50 = 55 μM), and high efficacy, FCW393 shows promising potential as a small molecule experimental tool compound and a lead for further development of a novel cancer therapeutic.
A Role in 15-Deacetylcalonectrin Acetylation in the Non-Enzymatic Cyclization of an Earlier Bicyclic Intermediate in Fusarium Trichothecene Biosynthesis
Authors: Koizumi Yoshiaki , Nakajima Yuichi , Tanaka Yuya , Matsui Kosuke , Sakabe Masato , Maeda Kazuyuki , Sato Masayuki , Koshino Hiroyuki , Sato Soichi , Kimura Makoto , Takahashi-Ando Naoko
Published: April 2024

The trichothecene biosynthesis in Fusarium begins with the cyclization of farnesyl pyrophosphate to trichodiene, followed by subsequent oxygenation to isotrichotriol. This initial bicyclic intermediate is further cyclized to isotrichodermol (ITDmol), a tricyclic precursor with a toxic trichothecene skeleton. Although the first cyclization and subsequent oxygenation are catalyzed by enzymes encoded by Tri5 and Tri4, the second cyclization occurs non-enzymatically. Following ITDmol formation, the enzymes encoded by Tri101, Tri11, Tri3, and Tri1 catalyze 3-O-acetylation, 15-hydroxylation, 15-O-acetylation, and A-ring oxygenation, respectively. In this study, we extensively analyzed the metabolites of the corresponding pathway-blocked mutants of Fusarium graminearum. The disruption of these Tri genes, except Tri3, led to the accumulation of tricyclic trichothecenes as the main products: ITDmol due to Tri101 disruption; a mixture of isotrichodermin (ITD), 7-hydroxyisotrichodermin (7-HIT), and 8-hydroxyisotrichodermin (8-HIT) due to Tri11 disruption; and a mixture of calonectrin and 3-deacetylcalonectrin due to Tri1 disruption. However, the ΔFgtri3 mutant accumulated substantial amounts of bicyclic metabolites, isotrichotriol and trichotriol, in addition to tricyclic 15-deacetylcalonectrin (15-deCAL). The ΔFgtri5ΔFgtri3 double gene disruptant transformed ITD into 7-HIT, 8-HIT, and 15-deCAL. The deletion of FgTri3 and overexpression of Tri6 and Tri10 trichothecene regulatory genes did not result in the accumulation of 15-deCAL in the transgenic strain. Thus, the absence of Tri3p and/or the presence of a small amount of 15-deCAL adversely affected the non-enzymatic second cyclization and C-15 hydroxylation steps.
Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia Experiencing Acute Psychosis
Authors: Miyano Takuya , Mikkaichi Tsuyoshi , Nakamura Kouichi , Yoshigae Yasushi , Abernathy Kelly , Ogura Yuji , Kiyosawa Naoki
Published: April 2024

Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched ‘Immune Response’ according to miRNA set enrichment analysis and were reported to negatively regulate IL-1β, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched ‘Cytokine-cytokine receptor interaction’ according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.
Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome
Authors: Chimienti Guglielmina , Russo Francesco , Bianco Antonella , Maqoud Fatima , De Virgilio Caterina , Galeano Grazia , Orlando Antonella , Riezzo Giuseppe , D’Attoma Benedetta , Ignazzi Antonia , Linsalata Michele , Prospero Laura , Franco Isabella , Bagnato Claudia Beatrice , Curci Ritanna , Coletta Sergio
Published: April 2024

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.
Meta-Quantitative Trait Loci Analysis and Candidate Gene Mining for Drought Tolerance-Associated Traits in Maize (Zea mays L.)
Authors: Li Ronglan , Wang Yueli , Li Dongdong , Guo Yuhang , Zhou Zhipeng , Zhang Mi , Zhang Yufeng , Würschum Tobias , Liu Wenxin
Published: April 2024

Drought is one of the major abiotic stresses with a severe negative impact on maize production globally. Understanding the genetic architecture of drought tolerance in maize is a crucial step towards the breeding of drought-tolerant varieties and a targeted exploitation of genetic resources. In this study, 511 quantitative trait loci (QTL) related to grain yield components, flowering time, and plant morphology under drought conditions, as well as drought tolerance index were collected from 27 published studies and then projected on the IBM2 2008 Neighbors reference map for meta-analysis. In total, 83 meta-QTL (MQTL) associated with drought tolerance in maize were identified, of which 20 were determined as core MQTL. The average confidence interval of MQTL was strongly reduced compared to that of the previously published QTL. Nearly half of the MQTL were confirmed by co-localized marker-trait associations from genome-wide association studies. Based on the alignment of rice proteins related to drought tolerance, 63 orthologous genes were identified near the maize MQTL. Furthermore, 583 candidate genes were identified within the 20 core MQTL regions and maize–rice homologous genes. Based on KEGG analysis of candidate genes, plant hormone signaling pathways were found to be significantly enriched. The signaling pathways can have direct or indirect effects on drought tolerance and also interact with other pathways. In conclusion, this study provides novel insights into the genetic and molecular mechanisms of drought tolerance in maize towards a more targeted improvement of this important trait in breeding.
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management
Authors: Loriamini Melika , Cserti-Gazdewich Christine , Branch Donald R.
Published: April 2024

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one’s own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath–Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.
Design, Construction and Programming of a Low-Cost Pulsed High-Voltage Direct Current Power Supply for the Electrophoretic Deposition of Silicon Carbide Mixed with Graphite and/or Alumina for Thermoelectric Applications
Authors: Reyes Valdez Juan Jesús , De la Cruz Terrazas Edna Carina , Rodríguez González Eugenio
Published: April 2024

This document describes a proprietary design, construction, programming and testing of a low-cost pulsed high-voltage direct current (HVDC) power supply with an output of 430 V and power of 25 W. The design obtained allows costs to be reduced compared to commercial ones, highlighting that the manufacturing of this HVDC is easy to replicate. To demonstrate the operation of the pulsed power supply prototype, coatings of silicon carbide (SiC) and SiC mixed with graphite (C) and/or alumina (Al2O3) were made using the electrophoretic deposition (EPD) method. After processing, samples underwent a heat treatment at 500 °C to evaluate their thermoelectric (TE) efficiency. The samples were analysed via X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, Seebeck coefficient, electrical conductivity and thermal conductivity. The Seebeck coefficient, electrical conductivity and thermal conductivity were measured in a temperature range of 100–500 °C in a nitrogen (N2) atmosphere. The electrical conductivity of the SiC 6C-4Al sample was 0.65 S/cm at 500 °C, while the maximum Seebeck coefficient was 2500 μV/K of the SiC 6C-4Al sample at 200 °C. The thermal conductivity of SiC 6C-4Al was in the range of 0.35–0.37 W/m·K, which was much lower than the SiC sample free of alumina and graphite in the same measured temperature range. In conclusion, the SiC 6C-4Al sample presented the highest figure of merit with a ZT ≈ 0.01.
Characteristics of Lightweight Concrete Fabricated with Different Types of Strengthened Lightweight Aggregates
Authors: Mahmmod Laith Mohammed Ridha , Dulaimi Anmar , Bernardo Luís Filipe Almeida , Andrade Jorge Miguel de Almeida
Published: April 2024

The vast majority of different waste building units have negative environmental impacts around the world. Crushed building units can be recycled and utilized in the concrete industry to solve these problems and maintain natural resources. This study investigated the feasibility of employing crushed autoclaved aerated concrete (CAAC) and crushed clay brick (CCB) as a lightweight aggregate (LWA) to fabricate environmentally friendly recycled lightweight concrete (LWC). In addition, a lightweight expanded clay aggregate (LECA) was also used as an LWA, namely to study how the high porosity of an LWA can adversely affect the properties of LWC. Through the experimental program, all types of LWAs were pre-treated and strengthened with two cementitious grouts, and then the performance of the produced LWC was assessed by determining the slump of fresh concrete, the dry density, the unconfined compressive strength, and the splitting tensile strength at ages of 3, 7, 28, and 56 days. The laboratory results revealed that both CCB and CAAC can be reused as full substitutions for normal-weight coarse aggregate to manufacture LWC with appropriate properties. The obtained data show that the properties of an LECA, CCB, and CAAC were improved, and the porous structure can be strengthened by pre-treatment and coating with grouts. In the same way, the mechanical performance of produced LWC is also enhanced.
The Three-Dimensional Printing of Composites: A Review of the Finite Element/Finite Volume Modelling of the Process
Authors: Zach Theodor Florian , Dudescu Mircea Cristian
Published: April 2024

Composite materials represent the evolution of material science and technology, maximizing the properties for high-end industry applications. The fields concerned include aerospace and defense, automotive, or naval industries. Additive manufacturing (AM) technologies are increasingly growing in market shares due to the elimination of shape barriers, a plethora of available materials, and the reduced costs. The AM technologies of composite materials combine the two growing trends in manufacturing, combining the advantages of both, with a specific enhancement being the elimination of the need for mold manufacturing for composites, or even post-curing treatments. The challenge of AM composites is to compete with their conventional counterparts. The aim of the current paper is to present the additive manufacturing process across different spectrums of finite element analyses (FEA). The first outcomes are building definition (support definition) and the optimization of deposition trajectories. In addition, the multi-physics of melting/solidification using computational fluid dynamics (CFD) are performed to predict the fiber orientation and extrusion profiles. The process modelling continues with the displacement/temperature distribution, which influences porosity, warping, and residual stresses that influence characteristics of the component. This leads to the tuning of the technological parameters, thus improving the manufacturing process.
Surgical Outcomes and Complications of Custom-Made Prostheses in Upper Limb Oncological Reconstruction: A Systematic Review
Authors: Fulchignoni Camillo , Pietramala Silvia , Lopez Ivo , Mazzella Giovan Giuseppe , Comisi Chiara , Perisano Carlo , Rocchi Lorenzo , Greco Tommaso
Published: April 2024

Bone tumors of the upper limb are a common cause of bone pain and pathological fractures in both old and young populations. Surgical reconstruction and limb salvage have become valid options for these patients despite this kind of surgery being challenging due to the need for wide bone resection and the involvement of surrounding soft tissues. Computer-assisted technology helps the surgeon in pre-operative planning and in designing customized implants. The aim of this study was to investigate the surgical outcomes and complications of custom-made prostheses in oncologic reconstruction of the upper limb and if they are reliable options for patients suffering from aggressive tumors. An electronic search on PubMed, Google Scholar, and Web of Knowledge was conducted to identify all available articles on the use of custom-made prostheses in oncological resections of the upper limb. Twenty-one studies were included in the review, comprising a total of 145 patients with a mean age of 33.68 years. The bone involved was the humerus in 93 patients, and the radius was involved in 36 patients. There were only six cases involving proximal ulna, three cases involving the scapula, and seven cases involving the elbow as well as soft tissues around it. The most frequent primary tumor was the giant cell tumor, with 36 cases, followed by osteosarcoma with 25 cases, Ewing Sarcoma with 17 cases, and Chondrosarcoma with 7 total cases. Forty patients were affected by bone metastases (such as renal cell cancer, breast cancer, melanoma, and rectal cancer) or hematologic diseases involving bone (lymphoma, myeloma, or non-Hodgkin disease). Custom-made prostheses are a viable option for patients who suffer from malignant tumors in their upper limbs. They are a reliable aid for surgeons in cases of extensive resections.