The 2023 MDPI Annual Report has
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18 pages, 7171 KiB  
Article
Developing a High-Umami, Low-Salt Soy Sauce through Accelerated Moromi Fermentation with Corynebacterium and Lactiplantibacillus Strains
by Li-Hao Wang, Wen-Hui Qu, Ya-Nan Xu, Song-Gang Xia, Qian-Qian Xue, Xiao-Ming Jiang, Hong-Ying Liu, Chang-Hu Xue and Yun-Qi Wen
Foods 2024, 13(9), 1386; https://doi.org/10.3390/foods13091386 (registering DOI) - 30 Apr 2024
Abstract
The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji [...] Read more.
The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning. Full article
(This article belongs to the Section Food Microbiology)
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16 pages, 332 KiB  
Article
The Living and the Dead in Slavic Folk Culture: Modes of Interaction between Two Worlds
by Svetlana M. Tolstaya
Religions 2024, 15(5), 566; https://doi.org/10.3390/rel15050566 (registering DOI) - 30 Apr 2024
Abstract
Slavic folk culture is a fusion of Christian and of pre-Christian, pagan beliefs based on magic. This article is devoted specifically to ancient pre-Christian ideas about death and posthumous existence and the associated magical rituals and prohibitions, which persist to our time. It [...] Read more.
Slavic folk culture is a fusion of Christian and of pre-Christian, pagan beliefs based on magic. This article is devoted specifically to ancient pre-Christian ideas about death and posthumous existence and the associated magical rituals and prohibitions, which persist to our time. It considers the following interactions between the living and the dead: 1. the measures taken and prohibitions observed by the living to ensure their well-being in the other world; 2. the measures taken by the living to ensure the well-being of their dead relatives in the other world (including funeral rites; memorial rites; cemetery visits; providing the dead with food, clothes, and items necessary for postmortem life; and sending messages to the other world); 3. communication between the living and the dead on certain days (including taking opportunities to meet, see, and hear them; treat them; prepare a bed for them; and wash them); 4. fear of the dead and their return and the desire to placate them to prevent them from causing natural disasters (hail, droughts, floods, etc.), crop failures, cattle deaths, diseases, and death; 5. magical ways for protecting oneself from the “walking dead”; 6. transforming the dead into mythological characters—for example, house-, water-, or forest-spirits and mermaids. The material presented in the article is drawn from published and archival sources collected by folklorists and ethnographers of the XIX and XX centuries in different regions of the Slavic world, as well as from field recordings made by the author and his colleagues in Polesie, the borderland of Belarus and Ukraine, in the 1960–1980s, in the Russian North and in the Carpathian region in the 1990s. It shows that the relationship between the living and the dead in folk beliefs does not fit comfortably within the widespread notion of an “ancestor cult”. It argues that the dead are both venerated and feared and that the living feel a dependence on their ancestors and a desire to strictly observe the boundary between the two worlds. Full article
(This article belongs to the Special Issue Communication with the Dead)
18 pages, 4897 KiB  
Article
Enhancing Transparency in Non-Cubic Calcium Phosphate Ceramics: Effect of Starting Powder, LiF Doping, and Spark Plasma Sintering Parameters
by Kacper Albin Prokop, Sandrine Cottrino, Vincent Garnier, Gilbert Fantozzi, Yannick Guyot, Georges Boulon and Małgorzata Guzik
Ceramics 2024, 7(2), 607-624; https://doi.org/10.3390/ceramics7020040 (registering DOI) - 30 Apr 2024
Abstract
Our objective is to achieve a new good-quality and mechanically durable high-transparency material that, when activated by rare earth ions, can be used as laser sources, scintillators, or phosphors. The best functional transparent ceramics are formed from high-symmetry systems, mainly cubic. Considering hexagonal [...] Read more.
Our objective is to achieve a new good-quality and mechanically durable high-transparency material that, when activated by rare earth ions, can be used as laser sources, scintillators, or phosphors. The best functional transparent ceramics are formed from high-symmetry systems, mainly cubic. Considering hexagonal hydroxyapatite, which shows anisotropy, the particle size of the initial powder is extremely important and should be of the order of several tens of nanometers. In this work, transparent micro-crystalline ceramics of non-cubic Ca10(PO4)6(OH)2 calcium phosphate were fabricated via Spark Plasma Sintering (SPS) from two types of nanopowders i.e., commercially available (COM. HA) and laboratory-made (LAB. HA) via the hydrothermal (HT) protocol. Our study centered on examining how the quality of sintered bodies is affected by the following parameters: the addition of LiF sintering agent, the temperature during the SPS process, and the quality of the starting nanopowders. The phase purity, microstructure, and optical transmittance of the ceramics were investigated to determine suitable sintering conditions. The best optical ceramics were obtained from LAB. HA nanopowder with the addition of 0.25 wt.% of LiF sintered at 1000 °C and 1050 °C. Full article
(This article belongs to the Special Issue Transparent Ceramics—a Theme Issue in Honor of Dr. Adrian Goldstein)
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14 pages, 1218 KiB  
Article
A Pilot Study of the Clinical Effectiveness of a Single Intra-Articular Injection of Stanozolol in Canines with Knee Degenerative Joint Disease and Its Correlation with Serum Interleukin-1β Levels
by L. Miguel Carreira, João Cota, Joao Alves, Filipa Inácio, Graça Alexandre-Pires and Pedro Azevedo
Animals 2024, 14(9), 1351; https://doi.org/10.3390/ani14091351 (registering DOI) - 30 Apr 2024
Abstract
Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1β levels. Thirty dogs (n = [...] Read more.
Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1β levels. Thirty dogs (n = 30) were divided into a control group (CG, n = 10) and a study group (SG, n = 20) with DJD. Pain levels were assessed using the Brown query, and radiographs were taken at T0 and T3. IL-1β levels were quantified via ELISA. Apart from 2 patients, all showed reduced pain intensity, with 15 patients showing improvement at T1 and 3 patients at T2. A positive correlation (r = 0.84; p < 0.01) was found between pain level and IL-1β in 15 patients. No systemic effects were observed. Most patients (18/20) experienced reduced pain. This pilot study suggests stanozolol’s potential in managing DJD in dogs. Further research is warranted to validate these findings and understand stanozolol’s mechanism in DJD treatment. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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14 pages, 3784 KiB  
Article
Effect of Different Hydrocolloids on the Qualitative Characteristics of Fermented Gluten-Free Quinoa Dough and Bread
by Tiziana Di Renzo, Maria Carmela Trivisonno, Stefania Nazzaro, Anna Reale and Maria Cristina Messia
Foods 2024, 13(9), 1382; https://doi.org/10.3390/foods13091382 (registering DOI) - 30 Apr 2024
Abstract
The aim of this research was to optimize the production process of fermented gluten-free quinoa bread. To this end, the effect of different hydrocolloids on the technological, fermentative, and nutritional properties of quinoa-based gluten-free doughs and breads was evaluated. For this purpose, 3% [...] Read more.
The aim of this research was to optimize the production process of fermented gluten-free quinoa bread. To this end, the effect of different hydrocolloids on the technological, fermentative, and nutritional properties of quinoa-based gluten-free doughs and breads was evaluated. For this purpose, 3% of four different hydrocolloids (sodium alginate, k-carrageenan, xanthan gum, and hydroxypropyl methylcellulose (HPMC)) were used in gluten-free doughs composed of 50% quinoa flour, 20% rice flour, and 30% potato starch. The rheological and fermentative properties of the doughs were evaluated, as well as the chemical composition, specific volume, crust and crumb color, and alveolar structure profile of gluten-free breads. The results highlighted the differences in dough rheology during mixing and fermentation of the doughs. In particular, HPMC showed a good gas retention (93%) during the fermentation of quinoa dough by registering the highest maximum dough development height (Hm). The gluten-free quinoa breads obtained were characterized by significantly different quality parameters (p < 0.05). The use of 3% HPMC resulted in breads with the lowest baking loss, the highest volume, and the most open crumb structure. Full article
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20 pages, 2552 KiB  
Article
Identifying the Effect of Cognitive Motivation with the Method Based on Temporal Association Rule Mining Concept
by Tustanah Phukhachee, Suthathip Maneewongvatana, Chayapol Chaiyanan, Keiji Iramina and Boonserm Kaewkamnerdpong
Sensors 2024, 24(9), 2857; https://doi.org/10.3390/s24092857 (registering DOI) - 30 Apr 2024
Abstract
Being motivated has positive influences on task performance. However, motivation could result from various motives that affect different parts of the brain. Analyzing the motivation effect from all affected areas requires a high number of EEG electrodes, resulting in high cost, inflexibility, and [...] Read more.
Being motivated has positive influences on task performance. However, motivation could result from various motives that affect different parts of the brain. Analyzing the motivation effect from all affected areas requires a high number of EEG electrodes, resulting in high cost, inflexibility, and burden to users. In various real-world applications, only the motivation effect is required for performance evaluation regardless of the motive. Analyzing the relationships between the motivation-affected brain areas associated with the task’s performance could limit the required electrodes. This study introduced a method to identify the cognitive motivation effect with a reduced number of EEG electrodes. The temporal association rule mining (TARM) concept was used to analyze the relationships between attention and memorization brain areas under the effect of motivation from the cognitive motivation task. For accuracy improvement, the artificial bee colony (ABC) algorithm was applied with the central limit theorem (CLT) concept to optimize the TARM parameters. From the results, our method can identify the motivation effect with only FCz and P3 electrodes, with 74.5% classification accuracy on average with individual tests. Full article
(This article belongs to the Special Issue EEG Signal Processing Techniques and Applications—2nd Edition)
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13 pages, 1765 KiB  
Article
Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice
by Ivan V. Chernikov, Irina K. Bachkova, Aleksandra V. Sen’kova, Mariya I. Meschaninova, Innokenty A. Savin, Valentin V. Vlassov, Marina A. Zenkova and Elena L. Chernolovskaya
Cells 2024, 13(9), 767; https://doi.org/10.3390/cells13090767 (registering DOI) - 30 Apr 2024
Abstract
Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding their applications to various organs, including the lungs. Cholesterol-conjugated [...] Read more.
Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding their applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs. Full article
(This article belongs to the Special Issue RNA in Focus)
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35 pages, 8530 KiB  
Article
Structure–Function Analysis of the Essential Mycobacterium tuberculosis P450 Drug Target, CYP121A1
by Tiara Padayachee, David C. Lamb, David R. Nelson and Khajamohiddin Syed
Int. J. Mol. Sci. 2024, 25(9), 4886; https://doi.org/10.3390/ijms25094886 (registering DOI) - 30 Apr 2024
Abstract
Cytochrome P450 CYP121A1 is a well-known drug target against Mycobacterium tuberculosis, the human pathogen that causes the deadly disease tuberculosis (TB). CYP121A1 is a unique P450 enzyme because it uses classical and non-classical P450 catalytic processes and has distinct structural features among [...] Read more.
Cytochrome P450 CYP121A1 is a well-known drug target against Mycobacterium tuberculosis, the human pathogen that causes the deadly disease tuberculosis (TB). CYP121A1 is a unique P450 enzyme because it uses classical and non-classical P450 catalytic processes and has distinct structural features among P450s. However, a detailed investigation of CYP121A1 protein structures in terms of active site cavity dynamics and key amino acids interacting with bound ligands has yet to be undertaken. To address this research knowledge gap, 53 CYP121A1 crystal structures were investigated in this study. Critical amino acids required for CYP121A1’s overall activity were identified and highlighted this enzyme’s rigid architecture and substrate selectivity. The CYP121A1-fluconazole crystal structure revealed a novel azole drug–P450 binding mode in which azole heme coordination was facilitated by a water molecule. Fragment-based inhibitor approaches revealed that CYP121A1 can be inhibited by molecules that block the substrate channel or by directly interacting with the P450 heme. This study serves as a reference for the precise understanding of CYP121A1 interactions with different ligands and the structure–function analysis of P450 enzymes in general. Our findings provide critical information for the synthesis of more specific CYP121A1 inhibitors and their development as novel anti-TB drugs. Full article
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18 pages, 1847 KiB  
Review
Supposed Virulence Factors of Flavobacterium psychrophilum: A Review
by Věra Vaibarová and Alois Čížek
Fishes 2024, 9(5), 163; https://doi.org/10.3390/fishes9050163 (registering DOI) - 30 Apr 2024
Abstract
Flavobacterium psychrophilum is currently one of the most important pathogens in aquaculture worldwide, causing high losses to farmed salmonids particularly during early growth stages with significant economic impact. Despite previous attempts, no effective vaccine has been developed, and protection against introduction into farms [...] Read more.
Flavobacterium psychrophilum is currently one of the most important pathogens in aquaculture worldwide, causing high losses to farmed salmonids particularly during early growth stages with significant economic impact. Despite previous attempts, no effective vaccine has been developed, and protection against introduction into farms is difficult due to the ubiquitous occurrence of the pathogen. A better understanding of the mechanism of disease development is essential for targeted therapeutic and preventive measures in farms. Unfortunately, the pathogenesis of diseases caused by F. psychrophilum has not been elucidated yet. Previously, several putative virulence factors have been identified. Some appear to be essential for disease development, while others are probably dispensable. The importance of some factors has not yet been explored. This review focuses on the supposed virulence factors of F. psychrophilum and the current knowledge about their importance in the pathogenesis of the disease. Full article
(This article belongs to the Special Issue Fish Pathogens: Infection and Biological Control)
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14 pages, 2608 KiB  
Article
Long-Range Effects in Topologically Defective Arm-Chair Graphene Nanoribbons
by Enrique Louis, Guillermo Chiappe, José A. Vergés and Emilio San-Fabián
Nanomaterials 2024, 14(9), 778; https://doi.org/10.3390/nano14090778 (registering DOI) - 30 Apr 2024
Abstract
The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state-of-the-art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one [...] Read more.
The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state-of-the-art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states that interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological states, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented by adding an exponential cutoff to the interaction term of the PPP model. In this way, an adjusted cutoff distance λ=2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond the Hubbard model but not completely unscreened as is the case for the PPP model. Full article
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21 pages, 976 KiB  
Article
CCTFv2: Modeling Cyber Competitions
by Basheer Qolomany, Tristan J. Calay, Liaquat Hossain, Aos Mulahuwaish and Jacques Bou Abdo
Entropy 2024, 26(5), 384; https://doi.org/10.3390/e26050384 (registering DOI) - 30 Apr 2024
Abstract
Cyber competitions are usually team activities, where team performance not only depends on the members’ abilities but also on team collaboration. This seems intuitive, especially given that team formation is a well-studied discipline in competitive sports and project management, but unfortunately, team performance [...] Read more.
Cyber competitions are usually team activities, where team performance not only depends on the members’ abilities but also on team collaboration. This seems intuitive, especially given that team formation is a well-studied discipline in competitive sports and project management, but unfortunately, team performance and team formation strategies are rarely studied in the context of cybersecurity and cyber competitions. Since cyber competitions are becoming more prevalent and organized, this gap becomes an opportunity to formalize the study of team performance in the context of cyber competitions. This work follows a cross-validating two-approach methodology. The first is the computational modeling of cyber competitions using Agent-Based Modeling. Team members are modeled, in NetLogo, as collaborating agents competing over a network in a red team/blue team match. Members’ abilities, team interaction and network properties are parametrized (inputs), and the match score is reported as output. The second approach is grounded in the literature of team performance (not in the context of cyber competitions), where a theoretical framework is built in accordance with the literature. The results of the first approach are used to build a causal inference model using Structural Equation Modeling. Upon comparing the causal inference model to the theoretical model, they showed high resemblance, and this cross-validated both approaches. Two main findings are deduced: first, the body of literature studying teams remains valid and applicable in the context of cyber competitions. Second, coaches and researchers can test new team strategies computationally and achieve precise performance predictions. The targeted gap used methodology and findings which are novel to the study of cyber competitions. Full article
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19 pages, 8452 KiB  
Review
Waves of Precision: A Practical Guide for Reviewing New Tools to Evaluate Mechanical In-Exsufflation Efficacy in Neuromuscular Disorders
by Michelle Chatwin, Jesus Sancho, Manel Lujan, Tiina Andersen and Joao-Carlos Winck
J. Clin. Med. 2024, 13(9), 2643; https://doi.org/10.3390/jcm13092643 (registering DOI) - 30 Apr 2024
Abstract
Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate [...] Read more.
Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate cough effectiveness with and without MI-E. This review highlights the limitations of this and discussed other tools to evaluate MI-E efficacy in this rapidly developing field. Such tools include the interpretation of parameters (like pressure, flow and volumes) that derive from the MI-E device and external methods to evaluate upper airway closure. In this review we pinpoint the differences between different devices in the market and discuss new tools to better titrate MI-E and detect pathological responses of the upper airway. We discuss the importance of point of care ultrasound (POCUS), transnasal fiberoptic laryngoscopy and wave form analysis in this setting. To improve clinical practice newer generation MI-E devices should allow real-time evaluation of waveforms and standardize some of the derived parameters. Full article
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21 pages, 10248 KiB  
Article
Biological Effects of PMMA and Composite Resins on Human Gingival Fibroblasts: An In Vitro Comparative Study
by Ylenia Della Rocca, Enrico Matteo Traini, Oriana Trubiani, Tonino Traini, Antonella Mazzone, Guya Diletta Marconi, Jacopo Pizzicannella and Francesca Diomede
Int. J. Mol. Sci. 2024, 25(9), 4880; https://doi.org/10.3390/ijms25094880 (registering DOI) - 30 Apr 2024
Abstract
The use of temporary resin for provisional restorations is a fundamental step to maintain the position of prepared teeth, to protect the pulpal vitality and the periodontal health as well as the occlusion. The present study aimed at evaluating the biological effects of [...] Read more.
The use of temporary resin for provisional restorations is a fundamental step to maintain the position of prepared teeth, to protect the pulpal vitality and the periodontal health as well as the occlusion. The present study aimed at evaluating the biological effects of two resins used in dentistry for temporary restorations, Coldpac (Yates Motloid) and ProTemp 4™ (3M ESPE ™), and their eluates, in an in vitro model of human gingival fibroblasts (hGFs). The activation of the inflammatory pathway NFκB p65/NLRP3/IL-1β induced by the self-curing resin disks was evaluated by real-time PCR, Western blotting and immunofluorescence analysis. The hGFs adhesion on resin disks was investigated by means of inverted light microscopy and scanning electron microscopy (SEM). Our results suggest that hGF cells cultured in adhesion and with eluate derived from ProTemp 4™ (3M ESPE ™) resin evidenced a downregulation in the expression of the inflammatory mediators such as NFκB p65, NLRP3 and IL-1β compared to the cells cultured with Coldpac (Yates Motloid) after 24 h and 1 week of culture. Furthermore, the cells cultured with ProTemp 4™ (3M ESPE ™) after 24 h and 1 week of culture reported a higher cell viability compared to the cells cultured with Coldpac (Yates Motloid), established by MTS cell analysis. Similar results were obtained when hGFs were placed in culture with the eluate derived from ProTemp 4™ (3M ESPE ™) resin which showed a higher cell viability compared to the cells cultured with eluate derived from Coldpac (Yates Motloid). These results highlighted the lower pro-inflammatory action and improved cell biocompatibility of ProTemp 4™ (3M ESPE ™), suggesting a better performance in terms of cells–material interaction. Full article
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14 pages, 3472 KiB  
Article
Overexpression of Fatty Acid Synthase Upregulates Glutamine–Fructose-6-Phosphate Transaminase 1 and O-Linked N-Acetylglucosamine Transferase to Increase O-GlcNAc Protein Glycosylation and Promote Colorectal Cancer Growth
by James Drury, Mariah E. Geisen, Josiane Weber Tessmann, Piotr G. Rychahou, Courtney O. Kelson, Daheng He, Chi Wang, B. Mark Evers and Yekaterina Y. Zaytseva
Int. J. Mol. Sci. 2024, 25(9), 4883; https://doi.org/10.3390/ijms25094883 (registering DOI) - 30 Apr 2024
Abstract
Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently [...] Read more.
Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently being tested in multiple clinical trials. However, the mechanisms behind the pro-oncogenic action of FASN are still not completely understood. Here, for the first time, we show that overexpression of FASN increases the expression of glutamine–fructose-6-phosphate transaminase 1 (GFPT1) and O-linked N-acetylglucosamine transferase (OGT), enzymes involved in hexosamine metabolism, and the level of O-GlcNAcylation in vitro and in vivo. Consistently, expression of FASN significantly correlates with expression of GFPT1 and OGT in human CRC tissues. shRNA-mediated downregulation of GFPT1 and OGT inhibits cellular proliferation and the level of protein O-GlcNAcylation in vitro, and knockdown of GFPT1 leads to a significant decrease in tumor growth and metastasis in vivo. Pharmacological inhibition of GFPT1 and OGT leads to significant inhibition of cellular proliferation and colony formation in CRC cells. In summary, our results show that overexpression of FASN increases the expression of GFPT1 and OGT as well as the level of protein O-GlcNAcylation to promote progression of CRC; targeting the hexosamine biosynthesis pathway could be a therapeutic approach for this disease. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Inhibition of Colorectal Cancer)
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14 pages, 1182 KiB  
Review
The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review
by Kyle Headen, Vaidile Jakaite, Vita Andreja Mesaric, Cristiano Scotta, Giovanna Lombardi, Kypros H. Nicolaides and Panicos Shangaris
Int. J. Mol. Sci. 2024, 25(9), 4884; https://doi.org/10.3390/ijms25094884 (registering DOI) - 30 Apr 2024
Abstract
Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. [...] Read more.
Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy. Full article
(This article belongs to the Special Issue Insights in Reproductive Immunology and Placental Pathology)
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12 pages, 26201 KiB  
Case Report
Surgical Treatment of Lithiasis of the Main Pancreatic Duct: A Challenging Case and a Literature Review
by Dan Brebu, Cătălin Prodan-Bărbulescu, Vlad Braicu, Paul Pașca, George Borcean, Sabrina Florea, Clarisa Bîrlog, Amadeus Dobrescu, Mărioara Cornianu, Fulger Lazăr, Bogdan Totolici, Ciprian Duță and Flaviu Ionuț Faur
Diseases 2024, 12(5), 86; https://doi.org/10.3390/diseases12050086 (registering DOI) - 30 Apr 2024
Abstract
Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic [...] Read more.
Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic parenchyma, and pancreatic fluid stasis at the ductal level are factors that contribute to the phenomenon of calcium precipitation. This article describes the case of a patient with a diagnosis of pancreaticolithiasis (Wirsung duct lithiasis), a phenomenon superimposed on chronic pancreatitis of ethanolic cause (Rosemont classification). It was decided to perform surgery via the classical approach with the perfection of corporeo-caudal pancreatectomy and preservation of the splenic vessels (Kimura procedure) with pancreatico-jejunal anastomosis on the Roux-en-Y loop. The aim of this study is to identify the best method of treatment for pancreaticolithiasis. To enhance the case and provide a basis for standardization, a literature review was carried out, which included a total of six articles. The results of this study highlight that, currently, the management of symptomatic pancreaticolithiasis encompasses medical therapy (enzyme replacement therapy), interventional therapy (ESWL (extracorporeal shock wave lithotripsy) ± ERCP (endoscopic retrograde cholangiopancreatography), ERCP + sphincterotomy + stent insertion, and POP (oral pancreatoscopy)), and surgical treatment. In conclusion, based on the analysis conducted in this study, the size of the calculi present determines which is the suitable therapeutic care. Unlike stones over 0.5 cm, when surgery is explicitly advised for therapeutic purposes in the absence of endoscopic techniques, stones under 0.5 cm should be treated using endoscopic procedures. Full article
(This article belongs to the Section Gastroenterology)
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9 pages, 1237 KiB  
Article
Identification of an Objective Cut-Off Point to Define the Clinical Stage T4a in Colon Cancer
by Carolina Bautista-Saiz, Luisa F. Rivera-Moncada, Leonardo S. Lino-Silva, Guillermo A. Pérez-Correa and Pedro Frías-Fernández
Gastroenterol. Insights 2024, 15(2), 366-374; https://doi.org/10.3390/gastroent15020025 (registering DOI) - 30 Apr 2024
Abstract
Introduction: The current state of pathology practice and the variability in diagnosing pT4a colon cancer have been underexplored in existing studies. Our objective was to establish a specific cutoff point to distinguish between the pathological stages of pT3 and pT4a in colon cancer. [...] Read more.
Introduction: The current state of pathology practice and the variability in diagnosing pT4a colon cancer have been underexplored in existing studies. Our objective was to establish a specific cutoff point to distinguish between the pathological stages of pT3 and pT4a in colon cancer. Methods: We conducted a cross-sectional study involving pT3 and pT4 (pN0-2, cM0) colon cancers, measuring the distance to the serosa. Patients were categorized and analyzed based on this distance and the peritoneal reaction, with the aim being to ascertain their prognostic implications. Results: A total of 384 patients were analyzed. Patients with a distance between the invading front of cancer and the serosa ≥ 1 mm without a peritoneal reaction exhibited a median survival of 118 months, contrasting the amount of 70 months for those with <1 mm plus peritoneal reaction. Only lengths <1 mm with peritoneal reaction showed a significant correlation with mortality (p < 0.001). Conclusion: Our study revealed that patients in whom neoplastic cells were less than 1 mm from the serosal surface, accompanied by a peritoneal reaction (hemorrhage, inflammation, neovascularization, fibrin), had significantly lower survival rates compared to those with more than 1 mm distance and without peritoneal response (70 vs. 118 months, p < 0.001). Hence, such cases should be considered within the pT4a stage. Full article
(This article belongs to the Collection Advances in Gastrointestinal Cancer)
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13 pages, 535 KiB  
Article
Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock Despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia
by Weiqin Lin, Alfred Chung Lum Yip, Robin Cherian, Siew Pang Chan, Lauren Kay Mance Evangelista, Novi Yanti Sari, Hwei Sung Ling, Yoke Ching Lim, Raymond Ching Chiew Wong, Benjamin Wei Liang Tung, Li-Ling Tan, Adrian F. Low, Anand Adinath Ambhore and Shir Lynn Lim
Life 2024, 14(5), 577; https://doi.org/10.3390/life14050577 (registering DOI) - 30 Apr 2024
Abstract
Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify [...] Read more.
Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017–2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28–7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18–4.96), lower arterial pH (aOR 0.02, CI 0.00–0.31), higher lactate (aOR 2.42, CI 1.00–1.19), and lower hemoglobin (aOR 0.83, CI 0.71–0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS. Full article
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14 pages, 1260 KiB  
Review
Seeing and Sensing the Hepatorenal Syndrome (HRS): The Growing Role of Ultrasound-Based Techniques as Non-Invasive Tools for the Diagnosis of HRS
by Cornelia Tăluță, Horia Ștefănescu and Dana Crișan
Diagnostics 2024, 14(9), 938; https://doi.org/10.3390/diagnostics14090938 (registering DOI) - 30 Apr 2024
Abstract
More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last [...] Read more.
More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome. Full article
(This article belongs to the Special Issue Diagnostic Imaging of Liver Diseases)
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13 pages, 2209 KiB  
Article
Prognostic Nutritional Index and Instant Nutritional Assessement Are Associated with Clinical Outcomes in a Geriatric Cohort of Acutely Inpatients
by Cristiano Capurso, Aurelio Lo Buglio, Francesco Bellanti and Gianluigi Vendemiale
Nutrients 2024, 16(9), 1359; https://doi.org/10.3390/nu16091359 (registering DOI) - 30 Apr 2024
Abstract
Background: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization. Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. [...] Read more.
Background: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization. Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization. Results: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization. Conclusions: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments. Full article
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19 pages, 2925 KiB  
Review
The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia
by Martijn W. C. Verbeek and Vincent H. J. van der Velden
Int. J. Mol. Sci. 2024, 25(9), 4881; https://doi.org/10.3390/ijms25094881 (registering DOI) - 30 Apr 2024
Abstract
Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based [...] Read more.
Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium’s eight-color protocol, can achieve sensitivities down to 10−5 (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL. Full article
(This article belongs to the Special Issue Trends and Prospects of Flow Cytometry in Cell and Molecular Biology)
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19 pages, 12359 KiB  
Review
Recent Advances in Self-Assembled Molecular Application in Solar Cells
by Linkun Zhong, Chuangping Liu, Shi Lai, Bing’e Li, Baihong Zheng and Xiaoli Zhang
Nanomaterials 2024, 14(9), 779; https://doi.org/10.3390/nano14090779 (registering DOI) - 30 Apr 2024
Abstract
Perovskite solar cells (PSCs) have attracted much attention due to their low cost, high efficiency, and solution processability. With the development of various materials in perovskite solar cells, self-assembled monolayers (SAMs) have rapidly become an important factor in improving power conversion efficiency (PCE) [...] Read more.
Perovskite solar cells (PSCs) have attracted much attention due to their low cost, high efficiency, and solution processability. With the development of various materials in perovskite solar cells, self-assembled monolayers (SAMs) have rapidly become an important factor in improving power conversion efficiency (PCE) due to their unique physical and chemical properties and better energy level matching. In this topical review, we introduced important categories of self-assembled molecules, energy level modulation strategies, and various characteristics of self-assembled molecules. In addition, we focused on reviewing the application of self-assembled molecules in solar cells, and explained the changes that self-assembled molecules bring to PSCs by introducing the mechanism and effect of self-assembled molecules. Finally, we also elaborated on the challenges currently faced by self-assembled molecules and provided prospects for their applications in other optoelectronic devices. Full article
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12 pages, 631 KiB  
Article
Consumer Behaviour Regarding Certified Food
by Ilenia Bravo, Ilenia Colamatteo, Simona Balzano, Lucio Cappelli and Enrica Iannucci
Sustainability 2024, 16(9), 3757; https://doi.org/10.3390/su16093757 (registering DOI) - 30 Apr 2024
Abstract
The consumer decision-making process for buying food products is based on various factors. One of these is the perceived value that the consumer acquires upon seeing a certification label, such as “Protected Designation of Origin” (PDO) and “Protected Geographical Indication” (PGI), which is [...] Read more.
The consumer decision-making process for buying food products is based on various factors. One of these is the perceived value that the consumer acquires upon seeing a certification label, such as “Protected Designation of Origin” (PDO) and “Protected Geographical Indication” (PGI), which is an indicator of product quality and the degree of sustainability of the supply chain. The aim of the study is to identify the main factors influencing the behaviour and purchasing intentions of Italian consumers through the divulgation of a survey and the application of a statistical approach. The results were elaborated upon using a conceptual model, estimated following the partial least squares approach to structural equation modelling. As a result, the perception of quality influences purchasing decisions and food patterns, as labels play an increasing role in contemporary society, thus making quality standards relevant for the buying outcome. This research contributes to supporting studies on the importance of certifications of origin, as well as highlighting that food safety is a major determinant in the purchasing of certified food products. Full article
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