The 2023 MDPI Annual Report has
been released!
 
10 pages, 13101 KiB  
Case Report
Multiple Primary Melanoma Associated with CDKN2A Mutation—Case Report and Review of the Literature
by Luana-Andreea Nurla, Mariana Aşchie, Georgeta Camelia Cozaru and Mădălina Boșoteanu
Medicina 2024, 60(5), 763; https://doi.org/10.3390/medicina60050763 (registering DOI) - 05 May 2024
Abstract
The CDKN2A gene remains understudied in melanoma compared to BRAF alterations. Inactivation of this tumor suppressor gene through homozygous deletions in the 9p21 chromosomal region leads to cellular proliferation and disrupts pro-apoptotic pathways. Genetic changes in CDKN2A are linked to multiple primary melanomas [...] Read more.
The CDKN2A gene remains understudied in melanoma compared to BRAF alterations. Inactivation of this tumor suppressor gene through homozygous deletions in the 9p21 chromosomal region leads to cellular proliferation and disrupts pro-apoptotic pathways. Genetic changes in CDKN2A are linked to multiple primary melanomas (MPM), with patients diagnosed with melanoma facing an elevated risk of developing additional primaries. We present the rare case of a 72-year-old Caucasian woman with nine metastasizing melanomas across diverse anatomical sites, posing a diagnostic challenge. Initial diagnosis in 2022 revealed ulcerated superficial spreading melanomas, progressing to intradermal and papillary dermal populations with neurotropism and angiotropism by early 2023. Lymph node metastases were identified, classifying the condition as pT3b N3b. Subsequent assessments in April 2023 revealed clinically suspicious melanocytic lesions diagnosed as intradermal and traumatized junctional nevi. In late 2023, cutaneous pigmented lesions and subcutaneous metastases were confirmed as nodular nevoid low-CSD multiple melanomas. Fluorescence in situ hybridization testing revealed homozygous CDKN2A deletion, necessitating close multidisciplinary collaboration for an optimized care plan for effective monitoring and intervention in this intricate clinical scenario. In summary, this case report highlights the diagnostic challenges of MPM in a single patient. Stressing the importance of immuno-histochemistry and CDKN2A genetic testing, our findings underscore the crucial role of these tools in accurately distinguishing malignant melanocytic proliferations from nevi and characterizing MPM cases. Full article
(This article belongs to the Section Dermatology)
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19 pages, 5597 KiB  
Article
Regional Variation of the CD4 and CD8 T Cell Epitopes Conserved in Circulating Dengue Viruses and Shared with Potential Vaccine Candidates
by Yadya M. Chawla, Prashant Bajpai, Keshav Saini, Elluri Seetharami Reddy, Ashok Kumar Patel, Kaja Murali-Krishna and Anmol Chandele
Viruses 2024, 16(5), 730; https://doi.org/10.3390/v16050730 (registering DOI) - 05 May 2024
Abstract
As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes [...] Read more.
As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes are known, less is understood about which of these epitopes are conserved among circulating dengue viruses and also shared by potential vaccine candidates. As India emerges as the epicenter of the dengue disease burden and vaccine trials commence in this region, we have here aligned known dengue specific T cell epitopes, reported from other parts of the world with published polyprotein sequences of 107 dengue virus isolates available from India. Of the 1305 CD4 and 584 CD8 epitopes, we found that 24% and 41%, respectively, were conserved universally, whereas 27% and 13% were absent in any viral isolates. With these data, we catalogued epitopes conserved in circulating dengue viruses from India and matched them with each of the six vaccine candidates under consideration (TV003, TDEN, DPIV, CYD-TDV, DENVax and TVDV). Similar analyses with viruses from Thailand, Brazil and Mexico revealed regional overlaps and variations in these patterns. Thus, our study provides detailed and nuanced insights into regional variation that should be considered for itemization of T cell responses during dengue natural infection and vaccine design, testing and evaluation. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
29 pages, 5319 KiB  
Review
Cellulose-Based Hydrogels for Wastewater Treatment: A Focus on Metal Ions Removal
by Francesca Persano, Cosimino Malitesta and Elisabetta Mazzotta
Polymers 2024, 16(9), 1292; https://doi.org/10.3390/polym16091292 (registering DOI) - 05 May 2024
Abstract
The rapid worldwide industrial growth in recent years has made water contamination by heavy metals a problem that requires an immediate solution. Several strategies have been proposed for the decontamination of wastewater in terms of heavy metal ions. Among these, methods utilizing adsorbent [...] Read more.
The rapid worldwide industrial growth in recent years has made water contamination by heavy metals a problem that requires an immediate solution. Several strategies have been proposed for the decontamination of wastewater in terms of heavy metal ions. Among these, methods utilizing adsorbent materials are preferred due to their cost-effectiveness, simplicity, effectiveness, and scalability for treating large volumes of contaminated water. In this context, heavy metal removal by hydrogels based on naturally occurring polymers is an attractive approach for industrial wastewater remediation as they offer significant advantages, such as an optimal safety profile, good biodegradability, and simple and low-cost procedures for their preparation. Hydrogels have the ability to absorb significant volumes of water, allowing for the effective removal of the dissolved pollutants. Furthermore, they can undergo surface chemical modifications which can further improve their ability to retain different environmental pollutants. This review aims to summarize recent advances in the application of hydrogels in the treatment of heavy metal-contaminated wastewater, particularly focusing on hydrogels based on cellulose and cellulose derivatives. The reported studies highlight how the adsorption properties of these materials can be widely modified, with a wide range of adsorption capacity for different heavy metal ions varying between 2.3 and 2240 mg/g. The possibility of developing new hydrogels with improved sorption performances is also discussed in the review, with the aim of improving their effective application in real scenarios, indicating future directions in the field. Full article
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14 pages, 2551 KiB  
Article
Identification of Key Genes of Fruit Shape Variation in Jujube with Integrating Elliptic Fourier Descriptors and Transcriptome
by Yue Ren, Wenqing Fu, Yi Gao, Yuhan Chen, Decang Kong, Ming Cao, Xiaoming Pang and Wenhao Bo
Plants 2024, 13(9), 1273; https://doi.org/10.3390/plants13091273 (registering DOI) - 05 May 2024
Abstract
Jujube (Ziziphus jujuba) exhibits a rich diversity in fruit shape, with natural occurrences of gourd-like, flattened, and other special shapes. Despite the ongoing research into fruit shape, studies integrating elliptical Fourier descriptors (EFDs) with both Short Time-series Expression Miner (STEM) and [...] Read more.
Jujube (Ziziphus jujuba) exhibits a rich diversity in fruit shape, with natural occurrences of gourd-like, flattened, and other special shapes. Despite the ongoing research into fruit shape, studies integrating elliptical Fourier descriptors (EFDs) with both Short Time-series Expression Miner (STEM) and weighted gene co-expression network analysis (WGCNA) for gene discovery remain scarce. In this study, six cultivars of jujube fruits with distinct shapes were selected, and samples were collected from the fruit set period to the white mature stage across five time points for shape analysis and transcriptome studies. By combining EFDs with WGCNA and STEM, the study aimed to identify the critical periods and key genes involved in the formation of jujube fruit shape. The findings indicated that the D25 (25 days after flowering) is crucial for the development of jujube fruit shape. Moreover, ZjAGL80, ZjABI3, and eight other genes have been implicated to regulate the shape development of jujubes at different periods of fruit development, through seed development and fruit development pathway. In this research, EFDs were employed to precisely delineate the shape of jujube fruits. This approach, in conjunction with transcriptome, enhanced the precision of gene identification, and offered an innovative methodology for fruit shape analysis. This integration facilitates the advancement of research into the morphological characteristics of plant fruits, underpinning the development of a refined framework for the genetic underpinnings of fruit shape variation. Full article
(This article belongs to the Special Issue Genetic Breeding of Trees)
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19 pages, 3188 KiB  
Article
meso-Tetrahexyl-7,8-dihydroxychlorin and Its Conversion to ß-Modified Derivatives
by Daniel Aicher, Dinusha Damunupola, Christian B. W. Stark, Arno Wiehe and Christian Brückner
Molecules 2024, 29(9), 2144; https://doi.org/10.3390/molecules29092144 (registering DOI) - 05 May 2024
Abstract
meso-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first meso-alkylporphyrin-based porphyrinoid containing [...] Read more.
meso-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first meso-alkylporphyrin-based porphyrinoid containing a non-pyrrolic building block. Further, the diol chlorin was shown to be susceptible to dehydration, forming the porphyrin enol that is in equilibrium with its keto-chlorin form. The meso-hexylchlorin dione could be reduced and it underwent mono- and bis-methylation reactions using methyl-Grignard reagents, and trifluoromethylation using the Ruppert-Prakash reagent. The optical and spectroscopic properties of the products are discussed and contrasted to their corresponding meso-aryl derivatives (where known). This contribution establishes meso-tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue. Full article
(This article belongs to the Special Issue Porphyrin-Based Compounds: Synthesis and Application, 2nd Edition)
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19 pages, 1471 KiB  
Article
TGF-β2 Induces Ribosome Activity, Alters Ribosome Composition and Inhibits IRES-Mediated Translation in Chondrocytes
by Guus G. H. van den Akker, Alzbeta Chabronova, Bas A. C. Housmans, Laura van der Vloet, Don A. M. Surtel, Andy Cremers, Virginie Marchand, Yuri Motorin, Marjolein M. J. Caron, Mandy J. Peffers and Tim. J. M. Welting
Int. J. Mol. Sci. 2024, 25(9), 5031; https://doi.org/10.3390/ijms25095031 (registering DOI) - 05 May 2024
Abstract
Alterations in cell fate are often attributed to (epigenetic) regulation of gene expression. An emerging paradigm focuses on specialized ribosomes within a cell. However, little evidence exists for the dynamic regulation of ribosome composition and function. Here, we stimulated a chondrocytic cell line [...] Read more.
Alterations in cell fate are often attributed to (epigenetic) regulation of gene expression. An emerging paradigm focuses on specialized ribosomes within a cell. However, little evidence exists for the dynamic regulation of ribosome composition and function. Here, we stimulated a chondrocytic cell line with transforming growth factor beta (TGF-β2) and mapped changes in ribosome function, composition and ribosomal RNA (rRNA) epitranscriptomics. 35S Met/Cys incorporation was used to evaluate ribosome activity. Dual luciferase reporter assays were used to assess ribosomal modus. Ribosomal RNA expression and processing were determined by RT-qPCR, while RiboMethSeq and HydraPsiSeq were used to determine rRNA modification profiles. Label-free protein quantification of total cell lysates, isolated ribosomes and secreted proteins was done by LC-MS/MS. A three-day TGF-β2 stimulation induced total protein synthesis in SW1353 chondrocytic cells and human articular chondrocytes. Specifically, TGF-β2 induced cap-mediated protein synthesis, while IRES-mediated translation was not (P53 IRES) or little affected (CrPv IGR and HCV IRES). Three rRNA post-transcriptional modifications (PTMs) were affected by TGF-β2 stimulation (18S-Gm1447 downregulated, 18S-ψ1177 and 28S-ψ4598 upregulated). Proteomic analysis of isolated ribosomes revealed increased interaction with eIF2 and tRNA ligases and decreased association of eIF4A3 and heterogeneous nuclear ribonucleoprotein (HNRNP)s. In addition, thirteen core ribosomal proteins were more present in ribosomes from TGF-β2 stimulated cells, albeit with a modest fold change. A prolonged stimulation of chondrocytic cells with TGF-β2 induced ribosome activity and changed the mode of translation. These functional changes could be coupled to alterations in accessory proteins in the ribosomal proteome. Full article
(This article belongs to the Special Issue The Evolving Ribosome Concept)
24 pages, 1635 KiB  
Article
Optimal Preventive Maintenance Policy for Equipment Rented under Free Leasing as a Contributor to Sustainable Development
by Lazhar Tlili, Anis Chelbi, Rim Gharyani and Wajdi Trabelsi
Sustainability 2024, 16(9), 3860; https://doi.org/10.3390/su16093860 (registering DOI) - 05 May 2024
Abstract
Leasing has proven to be a business model that is perfectly suited to the circular economy. It significantly contributes to sustainable development by enabling the reuse of machinery and equipment after each lease period and by including preventive maintenance and overhauls within and [...] Read more.
Leasing has proven to be a business model that is perfectly suited to the circular economy. It significantly contributes to sustainable development by enabling the reuse of machinery and equipment after each lease period and by including preventive maintenance and overhauls within and between lease terms. This helps to extend the life cycle of equipment, promote value recovery, and reduce waste. This paper examines an imperfect preventive maintenance (PM) strategy applied to equipment rented under the terms of “free leasing.” In free leasing, the lessor makes the equipment available to the customer for a specified period of time without charging rent. In return, the customer is required to purchase the equipment’s consumables exclusively from the lessor. The lessor is also responsible for the maintenance of the equipment at the customer’s premises. The greater the quantity of consumables used by the customer, the more the equipment will deteriorate. Consequently, the lessor must be able to determine the most effective approach to preventive maintenance, ensuring that it aligns with the customer’s planned usage rate while maximizing profit. This work proposes a PM strategy to be adopted by the lessor during the free lease period. This strategy involves the performance of imperfect PM actions just before the start of the lease period and then periodically. Different packages of preventive actions can be applied each time, with each package having a different cost depending on the level of effectiveness in terms of rejuvenating the equipment. Minimal repairs are performed in the event of equipment failure. The decision variables are the PM period to be adopted and the maintenance efficiency level to be chosen for each preventive intervention. The objective is to determine, for a given customer with an estimated consumption rate profile of consumables, the optimal values of these decision variables so that the lessor maximizes their profit. A mathematical model is developed to express the lessor’s average profit over each lease period. A solution procedure is developed for small instances of the problem, and an Artificial Bee Colony algorithm is implemented for larger instances. A numerical example and a sensitivity analysis are presented. Full article
24 pages, 6931 KiB  
Review
A Case for Trans-Regional Intertidal Research in Unstudied Areas in the Northeast and Southeast Pacific: Filling the Gaps
by Lynn Wilbur, Vasilis Louca, Bruno Ibanez-Erquiaga and Frithjof C. Küpper
Coasts 2024, 4(2), 323-346; https://doi.org/10.3390/coasts4020017 (registering DOI) - 05 May 2024
Abstract
Large areas of the Pacific coast of the Americas remain unstudied regarding their intertidal ecosystems. Given the increasing disturbance related to human impacts on intertidal ecosystems, it is essential to gather census data on the biological composition of poorly studied regions so that [...] Read more.
Large areas of the Pacific coast of the Americas remain unstudied regarding their intertidal ecosystems. Given the increasing disturbance related to human impacts on intertidal ecosystems, it is essential to gather census data on the biological composition of poorly studied regions so that a framework for future monitoring and management can be developed. Here, we synthesize the available research on intertidal communities along the Pacific rim to support the goal to fill bioregional gaps in knowledge in three less-studied areas in Southeast Alaska and Peru. A census of taxonomic and functional group hierarchies in these communities should include the use of various measures of alpha and beta diversity to provide a metric of temporal and spatial comparisons. A narrower-scale approach focusing on foundation species that harbor algal and invertebrate communities and serve as buffers against environmental stresses should also be conducted. Conducting a comprehensive census in poorly studied or unstudied areas will contribute to a better understanding of the response to disturbances caused by oil spills, El Niño and marine heatwaves and provide a latitudinal continuum of scientific knowledge about the biodiversity and ecosystem functioning in rocky intertidal systems on a trans-regional scale. Full article
14 pages, 3400 KiB  
Article
Mitral Cell Dendritic Morphology in the Adult Zebrafish Olfactory Bulb following Growth, Injury and Recovery
by John P. Rozofsky, Joanna M. Pozzuto and Christine A. Byrd-Jacobs
Int. J. Mol. Sci. 2024, 25(9), 5030; https://doi.org/10.3390/ijms25095030 (registering DOI) - 05 May 2024
Abstract
The role of afferent target interactions in dendritic plasticity within the adult brain remains poorly understood. There is a paucity of data regarding the effects of deafferentation and subsequent dendritic recovery in adult brain structures. Moreover, although adult zebrafish demonstrate ongoing growth, investigations [...] Read more.
The role of afferent target interactions in dendritic plasticity within the adult brain remains poorly understood. There is a paucity of data regarding the effects of deafferentation and subsequent dendritic recovery in adult brain structures. Moreover, although adult zebrafish demonstrate ongoing growth, investigations into the impact of growth on mitral cell (MC) dendritic arbor structure and complexity are lacking. Leveraging the regenerative capabilities of the zebrafish olfactory system, we conducted a comprehensive study to address these gaps. Employing an eight-week reversible deafferentation injury model followed by retrograde labeling, we observed substantial morphological alterations in MC dendrites. Our hypothesis posited that cessation of injury would facilitate recovery of MC dendritic arbor structure and complexity, potentially influenced by growth dynamics. Statistical analyses revealed significant changes in MC dendritic morphology following growth and recovery periods, indicating that MC total dendritic branch length retained significance after 8 weeks of deafferentation injury when normalized to individual fish physical characteristics. This suggests that regeneration of branch length could potentially function relatively independently of growth-related changes. These findings underscore the remarkable plasticity of adult dendritic arbor structures in a sophisticated model organism and highlight the efficacy of zebrafish as a vital implement for studying neuroregenerative processes. Full article
(This article belongs to the Special Issue Zebrafish: A Model Organism for Human Health and Disease)
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19 pages, 572 KiB  
Review
The Transorbital Approach: A Comprehensive Review of Targets, Surgical Techniques, and Multiportal Variants
by Matteo De Simone, Cesare Zoia, Anis Choucha, Doo-Sik Kong and Lucio De Maria
J. Clin. Med. 2024, 13(9), 2712; https://doi.org/10.3390/jcm13092712 (registering DOI) - 05 May 2024
Abstract
The transorbital approach (TOA) is gaining popularity in skull base surgery scenarios. This approach represents a valuable surgical corridor to access various compartments and safely address several intracranial pathologies, both intradurally and extradurally, including tumors of the olfactory groove in the anterior cranial [...] Read more.
The transorbital approach (TOA) is gaining popularity in skull base surgery scenarios. This approach represents a valuable surgical corridor to access various compartments and safely address several intracranial pathologies, both intradurally and extradurally, including tumors of the olfactory groove in the anterior cranial fossa (ACF), cavernous sinus in the middle cranial fossa (MCF), and the cerebellopontine angle in the posterior cranial fossa (PCF). The TOA exists in many variants, both from the point of view of invasiveness and from that of the entry point to the orbit, corresponding to the four orbital quadrants: the superior eyelid crease (SLC), the precaruncular (PC), the lateral retrocanthal (LRC), and the preseptal lower eyelid (PS). Moreover, multiportal variants, consisting of the combination of the transorbital approach with others, exist and are relevant to reach peculiar surgical territories. The significance of the TOA in neurosurgery, coupled with the dearth of thorough studies assessing its various applications and adaptations, underscores the necessity for this research. This extensive review delineates the multitude of target lesions reachable through the transorbital route, categorizing them based on surgical complexity. Furthermore, it provides an overview of the different transorbital variations, both standalone and in conjunction with other techniques. By offering a comprehensive understanding, this study aims to enhance awareness and knowledge regarding the current utility of the transorbital approach in neurosurgery. Additionally, it aims to steer future investigations toward deeper exploration, refinement, and exploration of additional perspectives concerning this surgical method. Full article
(This article belongs to the Special Issue State of the Art—Treatment of Skull Base Diseases: Volume II)
14 pages, 7435 KiB  
Article
Influence of Silsesquioxane-Containing Ultra-Thin Polymer Films on Metal Oxide Gas Sensor Performance for the Tunable Detection of Biomarkers
by Oleg Lupan, Mihai Brinza, Julia Piehl, Nicolai Ababii, Nicolae Magariu, Lukas Zimoch, Thomas Strunskus, Thierry Pauporte, Rainer Adelung, Franz Faupel and Stefan Schröder
Chemosensors 2024, 12(5), 76; https://doi.org/10.3390/chemosensors12050076 (registering DOI) - 05 May 2024
Abstract
Certain biomarkers in exhaled breath are indicators of diseases in the human body. The non-invasive detection of such biomarkers in human breath increases the demand for simple and cost-effective gas sensors to replace state-of-the-art gas chromatography (GC) machines. The use of metal oxide [...] Read more.
Certain biomarkers in exhaled breath are indicators of diseases in the human body. The non-invasive detection of such biomarkers in human breath increases the demand for simple and cost-effective gas sensors to replace state-of-the-art gas chromatography (GC) machines. The use of metal oxide (MOX) gas sensors based on thin-film structures solves the current limitations of breath detectors. However, the response at high humidity levels, i.e., in the case of exhaled human breath, significantly decreases the sensitivity of MOX sensors, making it difficult to detect small traces of biomarkers. We have introduced, in previous work, the concept of a hybrid gas sensor, in which thin-film-based MOX gas sensors are combined with an ultra-thin (20–30 nm) polymer top layer deposited by solvent-free initiated chemical vapor deposition (iCVD). The hydrophobic top layer enables sensor measurement in high-humidity conditions as well as the precise tuning of selectivity and sensitivity. In this paper, we present a way to increase the hydrogen (H2) sensitivity of hybrid sensors through chemical modification of the polymer top layer. A poly(1,3,5,7-tetramethyl-tetravinylcyclotetrasiloxane) (PV4D4) thin film, already applied in one of our previous studies, is transformed into a silsesquioxane-containing top layer by a simple heating step. The transformation results in a significant increase in the gas response for H2 ~709% at an operating temperature of 350 °C, which we investigate based on the underlying sensing mechanism. These results reveal new pathways in the biomedical application field for the analysis of exhaled breath, where H2 indicates gastrointestinal diseases. Full article
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17 pages, 1464 KiB  
Article
Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells
by Lynn W. Maines, Staci N. Keller, Ryan A. Smith, Randy S. Schrecengost and Charles D. Smith
Cancers 2024, 16(9), 1779; https://doi.org/10.3390/cancers16091779 (registering DOI) - 05 May 2024
Abstract
Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by [...] Read more.
Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody. Full article
(This article belongs to the Special Issue Targeted Therapy of Pediatric Cancer)
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15 pages, 5985 KiB  
Article
Genome-Wide Identification and Evolutionary Analysis of Receptor-like Kinase Family Genes Provides Insights into Anthracnose Resistance of Dioscorea alata
by Yuqian Jiang, Xin-Yu Lu, Ya-Li Qin, Yan-Mei Zhang and Zhu-Qing Shao
Plants 2024, 13(9), 1274; https://doi.org/10.3390/plants13091274 (registering DOI) - 05 May 2024
Abstract
Dioscorea alata, commonly known as “greater yam”, is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has [...] Read more.
Dioscorea alata, commonly known as “greater yam”, is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance. Full article
(This article belongs to the Special Issue Origin, Evolution and Functional Mechanisms of Plant Immune System)
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11 pages, 424 KiB  
Article
Isolation and Structure Determination of New Pyrones from Dictyostelium spp. Cellular Slime Molds Coincubated with Pseudomonas spp.
by Takehiro Nishimura, Takuya Murotani, Hitomi Sasaki, Yoshinori Uekusa, Hiromi Eguchi, Hirotaka Ishigaki, Katsunori Takahashi, Yuzuru Kubohara and Haruhisa Kikuchi
Molecules 2024, 29(9), 2143; https://doi.org/10.3390/molecules29092143 (registering DOI) - 05 May 2024
Abstract
Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, [...] Read more.
Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, we revealed the structural diversity of secondary metabolites. Cellular slime molds grow by feeding on bacteria, such as Klebsiella aerogenes and Escherichia coli, without using medium components. Although changing the feeding bacteria is expected to affect dramatically the secondary metabolite production, the effect of the feeding bacteria on the production of secondary metabolites is not known. Herein, we report the isolation and structure elucidation of clavapyrone (1) from Dictyostelium clavatum, intermedipyrone (2) from D. magnum, and magnumiol (3) from D. intermedium. These compounds are not obtained from usual cultural conditions with Klebsiella aerogenes but obtained from coincubated conditions with Pseudomonas spp. The results demonstrate the diversity of the secondary metabolites of cellular slime molds and suggest that widening the range of feeding bacteria for cellular slime molds would increase their application potential in drug discovery. Full article
(This article belongs to the Special Issue Discovery of Bioactive Ingredients from Natural Products V)
22 pages, 1327 KiB  
Article
Can Creating an Agro-Product Regional Public Brand Improve the Ability of Farmers to Sustainably Increase Their Revenue?
by Zhiyan Ma and Guanghua Qiao
Sustainability 2024, 16(9), 3861; https://doi.org/10.3390/su16093861 (registering DOI) - 05 May 2024
Abstract
Through the analysis of various typical cases, this study examines whether the establishment of an agro-product regional public brand (ARPB) can effectively boost the revenue of farmers and increase their share in the supply chain. The findings suggest that an early-stage ARPB can [...] Read more.
Through the analysis of various typical cases, this study examines whether the establishment of an agro-product regional public brand (ARPB) can effectively boost the revenue of farmers and increase their share in the supply chain. The findings suggest that an early-stage ARPB can command a price premium for products, yet its overall contribution to farmers’ revenue remains limited due to scale constraints. The premium ability of an ARPB is influenced by product characteristics and sales strategies, underscoring the need to enhance control over terminal sales. Although the revenue of all operators in an ARPB supply chain shows an increase compared to that of a non-ARPB supply chain, the ratios of revenue allocated to farmers diminish. The Shapley value method was utilized to optimize the revenue-sharing in the supply chain, indicating a need to increase the share of revenue for farmers. This optimization necessitates the formation of a community of interests between farmers, processing enterprises, and sellers to facilitate the upstream movement of brand premiums. Furthermore, enhancing the government’s mediation and regulatory functions can provide farmers with more opportunities to partake in brand benefits. Full article
(This article belongs to the Section Sustainable Agriculture)
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14 pages, 1354 KiB  
Systematic Review
The Diagnostic Performance of 2-[18F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis
by Domenico Albano, Alessio Rizzo, Manuela Racca, Barbara Muoio, Francesco Bertagna and Giorgio Treglia
Cancers 2024, 16(9), 1778; https://doi.org/10.3390/cancers16091778 (registering DOI) - 05 May 2024
Abstract
Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission [...] Read more.
Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95%CI: 78.5–93.3), a pooled specificity of 48.1% (95%CI: 27–69.9), a pooled negative predictive value of 90.5% (95%CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95%CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95%CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence. Full article
(This article belongs to the Special Issue Clinical Research Advances in Chronic Lymphocytic Leukemia (CLL))
11 pages, 1955 KiB  
Article
Voltage Control Strategy for Large-Scale Wind Farm with Rapid Wind Speed Fluctuation
by Xi Cai, Zhangbin Yang, Pan Liu, Xueguang Lian, Zhuang Li, Guorong Zhu and Hua Geng
Energies 2024, 17(9), 2220; https://doi.org/10.3390/en17092220 (registering DOI) - 05 May 2024
Abstract
In large-scale wind farms, the voltage fluctuations caused by the uncertainty of wind speed at the turbine terminals pose a pressing challenge. This article presents a localized voltage control strategy tailored toward rapid adjustments in turbine terminal voltage in wind turbine generators. Based [...] Read more.
In large-scale wind farms, the voltage fluctuations caused by the uncertainty of wind speed at the turbine terminals pose a pressing challenge. This article presents a localized voltage control strategy tailored toward rapid adjustments in turbine terminal voltage in wind turbine generators. Based on relative voltage observation, this strategy achieves voltage coordination between the high and low ends of the transformer in wind turbine generators. Firstly, the overall structure of the wind farm and the characteristics of terminal voltage are analyzed. Secondly, the principles and feasibility of the relative voltage control strategy are examined. Finally, the effectiveness of the proposed control strategy is validated through simulation results from a specific wind farm. The results demonstrate its capability to achieve a fast and stable voltage dynamic response within the wind farm based on local information, thus mitigating the risk of voltage out of limit. Full article
(This article belongs to the Section A3: Wind, Wave and Tidal Energy)
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14 pages, 388 KiB  
Article
Fractional Modelling of H2O2-Assisted Oxidation by Spanish broom peroxidase
by Vinh Quang Mai and Thái Anh Nhan
Mathematics 2024, 12(9), 1411; https://doi.org/10.3390/math12091411 (registering DOI) - 05 May 2024
Abstract
The H2O2-assisted oxidation by a peroxidase enzyme takes place to help plants maintain the concentrations of organic compounds at physiological levels. Cells regulate the oxidation rate by inhibiting the action of this enzyme. The cells use two inhibitory processes [...] Read more.
The H2O2-assisted oxidation by a peroxidase enzyme takes place to help plants maintain the concentrations of organic compounds at physiological levels. Cells regulate the oxidation rate by inhibiting the action of this enzyme. The cells use two inhibitory processes to regulate the enzyme: a noncompetitive substrate inhibitory process and a competitive substrate inhibitory process. Numerous applications of peroxidase have been developed in clinical biochemistry, enzyme immunoassays, the treatment of waste water containing phenolic compounds, the synthesis of various aromatic chemicals, and the removal of peroxide from industrial wastes. The kinetic mechanism of the Spanish broom peroxidase enzyme is a Ping Pong Bi Bi mechanism with the presence of competitive inhibition by substrates. A mathematical model may help in identifying the key mechanism from amongst a set of competing mechanisms. In this study, we developed a fractional mathematical model to describe the H2O2-supported oxidation by the enzyme Spanish broom peroxidase. Numerical simulations of the model produced results that are consistent with the known behaviour of Spanish broom peroxidase. Finally, some future investigations of the study are briefly indicated as well. Full article
(This article belongs to the Special Issue Numerical Analysis in Computational Mathematics)
14 pages, 1443 KiB  
Article
Global Receptive Field Designed Complex-Valued Convolutional Neural Network Equalizer for Optical Fiber Communications
by Lu Han, Yongjun Wang, Haifeng Yang, Yang Zhao and Chao Li
Photonics 2024, 11(5), 431; https://doi.org/10.3390/photonics11050431 (registering DOI) - 05 May 2024
Abstract
In this paper, an improved complex-valued convolutional neural network (CvCNN) structure to be placed at the received side is proposed for nonlinearity compensation in a coherent optical system. This complex-valued global convolutional kernel-assisted convolutional neural network equalizer (CvGNN) has been verified in terms [...] Read more.
In this paper, an improved complex-valued convolutional neural network (CvCNN) structure to be placed at the received side is proposed for nonlinearity compensation in a coherent optical system. This complex-valued global convolutional kernel-assisted convolutional neural network equalizer (CvGNN) has been verified in terms of Q-factor performance and complexity compared to seven other related nonlinear equalizers based on both the 64 QAM experimental platform and the QPSK numerical platform. The global convolution operation of the proposed CvGNN is more suitable for the calculation process of perturbation coefficients, and the global receptive field can also be more effective at extracting effective information from perturbation feature maps. The introduction of CvCNN can directly focus on the complex-valued perturbation feature maps themselves without separately processing the real and imaginary parts, which is more in line with the waveform-dependent physical characteristics of optical signals. Based on the experimental platform, compared with the real-valued neural network with small convolutional kernel (RvCNNC), the proposed CvGNNC improves the Q-factor by ∼2.95 dB at the optimal transmission power, while reducing the time complexity by ∼44.7%. Full article
(This article belongs to the Section Optical Communication and Network)
19 pages, 8691 KiB  
Article
Pedestrian Pose Recognition Based on Frequency-Modulated Continuous-Wave Radar with Meta-Learning
by Jiajia Shi, Qiang Zhang, Quan Shi, Liu Chu and Robin Braun
Sensors 2024, 24(9), 2932; https://doi.org/10.3390/s24092932 (registering DOI) - 05 May 2024
Abstract
With the continuous advancement of autonomous driving and monitoring technologies, there is increasing attention on non-intrusive target monitoring and recognition. This paper proposes an ArcFace SE-attention model-agnostic meta-learning approach (AS-MAML) by integrating attention mechanisms into residual networks for pedestrian gait recognition using frequency-modulated [...] Read more.
With the continuous advancement of autonomous driving and monitoring technologies, there is increasing attention on non-intrusive target monitoring and recognition. This paper proposes an ArcFace SE-attention model-agnostic meta-learning approach (AS-MAML) by integrating attention mechanisms into residual networks for pedestrian gait recognition using frequency-modulated continuous-wave (FMCW) millimeter-wave radar through meta-learning. We enhance the feature extraction capability of the base network using channel attention mechanisms and integrate the additive angular margin loss function (ArcFace loss) into the inner loop of MAML to constrain inner loop optimization and improve radar discrimination. Then, this network is used to classify small-sample micro-Doppler images obtained from millimeter-wave radar as the data source for pose recognition. Experimental tests were conducted on pose estimation and image classification tasks. The results demonstrate significant detection and recognition performance, with an accuracy of 94.5%, accompanied by a 95% confidence interval. Additionally, on the open-source dataset DIAT-μRadHAR, which is specially processed to increase classification difficulty, the network achieves a classification accuracy of 85.9%. Full article
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13 pages, 10274 KiB  
Communication
Preliminary Ultrasonographic Study of Healthy California Sea Lion (Zalophus californianus) Pregnancy and Fetal Development
by Letizia Fiorucci, Francesco Grande, Roberto Macrelli and Pietro Saviano
Animals 2024, 14(9), 1384; https://doi.org/10.3390/ani14091384 (registering DOI) - 05 May 2024
Abstract
Reproductive success is an important aspect of marine mammals’ population health, as it is an indicator of the trajectory for the population into the future. The aim of this study is to provide additional relevant data on fetus–maternal ultrasonographic monitoring in sea lion [...] Read more.
Reproductive success is an important aspect of marine mammals’ population health, as it is an indicator of the trajectory for the population into the future. The aim of this study is to provide additional relevant data on fetus–maternal ultrasonographic monitoring in sea lion species, in order to evaluate possible fetal distress or abnormalities. From 2018 to 2023, serial ultrasonographic scans of two healthy California sea lion females (16 ± 4 years old), kept under human care, were performed over the course of two pregnancies for each female. Animals were monitored from the ovulation to the delivery. Ultrasonography was performed weekly, and, during the last month, daily images were recorded using Logiq Versana Active, General Electric, with a 2–5 MHz curvilinear transducer, and Logiq V2, General Electric, with a 2–5 MHz curvilinear transducer. Right and left lateral recumbencies have been used during the examination. To the author’s knowledge, this is the first study describing in detail the sea lion organogenesis and their correlation with the stage of pregnancy. Full article
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28 pages, 500 KiB  
Article
Anisotropic Generalization of the ΛCDM Universe Model with Application to the Hubble Tension
by Øyvind G. Grøn
Symmetry 2024, 16(5), 564; https://doi.org/10.3390/sym16050564 (registering DOI) - 05 May 2024
Abstract
I deduce an exact and analytic Bianchi type I solution of Einstein’s field equations, which generalizes the isotropic ΛCDM universe model to a corresponding model with anisotropic expansion. The main point of the article is to present the anisotropic generalization of the ΛCDM [...] Read more.
I deduce an exact and analytic Bianchi type I solution of Einstein’s field equations, which generalizes the isotropic ΛCDM universe model to a corresponding model with anisotropic expansion. The main point of the article is to present the anisotropic generalization of the ΛCDM universe model in a way suitable for investigating how anisotropic expansion modifies observable properties of the ΛCDM universe model. Although such generalizations of the isotropic ΛCDM universe model have been considered earlier, they have never been presented in this form before. Several physical properties of the model are pointed out and compared with properties of special cases, such as the isotropic ΛCDM universe model. The solution is then used to investigate the Hubble tension. It has recently been suggested that the cosmic large-scale anisotropy may solve the Hubble tension. I consider those earlier suggestions and find that the formulae of these papers lead to the result that the anisotropy of the cosmic expansion is too small to solve the Hubble tension. Then, I investigate the problem in a new way, using the exact solution of the field equations. This gives the result that the cosmic expansion anisotropy is still too small to solve the Hubble tension in the general Bianchi type I universe with dust and LIVE (Lorentz Invariant Vacuum Energy with a constant energy density, which is represented by the cosmological constant) and anisotropic expansion in all three directions—even if one neglects the constraints coming from the requirement that the anisotropy should be sufficiently small so that it does not have any significant effect upon the results coming from the calculations of the comic nucleosynthesis during the first ten minutes of the universe. If this constraint is taken into account, the cosmic expansion anisotropy is much too small to solve the Hubble tension. Full article
(This article belongs to the Special Issue Symmetry in Classical and Quantum Gravity and Field Theory)
19 pages, 352 KiB  
Article
Fractional Stochastic Partial Differential Equations: Numerical Advances and Practical Applications—A State of the Art Review
by Behrouz Parsa Moghaddam, Afshin Babaei, Arman Dabiri and Alexandra Galhano
Symmetry 2024, 16(5), 563; https://doi.org/10.3390/sym16050563 (registering DOI) - 05 May 2024
Abstract
This article aims to provide a comprehensive review of the latest advancements in numerical methods and practical implementations in the field of fractional stochastic partial differential equations (FSPDEs). This type of equation integrates fractional calculus, stochastic processes, and differential equations to model complex [...] Read more.
This article aims to provide a comprehensive review of the latest advancements in numerical methods and practical implementations in the field of fractional stochastic partial differential equations (FSPDEs). This type of equation integrates fractional calculus, stochastic processes, and differential equations to model complex dynamical systems characterized by memory and randomness. It introduces the foundational concepts and definitions essential for understanding FSPDEs, followed by a comprehensive review of the diverse numerical methods and analytical techniques developed to tackle these equations. Then, this article highlights the significant expansion in numerical methods, such as spectral and finite element methods, aimed at solving FSPDEs, underscoring their potential for innovative applications across various disciplines. Full article
(This article belongs to the Section Mathematics)

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