The 2023 MDPI Annual Report has
been released!
 
31 pages, 1559 KiB  
Review
The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency
by George J. Kontoghiorghes
Int. J. Mol. Sci. 2024, 25(9), 4654; https://doi.org/10.3390/ijms25094654 (registering DOI) - 25 Apr 2024
Abstract
The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem [...] Read more.
The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem play major roles in iron metabolism and human physiology. Similarly, the mainstay treatments of the most common diseases of iron metabolism, namely iron deficiency anaemia and iron overload, involve many iron–chelator complexes and the iron-chelating drugs deferiprone (L1), deferoxamine (DF) and deferasirox. Endogenous chelators such as citric acid and glutathione and exogenous chelators such as ascorbic acid also play important roles in iron metabolism and iron homeostasis. Recent advances in the treatment of iron deficiency anaemia with effective iron complexes such as the ferric iron tri-maltol complex (feraccru or accrufer) and the effective treatment of transfusional iron overload using L1 and L1/DF combinations have decreased associated mortality and morbidity and also improved the quality of life of millions of patients. Many other chelating drugs such as ciclopirox, dexrazoxane and EDTA are used daily by millions of patients in other diseases. Similarly, many other drugs or their metabolites with iron-chelation capacity such as hydroxyurea, tetracyclines, anthracyclines and aspirin, as well as dietary molecules such as gallic acid, caffeic acid, quercetin, ellagic acid, maltol and many other phytochelators, are known to interact with iron and affect iron metabolism and related diseases. Different interactions are also observed in the presence of essential, xenobiotic, diagnostic and theranostic metal ions competing with iron. Clinical trials using L1 in Parkinson’s, Alzheimer’s and other neurodegenerative diseases, as well as HIV and other infections, cancer, diabetic nephropathy and anaemia of inflammation, highlight the importance of chelation therapy in many other clinical conditions. The proposed use of iron chelators for modulating ferroptosis signifies a new era in the design of new therapeutic chelation strategies in many other diseases. The introduction of artificial intelligence guidance for optimal chelation therapeutic outcomes in personalised medicine is expected to increase further the impact of chelation in medicine, as well as the survival and quality of life of millions of patients with iron metabolic disorders and also other diseases. Full article
(This article belongs to the Section Molecular Pharmacology)
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13 pages, 1225 KiB  
Article
A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly
by Almudena Morales-Sánchez, José Ignacio Calvo Arenillas, María José Gutiérrez Palmero, José L. Martín-Conty, Begoña Polonio-López, Luís Alonso Dzul López, Laura Mordillo-Mateos, Juan José Bernal-Jiménez, Rosa Conty-Serrano, Francisca Torres-Falguera, Alfonso Martínez Cano and Carlos Durantez-Fernández
J. Clin. Med. 2024, 13(9), 2514; https://doi.org/10.3390/jcm13092514 (registering DOI) - 25 Apr 2024
Abstract
(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent [...] Read more.
(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45–50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed “Up & Go” at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods. Full article
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11 pages, 504 KiB  
Article
Association of Human Papilloma Virus, Cytomegalovirus, and Epstein–Barr Virus with Breast Cancer in Jordanian Women
by Ashraf I. Khasawneh, Nisreen Himsawi, Ashraf Sammour, Sofian Al Shboul, Mohammed Alorjani, Hadeel Al-Momani, Uruk Shahin, Hafez Al-Momani, Moureq R. Alotaibi and Tareq Saleh
Medicina 2024, 60(5), 699; https://doi.org/10.3390/medicina60050699 (registering DOI) - 25 Apr 2024
Abstract
Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) [...] Read more.
Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) in BC samples and to explore their relationship with relevant clinicopathological variables. Materials and Methods: The analysis involved BC samples from 110 Jordanian female patients diagnosed with BC and breast tissue samples from 30 control patients with no evidence of breast malignancy, investigated using real-time PCR. The findings were then correlated with various clinico-pathological characteristics of BC. Results: HPV was detected in 27 (24.5%), CMV in 15 (13.6%), and EBV in 18 (16.4%) BC patients. None of the control samples was positive for HPV or CMV while EBV was detected in only one (3.3%) sample. While (HPV/EBV), (HPV/CMV), and (EBV/CMV) co-infections were reported in 1.8%, 2.7%, and 5.5%, respectively, coinfection with the three viruses (HPV/CMV/EBV) was not reported in our cohort. A statistically significant association was observed between HPV status and age (p = 0.047), and between clinical stage and CMV infection (p = 0.015). Conclusions: Our findings indicate the presence or co-presence of HPV, CMV, and EBV in the BC subpopulation, suggesting a potential role in its development and/or progression. Further investigation is required to elucidate the underlying mechanisms that account for the exact role of oncoviruses in breast carcinogenesis. Full article
(This article belongs to the Section Infectious Disease)
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16 pages, 2519 KiB  
Article
Feature Sparse Choosing VIT Model for Efficient Concrete Crack Segmentation in Portable Crack Measuring Devices
by Xiaohu Zhang, Haifeng Huang and Meng Cai
Electronics 2024, 13(9), 1641; https://doi.org/10.3390/electronics13091641 (registering DOI) - 25 Apr 2024
Abstract
Concrete crack measurement is important for concrete buildings. Deep learning-based segmentation methods have achieved state-of-art results. However, the model size of these models is extremely large which is impossible to use in portable crack measuring devices. To address this problem, a light-weight concrete [...] Read more.
Concrete crack measurement is important for concrete buildings. Deep learning-based segmentation methods have achieved state-of-art results. However, the model size of these models is extremely large which is impossible to use in portable crack measuring devices. To address this problem, a light-weight concrete crack segmentation model based on the Feature Sparse Choosing VIT (LTNet) is proposed by us. In our proposed model, a Feature Sparse Choosing VIT (FSVIT) is used to reduce computational complexity in VIT as well as reducing the number of channels for crack features. In addition, a Feature Channel Selecting Module (FCSM) is proposed by us to reduce channel features as well as suppressing the influence of interfering features. Finally, Depthwise Separable Convolutions are used to substitute traditional convolutions for further reducing computational complexity. As a result, the model size of our LTNet is extremely small. Experimental results show that our LTNet could achieve an accuracy of 0.887, 0.817 and 0.693, and achieve a recall of 0.882, 0.805 and 0.681 on three datasets, respectively, which is 3–8% higher than current mainstream algorithms. However, the model size of our LTNet is only 2 M. Full article
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3 pages, 196 KiB  
Editorial
The Role of Oxidative Stress and Natural Products in Maintaining Human Health
by Hui-Hui Xiao
Nutrients 2024, 16(9), 1268; https://doi.org/10.3390/nu16091268 (registering DOI) - 25 Apr 2024
Abstract
Since 1985, when oxidative stress was first defined as the oxidative damage caused to cells and organs, a large number of studies have shown that oxidative stress is a significant risk factor for various diseases, including tumors [...] Full article
(This article belongs to the Special Issue Oxidative Stress and Protective Effects of Natural Products in Health)
12 pages, 4120 KiB  
Article
Management Efficacy and Response to Post-Application Precipitation of Fungicides for Southern Stem Rot of Peanut and Evaluation of Co-Application with Micronized Sulfur
by Daniel J. Anco, Justin Hiers and Brendan Zurweller
Agronomy 2024, 14(5), 893; https://doi.org/10.3390/agronomy14050893 (registering DOI) - 25 Apr 2024
Abstract
Southern stem rot (SSR) is caused by Athelia rolfsii and is an economically important disease of peanut (Arachis hypogaea L.). Application of protectant fungicides is an effective management component for reducing levels of this soil-borne disease. The majority of peanut hectarage in [...] Read more.
Southern stem rot (SSR) is caused by Athelia rolfsii and is an economically important disease of peanut (Arachis hypogaea L.). Application of protectant fungicides is an effective management component for reducing levels of this soil-borne disease. The majority of peanut hectarage in South Carolina and Mississippi is rainfed. Timely precipitation has the potential to aid the movement of foliar-applied fungicides through the canopy and into contact with soil interfaces where SSR infections occur. Questions have arisen as to the quantitative relationship of post-application precipitation and fungicide-active ingredient efficacy in managing SSR and protecting associated pod yield potentials. To examine this, fungicide efficacy experiments were screened for inclusion in a meta-analysis, from which eleven experiments conducted from 2015 to 2023 were selected and paired with environmental data from nearby weather stations. Precipitation during the two days following fungicide application was associated with significant reduction in SSR incidence (logit rate of −0.0039/mm) and increased pod yield (log slope of 0.0028/mm). Active ingredient interactions with precipitation among pod yield but not SSR incidence data were present for benzovindiflupyr plus azoxystrobin, flutolanil, and tebuconazole. Fungicides with the greatest levels of control per application at maximum label rates were inpyrfluxam (18.8%), benzovindiflupyr plus azoxystrobin (15.4%), flutolanil (12.3%), and prothioconazole plus tebuconazole (10.5%). Micronized sulfur neither contributed to SSR control nor pod yield increase. Tebuconazole was associated with the greatest % SSR control per fungicide product cost (0.47%/$/ha/application) but was also the treatment with the least amount of control (3.5%) at its maximum label rate. Maximum label rates of benzovindiflupyr plus azoxystrobin (USD 637) and inpyrfluxam (USD 548) were estimated as conferring the greatest returns over the chlorothalonil-only control. Results serve as a helpful reference for farmers and practitioners in selecting fungicide management options and targeting application times, as feasible, to utilize natural precipitation to improve management outcomes. Full article
(This article belongs to the Special Issue Pest Control Technologies Applied in Peanut Production Systems)
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18 pages, 25034 KiB  
Article
Single-Image Super-Resolution Method for Rotating Synthetic Aperture System Using Masking Mechanism
by Yu Sun, Xiyang Zhi, Shikai Jiang, Tianjun Shi, Jiachun Song, Jiawei Yang, Shengao Wang and Wei Zhang
Remote Sens. 2024, 16(9), 1508; https://doi.org/10.3390/rs16091508 (registering DOI) - 25 Apr 2024
Abstract
The emerging technology of rotating synthetic aperture (RSA) presents a promising solution for the development of lightweight, large-aperture, and high-resolution optical remote sensing systems in geostationary orbit. However, the rectangular shape of the primary mirror and the distinctive imaging mechanism involving the continuous [...] Read more.
The emerging technology of rotating synthetic aperture (RSA) presents a promising solution for the development of lightweight, large-aperture, and high-resolution optical remote sensing systems in geostationary orbit. However, the rectangular shape of the primary mirror and the distinctive imaging mechanism involving the continuous rotation of the mirror lead to a pronounced decline in image resolution along the shorter side of the rectangle compared to the longer side. The resolution also exhibits periodic time-varying characteristics. To address these limitations and enhance image quality, we begin by analyzing the imaging mechanism of the RSA system. Subsequently, we propose a single-image super-resolution method that utilizes a rotated varied-size window attention mechanism instead of full attention, based on the Vision Transformer architecture. We employ a two-stage training methodology for the network, where we pre-train it on images masked with stripe-shaped masks along the shorter side of the rectangular pupil. Following that, we fine-tune the network using unmasked images. Through the strip-wise mask sampling strategy, this two-stage training approach effectively circumvents the interference of lower confidence (clarity) information and outperforms training the network from scratch using the unmasked degraded images. Our digital simulation and semi-physical imaging experiments demonstrate that the proposed method achieves satisfactory performance. This work establishes a valuable reference for future space applications of the RSA system. Full article
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22 pages, 5512 KiB  
Article
The Potential Antinociceptive Effect and Mechanism of Cannabis sativa L. Extract on Paclitaxel-Induced Neuropathic Pain in Rats Uncovered by Multi-Omics Analysis
by Yunhui Xu, Lijuan Yao, Yuhan Guo, Chenfeng Shi, Jing Zhou and Moli Hua
Molecules 2024, 29(9), 1958; https://doi.org/10.3390/molecules29091958 (registering DOI) - 25 Apr 2024
Abstract
Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated [...] Read more.
Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand–receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand–receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN. Full article
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13 pages, 3301 KiB  
Article
Geological and Geotechnical Aspects of the Most Significant Deep Landslides in the Danube Area on the Territory of Vojvodina
by Mitar Djogo, Milinko Vasić, Iva Despotović and Stefan Mihajlović
Appl. Sci. 2024, 14(9), 3622; https://doi.org/10.3390/app14093622 (registering DOI) - 25 Apr 2024
Abstract
The largest and the deepest landslides in Serbia occurred on the right valley side of the Danube. General conclusions about landslides along the Danube were obtained on the basis of their comprehensive, detailed investigations: the Sloboda bridge in Novi Sad, the Beška bridge, [...] Read more.
The largest and the deepest landslides in Serbia occurred on the right valley side of the Danube. General conclusions about landslides along the Danube were obtained on the basis of their comprehensive, detailed investigations: the Sloboda bridge in Novi Sad, the Beška bridge, the large settlement of Bocke, and the high-speed railway viaduct in Čortanovci. These areas are actually large, unstable slopes with deep and shallow landslides. Deep landslides consist of several sliding blocks with 20–40 m in depth. All these landslides were formed in clays and sands of the Pliocene age in the decayed crust of these sediments. The general conclusions about landslides presented in this paper will be of great use for the construction of new facilities in the entire unstable area along the Danube, which is about 100 km in length. Full article
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15 pages, 1867 KiB  
Review
The Role of the Host Cytoskeleton in the Formation and Dynamics of Rotavirus Viroplasms
by Janine Vetter, Melissa Lee and Catherine Eichwald
Viruses 2024, 16(5), 668; https://doi.org/10.3390/v16050668 (registering DOI) - 25 Apr 2024
Abstract
Rotavirus (RV) replicates within viroplasms, membraneless electron-dense globular cytosolic inclusions with liquid–liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, [...] Read more.
Rotavirus (RV) replicates within viroplasms, membraneless electron-dense globular cytosolic inclusions with liquid–liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single- and double-stranded virus RNAs, and host components such as microtubules, perilipin-1, and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell. Full article
(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)
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19 pages, 4002 KiB  
Article
Development and Application of an IoT-Based System for Soil Water Status Monitoring in a Soil Profile
by Alessandro Comegna, Shawcat Basel Mostafa Hassan and Antonio Coppola
Sensors 2024, 24(9), 2725; https://doi.org/10.3390/s24092725 (registering DOI) - 25 Apr 2024
Abstract
Soil water content (θ), matric potential (h) and hydraulic conductivity (K) are key parameters for hydrological and environmental processes. Several sensors have been developed for measuring soil θ–hK relationships. The cost of such commercially available sensors [...] Read more.
Soil water content (θ), matric potential (h) and hydraulic conductivity (K) are key parameters for hydrological and environmental processes. Several sensors have been developed for measuring soil θ–hK relationships. The cost of such commercially available sensors may vary over several orders of magnitude. In recent years, some sensors have been designed in the framework of Internet of Things (i.e., IoT) systems to make remote real-time soil data acquisition more straightforward, enabling low-cost field-scale monitoring at high spatio-temporal scales. In this paper, we introduce a new multi-parameter sensor designed for the simultaneous estimation of θ and h at different soil depths and, due to the sensor’s specific layout, the soil hydraulic conductivity function via the instantaneous profile method (IPM). Our findings indicate that a second-order polynomial function is the most suitable model (R2 = 0.99) for capturing the behavior of the capacitive-based sensor in estimating θ in the examined soil, which has a silty-loam texture. The effectiveness of low-cost capacitive sensors, coupled with the IPM method, was confirmed as a viable alternative to time domain reflectometry (TDR) probes. Notably, the layout of the sensor makes the IPM method less labor-intensive to implement. The proposed monitoring system consistently demonstrated robust performance throughout extended periods of data acquisition and is highly suitable for ongoing monitoring of soil water status. Full article
(This article belongs to the Section Environmental Sensing)
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21 pages, 3142 KiB  
Review
Current Status of and Suggestions on Sewage Treatment Fees in China
by Guoming Zeng, Zilong Ma, Yu He, Lin Chen, Da Sun and Xiaoling Lei
Water 2024, 16(9), 1219; https://doi.org/10.3390/w16091219 (registering DOI) - 25 Apr 2024
Abstract
China’s sewage treatment standards have been gradually improving, yet there is a widening gap between sewage treatment fees and actual costs. This discrepancy, where the fees for sewage treatment are lower than the actual operational expenses, poses a significant bottleneck to the sustainable [...] Read more.
China’s sewage treatment standards have been gradually improving, yet there is a widening gap between sewage treatment fees and actual costs. This discrepancy, where the fees for sewage treatment are lower than the actual operational expenses, poses a significant bottleneck to the sustainable development of China’s sewage treatment industry. As a core aspect of environmental economic policies, sewage treatment fees are pivotal in regulating water pollution emissions and addressing water resource shortages. Currently, there are major issues with sewage treatment fees, including an incomplete pricing system, insufficient fees, unclear fee distribution, and a heavy reliance on local finances. These problems impede systematic planning, diminish management efficiency, and hinder the sustainable development of the sewage treatment industry. Thus, future research efforts should prioritize the establishment of a pricing mechanism that comprehensively covers the full cost of sewage treatment. This article presents a concise summary and review of the current situation, types of fee collection, cost accounting methodologies, challenges, and proposed countermeasures for sewage treatment fees, and could serve as a relevant reference for future research on sewage treatment fees. By comprehensively addressing these issues, the sewage treatment industry would progress towards healthier and more sustainable development, ultimately achieving the goal of green growth. Full article
(This article belongs to the Section Wastewater Treatment and Reuse)
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14 pages, 2451 KiB  
Article
Hardware Acceleration of Digital Pulse Shape Analysis Using FPGAs
by César González, Mariano Ruiz, Antonio Carpeño, Alejandro Piñas, Daniel Cano-Ott, Julio Plaza, Trino Martinez and David Villamarin
Sensors 2024, 24(9), 2724; https://doi.org/10.3390/s24092724 (registering DOI) - 25 Apr 2024
Abstract
The BC501A sensor is a liquid scintillator frequently used in nuclear physics for detecting fast neutrons. This paper describes a hardware implementation of digital pulse shape analysis (DPSA) for real-time analysis. DPSA is an algorithm that extracts the physically relevant parameters from the [...] Read more.
The BC501A sensor is a liquid scintillator frequently used in nuclear physics for detecting fast neutrons. This paper describes a hardware implementation of digital pulse shape analysis (DPSA) for real-time analysis. DPSA is an algorithm that extracts the physically relevant parameters from the detected BC501A signals. The hardware solution is implemented in a MicroTCA system that provides the physical, mechanical, electrical, and cooling support for an AMC board (NAMC-ZYNQ-FMC) with a Xilinx ZYNQ Ultrascale-MP SoC. The Xilinx FPGA programmable logic implements a JESD204B interface to high-speed ADCs. The physical and datalink JESD204B layers are implemented using hardware description language (HDL), while the Xilinx high-level synthesis language (HLS) is used for the transport and application layers. The DPSA algorithm is a JESD204B application layer that includes a FIR filter and a constant fraction discriminator (CFD) function, a baseline calculation function, a peak detection function, and an energy calculation function. This architecture achieves an analysis mean time of less than 100 µs per signal with an FPGA resource utilization of about 50% of its most used resources. This paper presents a high-performance DPSA embedded system that interfaces with a 1 GS/s ADC and performs accurate calculations with relatively low latency. Full article
(This article belongs to the Special Issue Advanced Interface Circuits for Sensor Systems (Volume II))
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16 pages, 3876 KiB  
Article
In Silico Prediction of New Inhibitors for Kirsten Rat Sarcoma G12D Cancer Drug Target Using Machine Learning-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulation Approaches
by Amar Ajmal, Muhammad Danial, Maryam Zulfat, Muhammad Numan, Sidra Zakir, Chandni Hayat, Khulood Fahad Alabbosh, Magdi E. A. Zaki, Arif Ali and Dongqing Wei
Pharmaceuticals 2024, 17(5), 551; https://doi.org/10.3390/ph17050551 (registering DOI) - 25 Apr 2024
Abstract
Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is [...] Read more.
Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery)
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13 pages, 2230 KiB  
Article
Sensing and Microbiological Activity of a New Blue Fluorescence Polyamidoamine Dendrimer Modified with 1,8-Naphthalimide Units
by Ivo Grabchev, Albena Jordanova, Evgenia Vasileva-Tonkova and Ivan L. Minkov
Molecules 2024, 29(9), 1960; https://doi.org/10.3390/molecules29091960 (registering DOI) - 25 Apr 2024
Abstract
A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue [...] Read more.
A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb2+, Zn2+, Mg2+, Sn2+, Ba2+, Ni2+, Sn2+, Mn2+, Co2+, Fe3+, and Al3+) was also investigated, and it was found that in the presence of Fe3+, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive B. cereus and Gram-negative P. aeruginosa. The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and B. cereus was found slightly more sensitive than P. aeruginosa. The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes. Full article
(This article belongs to the Special Issue Advances in Fluorescent Probe Technology)
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12 pages, 1390 KiB  
Article
Distributed Consensus for Global Matrix Formation in the Principal Component Pursuit Scenario
by Gustavo Suárez  and Juan David Velásquez
Appl. Sci. 2024, 14(9), 3619; https://doi.org/10.3390/app14093619 (registering DOI) - 25 Apr 2024
Abstract
The aim behind principal component pursuit is to recover a low-rank matrix and a sparse matrix from a noisy signal which is the sum of both matrices. This optimization problem is a priori and non-convex and is useful in signal processing, data compression, [...] Read more.
The aim behind principal component pursuit is to recover a low-rank matrix and a sparse matrix from a noisy signal which is the sum of both matrices. This optimization problem is a priori and non-convex and is useful in signal processing, data compression, image processing, machine learning, fluid dynamics, and more. Here, a distributed scheme described by a static undirected graph, where each agent only observes part of the noisy or corrupted matrix, is applied to achieve a consensus; then, a robust approach that can also handle missing values is applied using alternating directions to solve the convex relaxation problem, which actually solves the non-convex problem under some weak assumptions. Some examples of image recovery are shown, where the network of agents achieves consensus exponentially fast. Full article
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11 pages, 1078 KiB  
Article
Associations between Corneal Nerve Structure and Function in a Veteran Population
by Mohammad Ayoubi, Kimberly Cabrera, Elyana VT Locatelli, Elizabeth R. Felix and Anat Galor
J. Clin. Med. 2024, 13(9), 2513; https://doi.org/10.3390/jcm13092513 (registering DOI) - 25 Apr 2024
Abstract
Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires [...] Read more.
Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (β = −0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function. Full article
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16 pages, 7082 KiB  
Article
Research on an Alpha Navigation Signal Detection Method Based on Multichannel Orthogonal Correlation
by Wenhe Yan, Shifeng Li, Xinze Ma, Yuhang Song, Jiangbin Yuan and Yu Hua
Appl. Sci. 2024, 14(9), 3620; https://doi.org/10.3390/app14093620 (registering DOI) - 25 Apr 2024
Abstract
The Alpha navigation system is the only operating radio system based on very-low-frequency (VLF) signals that can be used to research VLF navigation, timing, and ionospheric characteristics. The detection of the Alpha navigation signal is the key step in the Alpha receiver; however, [...] Read more.
The Alpha navigation system is the only operating radio system based on very-low-frequency (VLF) signals that can be used to research VLF navigation, timing, and ionospheric characteristics. The detection of the Alpha navigation signal is the key step in the Alpha receiver; however, the received Alpha navigation signal is susceptible to noise and mutual interference, which deteriorates signal detection performance. This paper presents a multichannel orthogonal correlation method for Alpha navigation signal detection. Once the three frequency signals of the Alpha navigation system are obtained using a notch filter, station identification is realized using a multichannel orthogonal correlation method and signal format. The selection of key parameters and the detection performance under noise and mutual interference are analyzed. This method’s detection probability exceeds 90% when the signal-to-noise ratio (SNR) is greater than −10 dB. The influence of mutual interference on the signal correlation peak is less than 1% when the signal-to-interference ratio (SIR) of the mutual interference is greater than −28 dB. The proposed method is verified using an actual signal collected using an Alpha receiver. The results show that an Alpha signal can be detected at an extremely low SNR. This method has strong practicability and satisfies the application requirements of an Alpha receiver. Full article
(This article belongs to the Special Issue Signal Acquisition and Processing for Measurement and Testing)
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17 pages, 2504 KiB  
Article
Using Quinolin-4-Ones as Convenient Common Precursors for a Metal-Free Total Synthesis of Both Dubamine and Graveoline Alkaloids and Diverse Structural Analogues
by Rodrigo Abonia, Lorena Cabrera, Diana Arteaga, Daniel Insuasty, Jairo Quiroga, Paola Cuervo and Henry Insuasty
Molecules 2024, 29(9), 1959; https://doi.org/10.3390/molecules29091959 (registering DOI) - 25 Apr 2024
Abstract
The Rutaceae family is one of the most studied plant families due to the large number of alkaloids isolated from them with outstanding biological properties, among them the quinoline-based alkaloids Graveoline 1 and Dubamine 2. The most common methods for the synthesis [...] Read more.
The Rutaceae family is one of the most studied plant families due to the large number of alkaloids isolated from them with outstanding biological properties, among them the quinoline-based alkaloids Graveoline 1 and Dubamine 2. The most common methods for the synthesis of alkaloids 1 and 2 and their derivatives involves cycloaddition reactions or metal-catalyzed coupling processes but with some limitations in scope and functionalization of the quinoline moiety. As a continuation of our current studies on the synthesis and chemical transformation of 2-aminochalcones, we are reporting here an efficient metal-free approach for the total synthesis of alkaloids 1 and 2 along with their analogues with structural diversity, through a two-step sequence involving intramolecular cyclization, oxidation/aromatization, N-methylation and oxidative C-C bond processes, starting from dihydroquinolin-4-ones as common precursors for the construction of the structures of both classes of alkaloids. Full article
(This article belongs to the Special Issue Advances in Heterocyclic Synthesis)
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19 pages, 2538 KiB  
Article
Validation of a New Duplex Real-Time Polymerase Chain Reaction for Chlamydia trachomatis DNA Detection in Ocular Swab Samples
by Joana da Felicidade Ribeiro Favacho, Keren Kariene Leite, Thiago Jacomasso, Aline Burda Farias, Luciano Chaves Franco Filho, Samara Tatielle Monteiro Gomes, Herald Souza dos Reis, Gardene Dourado Mota, Pedro Henrique de Caires Schluga, Walleyd Sami Tassi, Rita de Cássia Pontello Rampazzo, Sheila Kay West, Charlotte Ann Gaydos, Antonio José Ledo Alves da Cunha and Alexandre Dias Tavares Costa
Diagnostics 2024, 14(9), 892; https://doi.org/10.3390/diagnostics14090892 (registering DOI) - 25 Apr 2024
Abstract
Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. [...] Read more.
Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal. Full article
(This article belongs to the Special Issue Microbiology Laboratory: Sample Collection and Diagnosis Advances)
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13 pages, 1961 KiB  
Article
Organic vs. Integrated-Production Agriculture Farming: Which Grapevine Stress-Responsive Genes Are Affected by the Application of Resistance Inducers and Elicitors?
by Tomás Monteiro, Mariana Patanita, Maria do Rosário Félix, André Albuquerque, Joana A. Ribeiro, Filipa Santos, Margarida Basaloco, Augusto Maria da Rosa and Maria Doroteia Campos
Agronomy 2024, 14(5), 892; https://doi.org/10.3390/agronomy14050892 (registering DOI) - 25 Apr 2024
Abstract
With the rising prominence of organic farming systems in European Union countries, motivated by agricultural policies, there is pressure for effective disease management strategies. To address this challenge, the use of plant resistance inducers (PRIs) and elicitors has emerged as a promising approach. [...] Read more.
With the rising prominence of organic farming systems in European Union countries, motivated by agricultural policies, there is pressure for effective disease management strategies. To address this challenge, the use of plant resistance inducers (PRIs) and elicitors has emerged as a promising approach. In this study, we compared the impact of integrated production with organic agriculture farming practices, specifically applying PRIs and elicitors in the latter, on the expression levels of stress-responsive genes in two grapevine cultivars, ‘Alicante Bouschet’ and ‘Trincadeira’. Our findings revealed that the organic farming system led to upregulation of eight of the 12 studied genes in at least one cultivar, indicating a significant influence of production mode. The upregulated genes were associated with plant stress-responsive genes (PR1, PR2, PR4, and TLP9), sugar metabolism (HT5), phenylpropanoids (STS1), enzymes related to jasmonic acid synthesis and response to biotic stresses, respectively (LOX, PER42). Also, the ‘Alicante Bouschet’ cultivar consistently displayed significantly higher levels of transcript accumulation on most of the stress-related genes compared to the ‘Trincadeira’ cultivar in both production modes. Our study provides valuable insights into the effectiveness of PRIs and elicitors in increasing plant expression levels of stress-responsive genes, leading to greater resilience to pathogen attacks and emphasizing their position in organic agriculture. Full article
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12 pages, 3050 KiB  
Article
Analytical Pyrolysis of Soluble Bio-Tar from Steam Pretreatment of Bamboo by Using TG–FTIR and Py–GC/MS
by Yongshun Feng, Xin Pan, Hui Qiao and Xiaowei Zhuang
Materials 2024, 17(9), 1985; https://doi.org/10.3390/ma17091985 (registering DOI) - 25 Apr 2024
Abstract
Steam pretreatment at high temperatures enables fresh bamboo to possess antifungal and antiseptic properties. The process produces a large amount of wastewater that urgently needs to be recycled. Soluble bio-tars derived from wastewater under low-temperature (LTS-tar) and high-temperature (HTS-tar) steam pretreatments of moso [...] Read more.
Steam pretreatment at high temperatures enables fresh bamboo to possess antifungal and antiseptic properties. The process produces a large amount of wastewater that urgently needs to be recycled. Soluble bio-tars derived from wastewater under low-temperature (LTS-tar) and high-temperature (HTS-tar) steam pretreatments of moso bamboo were studied with a thermogravimetric analyzer coupled with Fourier transform infrared spectroscopy (TG–FTIR) and pyrolysis–gas-chromatography/mass spectrometry (Py–GC/MS). Thermogravimetric analysis showed that in the three stages of the thermal decomposition process, the final residue of the bamboo and HTS-tar had two main peaks of 0.88 wt% and 6.85 wt%. The LTS-tar had much more complicated thermal decomposition behavior, with six steps and a high residue yield of 23.86 wt%. A large quantity of CH4 was observed at the maximum mass loss rates of the bamboo and bio-tars. Acids, aldehydes, ketones, esters, and phenolic compounds were found in the pyrolysis products of the bamboo and soluble bio-tars. Both bio-tars contained carbohydrates and lignin fragments, but the LTS-tar under mild steam conditions had more saccharides and was much more sensitive to temperature. The lignin in the bamboo degraded under harsh steam conditions, resulting in high aromatic and polymeric features for the HTS-tar. The significant differences between LTS-tar and HTS-tar require different techniques to achieve the resource utilization of wastewater in the bamboo industry. Full article
(This article belongs to the Section Biomaterials)
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15 pages, 293 KiB  
Review
Prostate-Specific Membrane Antigen-Targeted Therapy in Prostate Cancer: History, Combination Therapies, Trials, and Future Perspective
by Francesco Mattana, Lorenzo Muraglia, Antonio Barone, Marzia Colandrea, Yasmina Saker Diffalah, Silvia Provera, Alfio Severino Cascio, Emanuela Omodeo Salè and Francesco Ceci
Cancers 2024, 16(9), 1643; https://doi.org/10.3390/cancers16091643 (registering DOI) - 25 Apr 2024
Abstract
In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, [...] Read more.
In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [177Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [177Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [177Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa. Full article

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