The 2023 MDPI Annual Report has
been released!
 
12 pages, 763 KiB  
Article
Prion Seeding Activity in Plant Tissues Detected by RT-QuIC
by Kate Burgener, Stuart Siegfried Lichtenberg, Daniel P. Walsh, Heather N. Inzalaco, Aaron Lomax and Joel A. Pedersen
Pathogens 2024, 13(6), 452; https://doi.org/10.3390/pathogens13060452 (registering DOI) - 26 May 2024
Abstract
Prion diseases such as scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) affect domesticated and wild herbivorous mammals. Animals afflicted with CWD, the transmissible spongiform encephalopathy of cervids (deer, elk, and moose), shed prions into the environment, where they may persist [...] Read more.
Prion diseases such as scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) affect domesticated and wild herbivorous mammals. Animals afflicted with CWD, the transmissible spongiform encephalopathy of cervids (deer, elk, and moose), shed prions into the environment, where they may persist and remain infectious for years. These environmental prions may remain in soil, be transported in surface waters, or assimilated into plants. Environmental sampling is an emerging area of TSE research and can provide more information about prion fate and transport once shed by infected animals. In this study, we have developed the first published method for the extraction and detection of prions in plant tissue using the real-time quaking-induced conversion (RT-QuIC) assay. Incubation with a zwitterionic surfactant followed by precipitation with sodium phosphotungstate concentrates the prions within samples and allows for sensitive detection of prion seeding activity. Using this protocol, we demonstrate that prions can be detected within plant tissues and on plant surfaces using the RT-QuIC assay. Full article
(This article belongs to the Special Issue Advances in Chronic Wasting Disease)
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13 pages, 3698 KiB  
Article
Climate–Growth Relationships of Mongolian Pine (Pinussylvestris var. mongholica) along an Altitudinal Gradient of Northeast China
by Xinrui Wang, Zhaopeng Wang, Dongyou Zhang, Taoran Luo, Xiangyou Li, Bingyun Du and Shubing Zhong
Forests 2024, 15(6), 922; https://doi.org/10.3390/f15060922 (registering DOI) - 26 May 2024
Abstract
To study the radial growth of Mongolian pine (Pinus sylvestris var. mongholica, MP) trees in response to climatic factors against the global warming background in the northeast part of the Greater Khingan Mountains (GKM), 101 tree cores were collected at contrasting altitudes [...] Read more.
To study the radial growth of Mongolian pine (Pinus sylvestris var. mongholica, MP) trees in response to climatic factors against the global warming background in the northeast part of the Greater Khingan Mountains (GKM), 101 tree cores were collected at contrasting altitudes (1100 and 650 m) in the Mordoga area, a tree-ring width chronology of MP was established for that region at both altitudes, and the relation between climatic factors and ring width trends at different time scales was investigated. The results revealed four major findings. (1) The ring width chronology of MP in the low-altitude area has better quality. (2) The growth of MP at high (low) altitude was mainly influenced by temperature (precipitation) factors. (3) Before a sudden change in temperature, there was a decreasing trend in the annual indices of MPs at higher altitudes. The chronological coefficients of MPs at both altitudes showed a significant upward trend after the increase in temperature. (4) The sliding analysis results showed that the stability of the relationship between MP growth and its response to climatic factors at both altitudes was also mostly similar. MP growth is relatively stable and sensitive and to climatic factors as temperatures increase. Full article
(This article belongs to the Section Forest Meteorology and Climate Change)
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11 pages, 271 KiB  
Article
COVID-19 Posttraumatic Stress Disorder and Mental Health among Spanish Adolescents: SESSAMO Project
by Nora Yárnoz-Goñi, Adriana Goñi-Sarriés, Azucena Díez-Suárez, Guillermo Pírez, Leticia Morata-Sampaio and Almudena Sánchez-Villegas
J. Clin. Med. 2024, 13(11), 3114; https://doi.org/10.3390/jcm13113114 (registering DOI) - 26 May 2024
Abstract
Background: Child and adolescent mental health problems have increased after the COVID-19 pandemic. The objective of this study was to establish the association of the presence and intensity of posttraumatic stress due to COVID-19 with the presence of (1) self-harm and suicide [...] Read more.
Background: Child and adolescent mental health problems have increased after the COVID-19 pandemic. The objective of this study was to establish the association of the presence and intensity of posttraumatic stress due to COVID-19 with the presence of (1) self-harm and suicide risk, (2) depressive and anxious symptoms, (3) eating disorders and (4) problematic Internet and video game use. Methods: A cross-sectional analysis was performed on a sample of second–fourth grade secondary school students (14 to 16 years old) from Navarra and the Canary Islands recruited at the SESSAMO project. Validated questionnaires were used to assess the intensity of posttraumatic stress due to COVID-19, risk of suicide and presence of self-harm, symptoms of mental disorder and problematic use of the Internet and video games. Results: Out of 1423 participants analyzed, those with the highest level of posttraumatic stress showed a significant increase in the risk of suicide (OR = 5.18; 95% CI = 2.96–9.05) and in the presence of eating disorder symptoms (OR = 3.93; 95% CI = 2.21–7.00), and higher anxiety and depression scores (b coefficient for anxiety = 11.1; CI = 9.7–12.5; for depression = 13.0; CI = 11.5–14.5) as compared to those with the lowest level. Participants with a high level of posttraumatic stress were almost 10 times more likely to present problematic video game use (OR = 9.49; 95% CI = 3.13–28.82). Conclusions: Years after the pandemic, posttraumatic stress derived from it continues to impact the mental health of adolescents. Further long-term research is needed, as well as close follow-up and intervention in this population. Full article
20 pages, 10885 KiB  
Article
On a Composite Obtained by Thermolysis of Cu-Doped Glycine
by Pedro Chamorro-Posada, Roberto C. Dante, Jesús Martín-Gil, Denisse G. Dante, Alma Cioci, José Vázquez-Cabo, Óscar Rubiños-López, Irene Mediavilla-Martínez and Pablo Martín-Ramos
C 2024, 10(2), 49; https://doi.org/10.3390/c10020049 (registering DOI) - 26 May 2024
Abstract
Metal-doped carbonaceous materials have garnered significant attention in recent years due to their versatile applications in various fields, including catalysis, energy storage, environmental remediation, electronics, and sensors, as well as reinforcement. This study investigates the synthesis and characterization of a composite material featuring [...] Read more.
Metal-doped carbonaceous materials have garnered significant attention in recent years due to their versatile applications in various fields, including catalysis, energy storage, environmental remediation, electronics, and sensors, as well as reinforcement. This study investigates the synthesis and characterization of a composite material featuring a carbonaceous matrix doped with copper, focusing on the thermolysis of glycine as a precursor. The synthesis methodology involved utilizing glycine and copper acetate monohydrate in varying ratios, with the mixture subjected to heating in ceramic crucibles at temperatures ranging from 450 to 550 °C, with pyrolysis yields over the 5 to 39% interval. The pristine and Cu-doped samples obtained at 500 °C underwent characterization using a diverse array of techniques, including scanning and transmission electron microscopies, multi-elemental analysis by energy dispersive X-ray spectroscopy, CHNS elemental analysis, X-ray photoelectron spectroscopy, X-ray powder diffraction, infrared and Raman spectroscopies, ultraviolet-visible spectroscopy, and terahertz time-domain spectroscopy, along with conductivity measurements. Under optimized conditions, copper (at 6.5%) was present primarily in the free metallic form, accompanied by traces of tenorite (CuO) and cuprite (Cu2O). The carbonaceous matrix exhibited a 6:1 ratio of graphitic carbon to a carbon-nitrogen compound with the formula C2H2N2O2, such as isomers of diazetidinedione, according to multi-elemental analysis results. Conductivity measurements disclosed a significant increase in conductivity compared to the product of glycine thermolysis, showcasing the enhanced electrical properties of the new composite. Additionally, terahertz measurements showed the potential of the material as a broadband absorber for the fabrication of terahertz devices and provided compelling evidence of a significant improvement in radiation absorption upon copper doping. In conclusion, this research sheds light on the promising properties of copper-doped carbonaceous composites obtained by glycine pyrolysis, offering insights into their potential applications in emerging technological domains. Full article
(This article belongs to the Section Carbon Materials and Carbon Allotropes)
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15 pages, 810 KiB  
Article
Eight Weeks of Intermittent Exercise in Hypoxia, with or without a Low-Carbohydrate Diet, Improves Bone Mass and Functional and Physiological Capacity in Older Adults with Type 2 Diabetes
by Raquel Kindlovits, Ana Catarina Sousa, João Luís Viana, Jaime Milheiro, Bruno M. P. M. Oliveira, Franklim Marques, Alejandro Santos and Vitor Hugo Teixeira
Nutrients 2024, 16(11), 1624; https://doi.org/10.3390/nu16111624 (registering DOI) - 26 May 2024
Abstract
In an increasingly aging and overweight population, osteoporosis and type 2 diabetes (T2DM) are major public health concerns. T2DM patients experience prejudicial effects on their bone health, affecting their physical capacity. Exercise in hypoxia (EH) and a low-carbohydrate diet (LCD) have been suggested [...] Read more.
In an increasingly aging and overweight population, osteoporosis and type 2 diabetes (T2DM) are major public health concerns. T2DM patients experience prejudicial effects on their bone health, affecting their physical capacity. Exercise in hypoxia (EH) and a low-carbohydrate diet (LCD) have been suggested for therapeutic benefits in T2DM, improving bone mineral content (BMC) and glycemic control. This study investigated the effects of EH combined with an LCD on body composition and functional and physiologic capacity in T2DM patients. Older T2DM patients (n = 42) were randomly assigned to the following groups: (1) control group: control diet + exercise in normoxia; (2) EH group: control diet + EH; (3) intervention group: LCD + EH. Cardiopulmonary tests (BRUCE protocol), body composition (DEXA), and functional capacity (6MWT, handgrip strength) were evaluated. Body mass index (kg/m2) and body fat (%) decreased in all groups (p < 0.001). BMC (kg) increased in all groups (p < 0.001) and was significantly higher in the EH and EH + LCD groups (p < 0.001). VO2peak improved in all groups (p < 0.001), but more so in the hypoxia groups (p = 0.019). Functional capacity was increased in all groups (p < 0.001), but more so in the EH group in 6MWT (p = 0.030). EH with and without an LCD is a therapeutic strategy for improving bone mass in T2DM, which is associated with cardiorespiratory and functional improvements. Full article
(This article belongs to the Special Issue Diet Quality, Cardiometabolic Risk and Diabetes)
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11 pages, 567 KiB  
Article
The Prevalence and Risk Factors of Low Bone Mineral Density in the Population of the Abay Region of Kazakhstan
by Madina Madiyeva, Tamara Rymbayeva, Alida Kaskabayeva, Gulzhan Bersimbekova, Gulnur Kanapiyanova, Mariya Prilutskaya, Dinara Akhmetzhanova, Aliya Alimbayeva and Nazarbek Omarov
Int. J. Environ. Res. Public Health 2024, 21(6), 681; https://doi.org/10.3390/ijerph21060681 (registering DOI) - 26 May 2024
Abstract
Osteoporosis is considered a serious public health problem that particularly affects the postmenopausal period. In 2018, in the Republic of Kazakhstan, the prevalence of osteoporosis was 10.0, and the incidence was 3.7 new cases, per 100,000 adults, respectively. The objective of this study [...] Read more.
Osteoporosis is considered a serious public health problem that particularly affects the postmenopausal period. In 2018, in the Republic of Kazakhstan, the prevalence of osteoporosis was 10.0, and the incidence was 3.7 new cases, per 100,000 adults, respectively. The objective of this study was to assess the prevalence of osteoporosis and indicate the main factors affecting low bone mineral density by screening the adult population of the Abay region, Kazakhstan. The target group comprised 641 respondents aged between 18 and 65 years old, from a Kazakh population, who had been living in the Abay region since birth. All participants filled out a questionnaire and were subjected to a bone mineral density measurement by means of dual-energy X-ray absorptiometry (DXA) between 15 July 2023 and 29 February 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, such as lifestyle factors and nutritional habits. We identified the prevalence of low bone mass (osteopenia) and osteoporosis to be 34.1%, with the highest prevalence of 48.3% being found in the older population group (50+ years). The regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only four of these showed significance in the final multivariate model (R2 = 22.4%). These were age (adjusted odds ratio (AOR) 1.05) and fracture history (AOR 1.64) directly associated with the likelihood of low bone density. Meanwhile, the body mass index (AOR 0.92) and the consumption of nuts and dried fruits (AOR 0.48) reduced the chance of bone tissue demineralization. Additional studies examining the prevalence and any emerging risk factors for osteoporosis are needed to advance clinical epidemiological knowledge and implement public health programs. Full article
(This article belongs to the Section Global Health)
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22 pages, 4661 KiB  
Article
Microstructure Tailoring for High Strength Ti-6Al-4V without Alloying Elements through Optimized Preheating and Post-Heating Laser Scanning in Laser Powder Bed Fusion
by Ahmet Alptug Tanrikulu, Aditya Ganesh-Ram, Hamidreza Hekmatjou, Sadman Hafiz Durlov, Md Najmus Salehin and Amirhesam Amerinatanzi
Metals 2024, 14(6), 629; https://doi.org/10.3390/met14060629 (registering DOI) - 26 May 2024
Abstract
Ti-6Al-4V with its eclectic array of excellent properties along with the combination of meticulous precision and flexibility offered by the laser powder bed fusion (LPBF) technology makes it a strong proponent in the field of engineering applications. As a substantial amount of research [...] Read more.
Ti-6Al-4V with its eclectic array of excellent properties along with the combination of meticulous precision and flexibility offered by the laser powder bed fusion (LPBF) technology makes it a strong proponent in the field of engineering applications. As a substantial amount of research has paved the way to fabricate Ti-6AL-4V more effectively and efficiently, researchers are becoming more adventurous in finding out the optimal techniques to get better yields in terms of mechanical responses. This includes post-processing techniques i.e., heat treatment (HT) or introducing various alloying elements. Nevertheless, these techniques not only make the overall fabrication more expensive and time-consuming but also contradict the simplistic notion of additive manufacturing (AM) by imparting multistage fabrication without a considerable improvement overall. Here, we propose an innovative breakthrough in the field of Ti-6AL-4V fabrication with LPBF by introducing an in-situ approach to tackle the handicap mentioned in contemporary studies. By imparting multiple laser scans prior to and after the melting scan at each layer, a remarkable 37% improvement in yield strength (YS) can be achieved with higher elongation, while also maintaining a high relative density of around 99.99%. Full article
(This article belongs to the Special Issue Microstructural Tailoring of Metals and Alloys)
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16 pages, 1625 KiB  
Article
Fine-Tuning Artificial Neural Networks to Predict Pest Numbers in Grain Crops: A Case Study in Kazakhstan
by Galiya Anarbekova, Luis Gonzaga Baca Ruiz, Akerke Akanova, Saltanat Sharipova and Nazira Ospanova
Mach. Learn. Knowl. Extr. 2024, 6(2), 1154-1169; https://doi.org/10.3390/make6020054 (registering DOI) - 26 May 2024
Abstract
This study investigates the application of different ML methods for predicting pest outbreaks in Kazakhstan for grain crops. Comprehensive data spanning from 2005 to 2022, including pest population metrics, meteorological data, and geographical parameters, were employed to train the neural network for forecasting [...] Read more.
This study investigates the application of different ML methods for predicting pest outbreaks in Kazakhstan for grain crops. Comprehensive data spanning from 2005 to 2022, including pest population metrics, meteorological data, and geographical parameters, were employed to train the neural network for forecasting the population dynamics of Phyllotreta vittula pests in Kazakhstan. By evaluating various network configurations and hyperparameters, this research considers the application of MLP, MT-ANN, LSTM, transformer, and SVR. The transformer consistently demonstrates superior predictive accuracy in terms of MSE. Additionally, this work highlights the impact of several training hyperparameters such as epochs and batch size on predictive accuracy. Interestingly, the second season exhibits unique responses, stressing the effect of some features on model performance. By advancing our understanding of fine-tuning ANNs for accurate pest prediction in grain crops, this research contributes to the development of more precise and efficient pest control strategies. In addition, the consistent dominance of the transformer model makes it suitable for its implementation in practical applications. Finally, this work contributes to sustainable agricultural practices by promoting targeted interventions and potentially reducing reliance on chemical pesticides. Full article
(This article belongs to the Section Network)
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14 pages, 2410 KiB  
Article
Comparative Evaluation of PCR-Based, LAMP and RPA-CRISPR/Cas12a Assays for the Rapid Detection of Diaporthe aspalathi
by Jiali Dong, Wanzhen Feng, Mingze Lin, Shuzhe Chen, Xiaozhen Liu, Xiaodan Wang and Qinghe Chen
Int. J. Mol. Sci. 2024, 25(11), 5773; https://doi.org/10.3390/ijms25115773 (registering DOI) - 26 May 2024
Abstract
Southern stem canker (SSC) of soybean, attributable to the fungal pathogen Diaporthe aspalathi, results in considerable losses of soybean in the field and has damaged production in several of the main soybean-producing countries worldwide. Early and precise identification of the causal pathogen [...] Read more.
Southern stem canker (SSC) of soybean, attributable to the fungal pathogen Diaporthe aspalathi, results in considerable losses of soybean in the field and has damaged production in several of the main soybean-producing countries worldwide. Early and precise identification of the causal pathogen is imperative for effective disease management. In this study, we performed an RPA-CRISPR/Cas12a, as well as LAMP, PCR and real-time PCR assays to verify and compare their sensitivity, specificity and simplicity and the practicality of the reactions. We screened crRNAs targeting a specific single-copy gene, and optimized the reagent concentrations, incubation temperatures and times for the conventional PCR, real-time PCR, LAMP, RPA and Cas12a cleavage stages for the detection of D. aspalathi. In comparison with the PCR-based assays, two thermostatic detection technologies, LAMP and RPA-CRISPR/Cas12a, led to higher specificity and sensitivity. The sensitivity of the LAMP assay could reach 0.01 ng μL−1 genomic DNA, and was 10 times more sensitive than real-time PCR (0.1 ng μL−1) and 100 times more sensitive than conventional PCR assay (1.0 ng μL−1); the reaction was completed within 1 h. The sensitivity of the RPA-CRISPR/Cas12a assay reached 0.1 ng μL−1 genomic DNA, and was 10 times more sensitive than conventional PCR (1.0 ng μL−1), with a 30 min reaction time. Furthermore, the feasibility of the two thermostatic methods was validated using infected soybean leaf and seeding samples. The rapid, visual one-pot detection assay developed could be operated by non-expert personnel without specialized equipment. This study provides a valuable diagnostic platform for the on-site detection of SSC or for use in resource-limited areas. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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13 pages, 1833 KiB  
Article
Pulmonary Vein Isolation with Pulsed Field Ablation and Size-Adjustable Cryo-Balloon: A Comparative Procedural Analysis of First-Time Use
by Lyuboslav Katov, Yannick Teumer, Carlo Bothner, Wolfgang Rottbauer and Karolina Weinmann-Emhardt
J. Clin. Med. 2024, 13(11), 3113; https://doi.org/10.3390/jcm13113113 (registering DOI) - 26 May 2024
Abstract
Background: Pulmonary vein isolation (PVI) is the standard of care for the treatment of symptomatic atrial fibrillation (AF). Novel techniques for PVI are the thermal size-adjustable cryo-balloon (CB) system and non-thermal pulsed field ablation (PFA) system. There are currently no data available for [...] Read more.
Background: Pulmonary vein isolation (PVI) is the standard of care for the treatment of symptomatic atrial fibrillation (AF). Novel techniques for PVI are the thermal size-adjustable cryo-balloon (CB) system and non-thermal pulsed field ablation (PFA) system. There are currently no data available for a direct comparison between these two systems. Furthermore, with new techniques, it is important to ensure a high level of efficiency and safety during treatment right from initial use. Therefore, the aim of this study was to directly compare the procedural data and safety of these two new PVI techniques in first-time users. Methods: We conducted a single-center prospective study involving 100 consecutive patients with symptomatic atrial fibrillation who underwent first-time PVI using either size-adjustable CB PVI or PFA PVI from July 2023 to March 2024. Results: Acute PVI was achieved in 100% of patients in both groups. First-pass isolation (FPI) was more frequently achieved in the PFA group compared to the size-adjustable CB group. The mean procedural duration and fluoroscopy dose were significantly shorter in the PFA cohort (p < 0.001). Furthermore, a significant reduction in fluoroscopy time was observed during the learning curve within the PFA group (p = 0.023). There were no major complications in both groups. Conclusions: Both systems demonstrate good effectiveness and safety during PVI performed by first-time users. However, the PFA group exhibited a significantly shorter procedural duration. Full article
(This article belongs to the Special Issue Clinical Updates in Cardiac Electrophysiology)
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11 pages, 430 KiB  
Article
Permanent and Persistent Atrial Fibrillations Are Independent Risk Factors of Mortality after Severe COVID-19
by Agnieszka Zając, Ewa Wrona and Jarosław D. Kasprzak
J. Clin. Med. 2024, 13(11), 3112; https://doi.org/10.3390/jcm13113112 (registering DOI) - 26 May 2024
Abstract
Background: The new coronavirus disease (COVID-19), a pandemic infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), had a deep global influence on morbidity and mortality profiles. Comorbidities, especially cardiovascular diseases, were identified to strongly modify the clinical course of COVID-19. However, the [...] Read more.
Background: The new coronavirus disease (COVID-19), a pandemic infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), had a deep global influence on morbidity and mortality profiles. Comorbidities, especially cardiovascular diseases, were identified to strongly modify the clinical course of COVID-19. However, the prognostic role of incident or prevalent atrial fibrillation has not been fully explained. The aim of this study was to evaluate the association between atrial fibrillation and outcomes following hospitalization in patients with severe COVID-19. Methods: We analyzed 199 patients (72 female, median age 70 years) with severe COVID-19 hospitalized between November 2020 and February 2021, due to SARS-CoV-2 infection. The study cohort included 68 patients with a history of AF (34 patients with paroxysmal AF, 19 with permanent AF, 15 patients with persistent AF), and 51 patients presented with AF during hospitalization. Results: Overall mortality during 90 days from the admission to hospital was 41% (n = 82). Non-survivors were older, had significantly elevated inflammation markers (CRP, WBC, procalcitonin, IL-6), NT-proBNP and D-dimer on the first day of hospitalization, lower left ventricular ejection fraction and worse kidney function, as compared to those who stayed alive during the follow-up. Among the hospitalized patients with COVID-19, a history of AF and the presence of AF during hospitalization contributed to higher mortality. Patients with permanent and persistent AF were at the highest risk of death. Different presentations of AF (any history of AF, the subtypes of AF—paroxysmal, permanent, persistent—and the presence of AF during hospitalization) were included in multivariate analysis, aiming to identify independent risk factors of death in the study period. We found that AF was related to worse prognosis, and persistent or permanent forms represented an independent predictor of mortality. Conclusions: Different clinical presentations of AF have varying impacts on survival in severe COVID-19. Mortality in hospitalized patients with severe COVID-19 was higher among patients with a history of AF, especially with persistent and permanent types of AF, and with AF present during hospitalization. Full article
(This article belongs to the Section Cardiology)
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15 pages, 1791 KiB  
Review
Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health
by Fei Qu and Weiwei Zheng
Toxics 2024, 12(6), 388; https://doi.org/10.3390/toxics12060388 (registering DOI) - 26 May 2024
Abstract
Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling [...] Read more.
Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd’s impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. Full article
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30 pages, 11950 KiB  
Article
Till Geochemistry as a Vector to Metasomatic Iron and Alkali-Calcic Systems and Associated Deposits in the Great Bear Magmatic Zone, Northwest Territories, Canada
by Philippe X. Normandeau, Isabelle McMartin and Louise Corriveau
Minerals 2024, 14(6), 547; https://doi.org/10.3390/min14060547 (registering DOI) - 26 May 2024
Abstract
Recent advances in the characterization of metasomatic iron and alkali-calcic (MIAC) systems with associated iron-oxide apatite (IOA) prospects and iron-oxide–copper–gold (IOCG) and metasomatic cobalt deposits of the Great Bear magmatic zone were used to determine if the geochemistry of glacial sediments can unveil [...] Read more.
Recent advances in the characterization of metasomatic iron and alkali-calcic (MIAC) systems with associated iron-oxide apatite (IOA) prospects and iron-oxide–copper–gold (IOCG) and metasomatic cobalt deposits of the Great Bear magmatic zone were used to determine if the geochemistry of glacial sediments can unveil pathfinder elements indicative of mineralization and associated alteration. Analysis of variance within bedrock lithogeochemical (n = 707 samples) and till geochemical datasets (n = 92 samples) are compared. Results show that Fe, Co, Ni, Cu, As, Mo, Bi, La, Th, U, and W were identified as potential vectoring elements in different fractions of till due to their anomalous concentrations down-ice of various mineralized outcrops within the study area. For instance, Fe, Co, Cu, and Mo were established as the most useful vectoring elements in the locally derived till (<2 km down-ice) near the Sue Dianne IOCG deposit, and Fe, Co, Ni, Cu, Mo, W, Bi, and U near the Fab IOCG prospect. At the Sue Dianne deposit, the ratios of near-total (4-acid digestion) versus partial (modified aqua regia digestion) concentrations in the silt + clay-sized till fraction (<0.063 mm) for both La and Th reflect the mineralization alteration signature and define a more consistent dispersal train from mineralization compared to element concentrations mapped alone. Additional testing in an area of continuous till cover near an isolated point source is recommended to further develop the elemental ratio method for exploration of MIAC systems. Full article
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11 pages, 1363 KiB  
Article
A Computational Study of the Mechanism and Kinetics of the 4-Methyl Aniline Reaction with OH Radicals
by Tien V. Pham
Physchem 2024, 4(2), 146-156; https://doi.org/10.3390/physchem4020011 (registering DOI) - 26 May 2024
Abstract
In this study, the mechanism of the reaction between 4-methyl aniline and hydroxyl free radicals was computed using the M06-2X and CCSD(T) methods, along with the 6-311++G(3df,2p) basis set. The kinetics of the reaction were calculated utilizing the transition state theory and the [...] Read more.
In this study, the mechanism of the reaction between 4-methyl aniline and hydroxyl free radicals was computed using the M06-2X and CCSD(T) methods, along with the 6-311++G(3df,2p) basis set. The kinetics of the reaction were calculated utilizing the transition state theory and the microcanonical Rice–Ramsperger–Kassel–Marcus theory. The calculated results revealed that NH-C6H4-CH3 was the key product of the system. The total rate coefficient of the system, k_total = 2.04 × 10−18 T2.07 exp[(11.2 kJ/mol)/RT] cm3/s, was found under the 300–2000 K interval, with P = 760 Torr. At the ambient conditions, the velocity of this reaction was about ten times larger than that of the reaction between C6H5CH3 and hydroxyl free radicals, but it was smaller than the aniline + OH rate. Full article
(This article belongs to the Section Theoretical and Computational Chemistry)
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9 pages, 255 KiB  
Article
Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study
by Maria Dimitriou, Panagiotis Moulos, Ioanna Panagiota Kalafati, Georgia Saranti, Loukianos S. Rallidis and George V. Dedoussis
J. Pers. Med. 2024, 14(6), 565; https://doi.org/10.3390/jpm14060565 (registering DOI) - 26 May 2024
Abstract
Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess [...] Read more.
Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (p-value = 2.63 × 10−25). PGS000012 was associated with a modest increase in CAD risk by 2.2% (p-value = 9.58 × 10−4). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study. Full article
(This article belongs to the Section Omics/Informatics)
12 pages, 1059 KiB  
Review
The Association between Cafestol and Cardiovascular Diseases: A Comprehensive Review
by Wen-Rui Hao, Chun-Yao Cheng, Huan-Yuan Chen, Jin-Jer Chen, Tzu-Hurng Cheng and Ju-Chi Liu
Medicina 2024, 60(6), 867; https://doi.org/10.3390/medicina60060867 (registering DOI) - 26 May 2024
Abstract
Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, [...] Read more.
Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health. Full article
(This article belongs to the Section Cardiology)
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13 pages, 937 KiB  
Review
Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells
by Tadahisa Sugiura, Dhienda C. Shahannaz and Brandon E. Ferrell
Int. J. Mol. Sci. 2024, 25(11), 5772; https://doi.org/10.3390/ijms25115772 (registering DOI) - 26 May 2024
Abstract
Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as [...] Read more.
Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies are employing a range of stem cell varieties. These stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity for unlimited proliferation and differentiation into cardiomyocytes, are a promising cell source for myocardial regeneration therapy. In this review, we discuss the following topics: (1) what are iPSCs; (2) the limitations and solutions for the translation of iPSC-CMs practically; and (3) the current therapeutic clinical trials. Full article
(This article belongs to the Special Issue Exploring Stem Cell Biology for Cardiovascular Regeneration)
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7 pages, 2333 KiB  
Case Report
HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases
by María Carmen Martínez-Romero, María Encarnación Hernández-Contreras, Juan Antonio Bafalliu-Vidal, María Barreda-Sánchez, Teresa Martínez-Menchón, Virginia Cabello-Chaves and Encarna Guillén-Navarro
Genes 2024, 15(6), 687; https://doi.org/10.3390/genes15060687 (registering DOI) - 26 May 2024
Abstract
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, [...] Read more.
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling. Full article
(This article belongs to the Special Issue Genetic Research on Monogenic Skin Disorders)
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13 pages, 3534 KiB  
Article
ATP Hydrolases Superfamily Protein 1 (ASP1) Maintains Root Stem Cell Niche Identity through Regulating Reactive Oxygen Species Signaling in Arabidopsis
by Qianqian Yu, Hongyu Li, Bing Zhang, Yun Song, Yueying Sun and Zhaojun Ding
Plants 2024, 13(11), 1469; https://doi.org/10.3390/plants13111469 (registering DOI) - 26 May 2024
Abstract
The maintenance of the root stem cell niche identity in Arabidopsis relies on the delicate balance of reactive oxygen species (ROS) levels in root tips; however, the intricate molecular mechanisms governing ROS homeostasis within the root stem cell niche remain unclear. In this [...] Read more.
The maintenance of the root stem cell niche identity in Arabidopsis relies on the delicate balance of reactive oxygen species (ROS) levels in root tips; however, the intricate molecular mechanisms governing ROS homeostasis within the root stem cell niche remain unclear. In this study, we unveil the role of ATP hydrolase superfamily protein 1 (ASP1) in orchestrating root stem cell niche maintenance through its interaction with the redox regulator cystathionine β-synthase domain-containing protein 3 (CBSX3). ASP1 is exclusively expressed in the quiescent center (QC) cells and governs the integrity of the root stem cell niche. Loss of ASP1 function leads to enhanced QC cell division and distal stem cell differentiation, attributable to reduced ROS levels and diminished expression of SCARECROW and SHORT ROOT in root tips. Our findings illuminate the pivotal role of ASP1 in regulating ROS signaling to maintain root stem cell niche homeostasis, achieved through direct interaction with CBSX3. Full article
(This article belongs to the Special Issue Plant Root: Anatomy, Structure and Development)
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12 pages, 2042 KiB  
Article
FLT3-TKD Measurable Residual Disease Detection Using Droplet Digital PCR and Clinical Applications in Acute Myeloid Leukemia
by Eric Wenlong Li, Ngoc Yen Kim Tran, Derek McCulloch, Michael Krigstein, Alberto Catalano, Jad Othman, Edward Abadir, Cheryl Smith and Harry Iland
Int. J. Mol. Sci. 2024, 25(11), 5771; https://doi.org/10.3390/ijms25115771 (registering DOI) - 26 May 2024
Abstract
The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This [...] Read more.
The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common FLT3-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with FLT3-TKD variants at diagnosis were tested. Five patients demonstrated clearance of FLT3-TKD clones, but two patients had FLT3-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of FLT3-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration. Full article
(This article belongs to the Special Issue Leukemia: Present and Future)
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13 pages, 1981 KiB  
Article
N-Acetylcysteine Alleviates Impaired Muscular Function Resulting from Sphingosine Phosphate Lyase Functional Deficiency-Induced Sphingoid Base and Ceramide Accumulation in Caenorhabditis elegans
by Min Liu, Yunfei You, Huaiyi Zhu, Yu Chen, Zhenying Hu and Jingjing Duan
Nutrients 2024, 16(11), 1623; https://doi.org/10.3390/nu16111623 (registering DOI) - 26 May 2024
Abstract
Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency [...] Read more.
Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency in Caenorhabditis elegans using spl-1 RNA interference. Within these SPL-deficient nematodes, we observed diminished motility and perturbed muscle fiber organization, correlated with the accumulation of sphingoid bases, their phosphorylated forms, and ceramides (collectively referred to as the “sphingolipid rheostat”). The disturbance in mitochondrial morphology was also notable, as SPL functional loss resulted in heightened levels of reactive oxygen species. Remarkably, the administration of the antioxidant N-acetylcysteine (NAC) ameliorates locomotor impairment and rectifies muscle fiber disarray, underscoring its therapeutic promise for ceramide-accumulation-related muscle disorders. Our findings emphasize the pivotal role of SPL in preserving muscle integrity and advocate for exploring antioxidant interventions, such as NAC supplementation, as prospective therapeutic strategies for addressing muscle function decline associated with sphingolipid/ceramide metabolism disruption. Full article
(This article belongs to the Special Issue Dietary Lipid and Human Health)
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13 pages, 2747 KiB  
Article
Effect of CRISPR/Cas9 Targets Associated with Iron Metabolism and Its Variation on Transcriptional Regulation of SHK-1 Cell Line as a Model for Iron Metabolism
by Phillip Dettleff, Yehwa Jin, Carolina Peñaloza, Rodrigo Pulgar, Alejandro Sáez, Diego Robledo and Sebastian Escobar-Aguirre
Fishes 2024, 9(6), 198; https://doi.org/10.3390/fishes9060198 (registering DOI) - 26 May 2024
Abstract
In this study, we investigated the function of a gene associated with iron metabolism using CRISPR-Cas9 and RNA sequencing in SHK-1 salmon cells. Our objective was to understand how different guide RNA (gRNA) sequences against the transferrin gene tf could influence gene expression [...] Read more.
In this study, we investigated the function of a gene associated with iron metabolism using CRISPR-Cas9 and RNA sequencing in SHK-1 salmon cells. Our objective was to understand how different guide RNA (gRNA) sequences against the transferrin gene tf could influence gene expression and cellular processes related to iron uptake. RNA-Seq analysis was performed to evaluate the transcriptomic effects of two distinct gRNA targets with high knock-out (KO) efficiencies for the targeted tf gene in the SHK-1 genome. Our results showed no significant differential expression in transferrin-related transcripts between wild-type and CRISPR-edited cells; however, there were major differences between their transcriptomes, indicating complex transcriptional regulation changes. Enrichment analysis highlighted specific processes and molecular functions, including those related to the nucleus, cytoplasm, and protein binding. Notably, different sgRNAs targeting tf might result in different mutations at DNA levels in SHK-1 salmon cells. Full article
(This article belongs to the Special Issue Aquatic Animal Transgene and Gene Editing Technology)
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12 pages, 3661 KiB  
Article
An Enhanced Mask R-CNN Approach for Pulmonary Embolism Detection and Segmentation
by Kâmil Doğan, Turab Selçuk and Ahmet Alkan
Diagnostics 2024, 14(11), 1102; https://doi.org/10.3390/diagnostics14111102 (registering DOI) - 26 May 2024
Abstract
Pulmonary embolism (PE) refers to the occlusion of pulmonary arteries by blood clots, posing a mortality risk of approximately 30%. The detection of pulmonary embolism within segmental arteries presents greater challenges compared with larger arteries and is frequently overlooked. In this study, we [...] Read more.
Pulmonary embolism (PE) refers to the occlusion of pulmonary arteries by blood clots, posing a mortality risk of approximately 30%. The detection of pulmonary embolism within segmental arteries presents greater challenges compared with larger arteries and is frequently overlooked. In this study, we developed a computational method to automatically identify pulmonary embolism within segmental arteries using computed tomography (CT) images. The system architecture incorporates an enhanced Mask R-CNN deep neural network trained on PE-containing images. This network accurately localizes pulmonary embolisms in CT images and effectively delineates their boundaries. This study involved creating a local data set and evaluating the model predictions against pulmonary embolisms manually identified by expert radiologists. The sensitivity, specificity, accuracy, Dice coefficient, and Jaccard index values were obtained as 96.2%, 93.4%, 96.%, 0.95, and 0.89, respectively. The enhanced Mask R-CNN model outperformed the traditional Mask R-CNN and U-Net models. This study underscores the influence of Mask R-CNN’s loss function on model performance, providing a basis for the potential improvement of Mask R-CNN models for object detection and segmentation tasks in CT images. Full article
(This article belongs to the Special Issue Classification of Diseases Using Machine Learning Algorithms)
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