The 2023 MDPI Annual Report has
been released!
 
15 pages, 10525 KiB  
Article
Waveform Complexity and Positioning Analysis of Acoustic Emission Events during the Compression Failure Process of a Rock Burst Prone Sample
by Wenlong Zhang, Jiajia Yu, Xiufeng Xu, Jianju Ren, Kaide Liu and Huifang Shi
Buildings 2024, 14(5), 1331; https://doi.org/10.3390/buildings14051331 (registering DOI) - 08 May 2024
Abstract
The localization results of acoustic emission (AE) events can reflect the location and pattern of burst-prone rock failures. However, event localization heavily depends on the quality of the original waveform of the sensor. Therefore, this study analyzed the AE waveform of a rock [...] Read more.
The localization results of acoustic emission (AE) events can reflect the location and pattern of burst-prone rock failures. However, event localization heavily depends on the quality of the original waveform of the sensor. Therefore, this study analyzed the AE waveform of a rock sample under compression to evaluate its failure localization and quality. From the research results, it could be seen that the initial failure was relatively calm, with clear take-off points, which can be better used for accurate AE event positioning. However, the later failure was severe, causing the take-off points of most sensors to be very unclear, and positioning methods that rely on take-off points cannot be used for positioning, let alone simply using the positioning results of the built-in software. This research result reminds researchers who use AE signals for event localization to first examine the quality and status of the original waveform, providing a basis for obtaining accurate localization results, in order to further accurately study the subsequent failure patterns. The above facts indicate that the initial failure is small and scattered, while the later failure is large and concentrated, with certain fractal characteristics. Full article
(This article belongs to the Special Issue Buildings and Infrastructures under Natural Hazards)
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15 pages, 1453 KiB  
Article
Cumin Seed Oil Induces Oxidative Stress-Based Antifungal Activities on Fusarium graminearum
by Emre Yörük, Zeynep Danışman, Murat Pekmez and Tapani Yli-Mattila
Pathogens 2024, 13(5), 395; https://doi.org/10.3390/pathogens13050395 (registering DOI) - 08 May 2024
Abstract
In this study, the antifungal activity of cumin seed oil (CSO) was tested on Fusarium graminearum. (i) Minimum inhibitory concentrations (MICs) and related concentrations (IC75, IC50, and IC25) were detected; (ii) toxicity was evaluated by a [...] Read more.
In this study, the antifungal activity of cumin seed oil (CSO) was tested on Fusarium graminearum. (i) Minimum inhibitory concentrations (MICs) and related concentrations (IC75, IC50, and IC25) were detected; (ii) toxicity was evaluated by a water-soluble tetrazolium salt-1 (WST-1) assay; (iii) genomic/epigenomic alterations were evaluated by the coupled restriction enzyme digestion-random amplification (CRED-RA) method; (iv) oxidative stress was investigated by CAT expression, catalase activity, and DCF-DA staining; (v) deoxynivalenol biosynthesis was evaluated by tri6 expression; (vi) and potential effects of CSO on wheat were tested by a water loss rate (WLR) assay. MIC, IC75, IC50 and IC25 values were detected at 0.5, 0.375, 0.25, and 0.125 mg mL−1. In WST-1 assays, significant decreases (p < 0.001) were detected. Genomic template stability (GTS) related to methylation differences ranged from 94.60% to 96.30%. Percentage polymorphism for HapII/MspI values were as 9.1%/15.8%. CAT (oxidative stress-related catalase) and tri6 (zinc finger motif transcription factor) gene expressions were recorded between 5.29 ± 0.74 and 0.46 ± 0.10 (p < 0.05). Increased catalase activity was detected (p < 0.05) by spectrophotometric assays. DCF-DA-stained (oxidative stressed) cells were increased in response to increased concentrations, and there were no significant changes in WLR values. It was concluded that CSO showed strong antifungal activity on F. graminearum via different physiological levels. Full article
(This article belongs to the Special Issue Current Research on Host–Pathogen Interaction in 2024)
12 pages, 1136 KiB  
Article
Genetic Screening Revealed the Negative Regulation of miR-310~313 Cluster Members on Imd Pathway during Gram-Negative Bacterial Infection in Drosophila
by Yao Li, Yixuan Sun, Ruimin Li, Hongjian Zhou, Shengjie Li and Ping Jin
Genes 2024, 15(5), 601; https://doi.org/10.3390/genes15050601 (registering DOI) - 08 May 2024
Abstract
Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the [...] Read more.
Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the synergistical regulation of miRNAs located within a cluster on the Imd-immune pathway remains obscured. In our study, a genetic screening with 52 transgenic UAS-miRNAs was performed to identify ten miRNAs or miRNA clusters, including the miR310~313 cluster, which may function on Imd-dependent immune responses. The miRNA RT-qPCR analysis showed that the expression of miR-310~313 cluster members exhibited an increase at 6–12 h post E. Coli infection. Furthermore, the overexpression of the miR-310~313 cluster impaired the Drosophila survival. And the overexpression of miR-310/311/312 reduced Dpt expression, an indication of Imd pathway induced by Gram-negative bacteria. Conversely, the knockdown of miR-310/311/312 led to increases in Dpt expression. The Luciferase reporter expression assays and RT-qPCR analysis confirmed that miR-310~313 cluster members directly co-targeted and inhibited Imd transcription. These findings reveal that the members of the miR-310~313 cluster synergistically inhibit Imd-dependent immune responses by co-targeting the Imd gene in Drosophila. Full article
9 pages, 465 KiB  
Article
Role of Lipoprotein Ratios and Remnant Cholesterol in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA)
by Vincenzo Sucato, Luca Di Fazio, Cristina Madaudo, Giuseppe Vadalà, Alessandro D’Agostino, Salvatore Evola, Giuseppina Novo, Egle Corrado and Alfredo Ruggero Galassi
J. Cardiovasc. Dev. Dis. 2024, 11(5), 146; https://doi.org/10.3390/jcdd11050146 (registering DOI) - 08 May 2024
Abstract
Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical situation characterized by evidence of acute myocardial infarction (AMI)—according to the Fourth Universal Definition of Myocardial Infarction—with normal or near-normal coronary arteries on angiographic study (stenosis < 50%). This condition is extremely [...] Read more.
Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical situation characterized by evidence of acute myocardial infarction (AMI)—according to the Fourth Universal Definition of Myocardial Infarction—with normal or near-normal coronary arteries on angiographic study (stenosis < 50%). This condition is extremely variable in etiology, pathogenic mechanisms, clinical manifestations, prognosis and consequently therapeutic approach. Objective: The objective of the study was the evaluation of remnant cholesterol (RC), monocyte/high-density lipoprotein cholesterol ratio (MHR), platelet/lymphocyte ratio (PLR) and various lipoprotein ratios in patients with MINOCA in order to establish their validity as predictors of this event. Materials and Methods: We included 114 patients hospitalized in the Intensive Coronary Care Unit (ICCU) and Hospital Wards of our Hospital Center from 2015 to 2019 who received a diagnosis of MINOCA compared to a control group of 110 patients without previous cardiovascular events. RC was calculated with the following formula: RC = total cholesterol (TC) − HDL-C − LDL-C. MHR was calculated by dividing the monocyte count in peripheral blood by high-density lipoprotein cholesterol (HDL-C) levels; PLR was obtained by dividing platelet count by lymphocyte count. We also calculated various lipoprotein ratios, like total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), and non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol (non-HDL-C/HDL-C) ratios. Results: The MINOCA group had higher mean levels of RC (21.3 ± 10.6 vs. 13.2 ± 7.7 mg/dL), MHR (23 ± 0.009 vs. 18.5± 8.3) and PLR (179.8 ± 246.1 vs. 135 ± 64.7) than the control group. Only the mean values of all calculated lipoprotein ratios were lower in MINOCA patients. Statistical significance was achieved only in the RC evaluation. Conclusions: Higher levels of RC and MHR were found in patients with MINOCA. We also observed higher levels of PLR than in the control group. Only various lipoprotein ratios were lower, but this could reflect the extreme heterogeneity underlying the pathogenic mechanisms of MINOCA. In patients who receive a diagnosis of MINOCA with a baseline alteration of the lipid profile and higher levels of cholesterol at admission as well, the evaluation of these parameters could play an important role, providing more detailed information about their cardiometabolic risk. Full article
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14 pages, 1677 KiB  
Article
Bt-Modified Transgenic Rice May Shift the Composition and Diversity of Rhizosphere Microbiota
by Qixing Huang, Yuliang Zhang, Yanhua Tan, Hua Kong, Yang Cao, Jungang Wang, Guohua Yin and Anping Guo
Plants 2024, 13(10), 1300; https://doi.org/10.3390/plants13101300 (registering DOI) - 08 May 2024
Abstract
Plants significantly shape root-associated microbiota, making rhizosphere microbes useful environmental indicator organisms for safety assessment. Here, we report the pyrosequencing of the bacterial 16S ribosomal RNA in rhizosphere soil samples collected from transgenic cry1Ab/cry1Ac Bt rice Huahui No. 1 (GM crop) and its [...] Read more.
Plants significantly shape root-associated microbiota, making rhizosphere microbes useful environmental indicator organisms for safety assessment. Here, we report the pyrosequencing of the bacterial 16S ribosomal RNA in rhizosphere soil samples collected from transgenic cry1Ab/cry1Ac Bt rice Huahui No. 1 (GM crop) and its parental counterpart, Minghui63. We identified a total of 2579 quantifiable bacterial operational taxonomic units (OTUs). Many treatment-enriched microbial OTUs were identified, including 14 NonGM-enriched OTUs and 10 GM-enriched OTUs. OTUs belonging to the phyla Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes, Nitrospirae, Chlorobi and GN04 were identified as statistically different in abundance between GM and the other two treatments. Compared with the different impacts of different rice varieties on microbiota, the impact of rice planting on microbiota is more obvious. Furthermore, Huahui No. 1 transgenic Bt rice had a greater impact on the rhizosphere bacterial communities than Minghui63. Early developmental stages of the transgenic Bt rice had a significant impact on many Bacillaceae communities. Soil chemical properties were not significantly altered by the presence of transgenic Bt rice. The peak concentration level of Bt protein products was detected during the seedling stage of transgenic Bt rice, which may be an intriguing factor for bacterial diversity variations. Based on these findings, we conclude that transgenic Bt rice has a significant impact on root-associated bacteria. This information may be leveraged in future environmental safety assessments of transgenic Bt rice varieties. Full article
(This article belongs to the Special Issue Detoxification and Control of Mycotoxins in Plants)
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22 pages, 1076 KiB  
Article
Dynamic Changes in Ecosystem Service Value and Ecological Compensation in Original Continuous Poverty-Stricken Areas of China
by Zhe Yu, Chunwei Song and Huishi Du
Sustainability 2024, 16(10), 3947; https://doi.org/10.3390/su16103947 (registering DOI) - 08 May 2024
Abstract
The original contiguous poverty-stricken areas of China (OCPSAC) are a regional complex with natural and human attributes. Their ecosystem services are highly complex in their contribution to human well-being. The region’s ecosystem is unstable and socio-economic development is unbalanced, making it a key [...] Read more.
The original contiguous poverty-stricken areas of China (OCPSAC) are a regional complex with natural and human attributes. Their ecosystem services are highly complex in their contribution to human well-being. The region’s ecosystem is unstable and socio-economic development is unbalanced, making it a key area for research and the implementation of the United Nations Sustainable Development Goals. Therefore, it has become the focus of social attention. This study obtained satellite remote sensing images of the Landsat8 based on the Google Earth Engine. The dynamic characteristics of the spatial and temporal distribution of the OCPSAC’s land use changes in 2015 and 2022 were analyzed. The characteristics of the changes in ecosystem service value (ESV) were quantitatively evaluated through the revised ESV equivalent scale, and the ecological compensation (EC) standards and EC priority level suitable for the region were explored. The research results showed that: (1) the OCPSAC land use types were mainly grassland, forests, and deserts, accounting for more than 80% of the research area; (2) the OCPSAC’s ESV reached CNY 115.578 billion, and the Tibet Region (TR) and Tibetan Region of Four Provinces (TRFP) had the highest ESVs, accounting for 32.28% and 19.64%, respectively. Among individual ESVs, hydrological regulation (HR) and climate regulation (CR) had the highest values, accounting for 55.23% of the research area; (3) the ESV of the research area presented the characteristics of being high in the middle and low at both ends. From the terrain perspective, the areas with a higher ESV per unit area were distributed in the second altitude gradient, followed by China’s third altitude gradient, and the first altitude gradient was the lowest; (4) in the period of 2015–2022, the ESV increased by CNY 21.39 billion, of which TR’s ESV increased by CNY 17.44 billion. From the perspective of a single ESV, the value of waste treatment (WT), HR, nutrient cycle (NC), and provide aesthetic landscape (PAL) increased by CNY 24.38 billion; and (5) in 2022, the EC standard of the OCPSAC was CNY 917.14 billion. High-EC-value areas were mainly distributed in TR and TRFP, accounting for 72.79% of the total compensation amount, of which only TR’s EC amount exceeded a GDP of 2022, accounting for 4.77% of the total compensation. The purpose of this study was to provide a reference for ecosystem sustainability and EC. Full article
11 pages, 567 KiB  
Article
Alexithymia Increases Pericranial and Cervical Muscle Tenderness in Women with Migraine
by Eugenia Rota, Elisa Cavagnetto, Paolo Immovilli, Enrico Frola, Pavel Salari, Nicola Morelli and Alessandro Battaggia
J. Clin. Med. 2024, 13(10), 2772; https://doi.org/10.3390/jcm13102772 (registering DOI) - 08 May 2024
Abstract
Background/Objectives: Alexithymia is characterized by a deficit in identifying and communicating feelings. Emerging evidence suggests that alexithymia is highly prevalent in migraine, in a complex interplay with psychiatric comorbidity. Pericranial/cervical muscle tenderness is a remarkable clinical feature in a large proportion of migraine [...] Read more.
Background/Objectives: Alexithymia is characterized by a deficit in identifying and communicating feelings. Emerging evidence suggests that alexithymia is highly prevalent in migraine, in a complex interplay with psychiatric comorbidity. Pericranial/cervical muscle tenderness is a remarkable clinical feature in a large proportion of migraine patients. This pilot study aimed at investigating the relationship between alexithymia and pericranial/cervical muscle tenderness in female migraineurs. Methods: A total of 42 female patients fulfilling the diagnostic criteria for migraine were enrolled into this pilot, observational, cross-sectional study after informed consent was obtained. Each patient underwent a psychological assessment to identify any alexithymia by means of TAS-20, anxiety/mood comorbidity (by means of STAI-Y1 STAI-Y2, BDI-II), and migraine-related disability (by means of HIT-6), and a physical cranial/cervical musculoskeletal examination. Palpation of pericranial and cervical muscles was carried out in the standardized manner. A Cumulative Muscle Tenderness (CUM) score (0–6) was calculated for each patient. A multivariate analysis was performed to investigate any association amongst the TAS-20 score, the CUM score, and the following covariates: BDI-II, STAI-Y1, STAI-Y2, and HIT-6 scores, age, disease duration, monthly migraine days, and average head pain intensity in the previous three months. Results: Overall, 35.6% of the sample had alexithymia. The multivariate analysis detected a linear and independent relationship between the TAS-20 and CUM scores, with a statistically significant (p = 0.017) association. Conclusions: This pilot study suggests that alexithymia plays a role in increasing pericranial/cervical muscle tenderness in migraine, independently from psychiatric comorbidity. A novel therapeutical approach, targeting alexithymia, may well reduce muscular tenderness in female migraineurs. Full article
(This article belongs to the Special Issue Recent Progress in Multiple Sclerosis and Migraine)
21 pages, 3546 KiB  
Article
Analysis of Grid Performance with Diversified Distributed Resources and Storage Integration: A Bilevel Approach with Network-Oriented PSO
by Ahmad El Sayed and Gokturk Poyrazoglu
Energies 2024, 17(10), 2270; https://doi.org/10.3390/en17102270 (registering DOI) - 08 May 2024
Abstract
The growing deployment of distributed resources significantly affects the distribution grid performance in most countries. The optimal sizing and placement of these resources have become increasingly crucial to mitigating grid issues and reducing costs. Particle Swarm Optimization (PSO) is widely used to address [...] Read more.
The growing deployment of distributed resources significantly affects the distribution grid performance in most countries. The optimal sizing and placement of these resources have become increasingly crucial to mitigating grid issues and reducing costs. Particle Swarm Optimization (PSO) is widely used to address such problems but faces computational inefficiency due to its numerical convergence behavior. This limits its effectiveness, especially for power system problems, because the numerical distance between two nodes in power systems might be different from the actual electrical distance. In this paper, a scalable bilevel optimization problem with two novel algorithms enhances PSO’s computational efficiency. While the resistivity-driven algorithm strategically targets low-resistivity regions and guides PSO toward areas with lower losses, the connectivity-driven algorithm aligns solution spaces with the grid’s physical topology. It prioritizes actual physical neighbors during the search to prevent local optima traps. The tests of the algorithms on the IEEE 33-bus and the 69-bus and Norwegian networks show significant reductions in power losses (up to 74% for PV, wind, and storage) and improved voltage stability (a 21% reduction in mean voltage deviation index) with respect to the results of classical PSO. The proposed network-oriented PSO outperforms classical PSO by achieving a 2.84% reduction in the average fitness value for the IEEE 69-bus case with PV, wind, and storage deployment. The Norwegian case study affirms the effectiveness of the proposed approach in real-world applications through significant improvements in loss reduction and voltage stability. Full article
21 pages, 14688 KiB  
Article
Computational Study on Influence Factors and Vortical Structures in Static Drift Tests
by Chen Yang, Ke Zeng, Jilong Chu, Shuxia Bu and Zhang Zhu
J. Mar. Sci. Eng. 2024, 12(5), 789; https://doi.org/10.3390/jmse12050789 (registering DOI) - 08 May 2024
Abstract
This paper conducted a computational study on the KCS benchmark model at static drift conditions. At the first instance, the roles played by the grid size, turbulence model, and time step are qualitatively and quantitatively analyzed with the orthogonal experimental method (OEM). After [...] Read more.
This paper conducted a computational study on the KCS benchmark model at static drift conditions. At the first instance, the roles played by the grid size, turbulence model, and time step are qualitatively and quantitatively analyzed with the orthogonal experimental method (OEM). After the verification of simulated results compared with experimental data in a Static Oblique Towing Test (OTT), hydrodynamic performance is obtained with the employment of the SST κ-ω turbulence model. The grid size is set as 0.07 m while the time step as 0.01 s. The characteristics of the wake field are illustrated in different forms, such as contours of the free surface, distribution of pressure and hydrodynamic forces, variation of turbulent kinetic energy (TKE), and so on. For a deep insight into the physical mechanisms of the asymmetrical flow field, the Detached Eddy Simulation (DES) method is also utilized to capture vortical structures occurring around the hull, in comparison with results obtained through the Reynolds Averaged Navier Stokes (RANS) model. With the aim of a hydrodynamic derivative estimation or detailed flow characteristics analysis, corresponding selections of the computational method are disparate. Full article
(This article belongs to the Special Issue Application of CFD Simulations to Marine Hydrodynamic Problems)
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15 pages, 1230 KiB  
Article
The Association between Urine N-Glycome and Prognosis after Initial Therapy for Primary Prostate Cancer
by Tijl Vermassen, Nicolaas Lumen, Charles Van Praet, Nico Callewaert, Joris Delanghe and Sylvie Rottey
Biomedicines 2024, 12(5), 1039; https://doi.org/10.3390/biomedicines12051039 (registering DOI) - 08 May 2024
Abstract
Next to prostate-specific antigen, no biochemical biomarkers have been implemented to guide patient follow-up after primary therapy for localized prostate cancer (PCa). We evaluated the prognostic potential of urine N-glycome in terms of event-free survival (EFS) in patients undergoing primary therapy for [...] Read more.
Next to prostate-specific antigen, no biochemical biomarkers have been implemented to guide patient follow-up after primary therapy for localized prostate cancer (PCa). We evaluated the prognostic potential of urine N-glycome in terms of event-free survival (EFS) in patients undergoing primary therapy for PCa. The prognostic features of the urine N-glycosylation profile at diagnosis, assessed in 77 PCa patients, were determined in terms of EFS next to standard clinical parameters. The majority of patients were diagnosed with International Society of Urological Pathology grade ≤ 3 (82%) T1–2 tumors (79%) and without pelvic lymph node invasion (96%). The patients underwent active surveillance (14%), robot-assisted laparoscopic prostatectomy (48%), or external beam radiotherapy (37%). Decreased ratios of biantennary core-fucosylation were noted in patients who developed an event, which was linked to a shorter EFS in both the intention-to-treat cohort and all subcohort analyses. Combining the urine N-glycan biomarker with the D’Amico Risk Classification for PCa resulted in an improved nomogram for patient classification after primary therapy. The rate of urine N-glycan biantennary core-fucosylation, typically linked to more aggressive disease status, is lower in patients who eventually developed an event following primary therapy and subsequently in patients with a worse EFS. The combination of urine N-glycan biomarkers together with clinical parameters could, therefore, improve the post-therapy follow-up of patients with PCa. Full article
(This article belongs to the Special Issue Role of Glycomics in Diagnosis and Prognosis of Cancers)
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22 pages, 11235 KiB  
Article
Urban Morphology Influencing the Urban Heat Island in the High-Density City of Xi’an Based on the Local Climate Zone
by Chongqing Wang, He Zhang, Zhongxu Ma, Huan Yang and Wenxiao Jia
Sustainability 2024, 16(10), 3946; https://doi.org/10.3390/su16103946 (registering DOI) - 08 May 2024
Abstract
Urban form plays a critical role in enhancing urban climate resilience amidst the challenges of escalating global climate change and recurrent high-temperature heatwaves. Therefore, it is crucial to study the correlation between urban spatial form factors and land surface temperature (LST). This study [...] Read more.
Urban form plays a critical role in enhancing urban climate resilience amidst the challenges of escalating global climate change and recurrent high-temperature heatwaves. Therefore, it is crucial to study the correlation between urban spatial form factors and land surface temperature (LST). This study utilized Landsat 8 remote sensing data to estimate LST. Random forest nonlinear analysis was employed to investigate the interaction between the urban heat island (UHI) and six urban morphological factors: building density (BD), floor area ratio (FAR), building height (BH), fractional vegetation coverage (FVC), sky view factor (SVF), and impervious surface fraction (ISF), within the framework of local climate zones (LCZs). Key findings revealed that Xi’an exhibited a significant urban heat island effect, with over 10% of the study area experiencing temperatures exceeding 40 °C. Notably, the average LST of building-class LCZs (1-6) was 3.5 °C higher than that of land cover-class LCZs (A-C). Specifically, compact LCZs (1-3) had an average LST 3.02 °C higher than open LCZs (4-6). FVC contributed the most to the variation in LST, while FAR contributed the least. ISF and BD were found to have a positive impact on LST, while FVC and BH had a negative influence. Moreover, SVF was observed to positively influence LST in the compact classes (LCZ2-3) and open low-rise class (LCZ6). In the open mid-rise class (LCZ5), SVF and LST showed a U-shaped relationship. There is an inverted U-shaped relationship between FAR and LST, with the inflection point occurring at 1.5. The results of nonlinear analysis were beneficial in illustrating the complex relationships between LST and its driving factors. The study’s results highlight the effectiveness of utilizing LCZ as a detailed approach to explore the relationship between urban morphology and urban heat islands. Recommendations for enhancing urban climate resilience include strategies such as increasing vegetation coverage, regulating building heights, organizing buildings in compact LCZs in an “L” or “I” shape, and adopting an “O” or “C” configuration for buildings in open LCZs to aid planners in developing sustainable urban environments. Full article
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7 pages, 3022 KiB  
Case Report
New Case of Spinocerebellar Ataxia, Autosomal Recessive 4, Due to VPS13D Variants
by Denis Kistol, Polina Tsygankova, Fatima Bostanova, Maria Orlova and Ekaterina Zakharova
Int. J. Mol. Sci. 2024, 25(10), 5127; https://doi.org/10.3390/ijms25105127 (registering DOI) - 08 May 2024
Abstract
Movement disorders such as bradykinesia, tremor, dystonia, chorea, and myoclonus most often arise in several neurodegenerative diseases with basal ganglia and white matter involvement. While the pathophysiology of these disorders remains incompletely understood, dysfunction of the basal ganglia and related brain regions is [...] Read more.
Movement disorders such as bradykinesia, tremor, dystonia, chorea, and myoclonus most often arise in several neurodegenerative diseases with basal ganglia and white matter involvement. While the pathophysiology of these disorders remains incompletely understood, dysfunction of the basal ganglia and related brain regions is often implicated. The VPS13D gene, part of the VPS13 family, has emerged as a crucial player in neurological pathology, implicated in diverse phenotypes ranging from movement disorders to Leigh syndrome. We present a clinical case of VPS13D-associated disease with two variants in the VPS13D gene in an adult female. This case contributes to our evolving understanding of VPS13D-related diseases and underscores the importance of genetic screening in diagnosing and managing such conditions. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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19 pages, 867 KiB  
Article
Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort (“PEMBROREAL” Study)
by Alessandro Cafaro, Flavia Foca, Oriana Nanni, Marco Chiumente, Marina Coppola, Alberto Russi, Elena Svegliati, Paolo Baldo, Sabrina Orzetti, Fiorenza Enrico, Federico Foglio, Davide Pinnavaia, Vito Ladisa, Claudia Lauria Pantano, Rosa Lerose, Patrizia Nardulli, Simona Ferraiuolo, Piera Maiolino, Immacolata De Stasio, Federica Gradellini, Anna Rita Gasbarro, Rossella Santeramo, Gisella Carrucciu, Riccardo Provasi, Mario Cirino, Paola Cristina Cappelletto, Elisabetta Fonzi, Alessandra Pasqualini, Stefano Vecchia, Marianna Veraldi, Adele Emanuela De Francesco, Lucio Crinò, Angelo Delmonte and Carla Masiniadd Show full author list remove Hide full author list
Cancers 2024, 16(10), 1802; https://doi.org/10.3390/cancers16101802 (registering DOI) - 08 May 2024
Abstract
Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine [...] Read more.
Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan–Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6–10.0) and 25.5 months (95% CI: 21.8–31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution. Full article
17 pages, 653 KiB  
Review
Spinal Cord Injury Management Based on Microglia-Targeting Therapies
by Thomas Gabriel Schreiner, Oliver Daniel Schreiner and Romeo Cristian Ciobanu
J. Clin. Med. 2024, 13(10), 2773; https://doi.org/10.3390/jcm13102773 (registering DOI) - 08 May 2024
Abstract
Spinal cord injury is a complicated medical condition both from the clinician’s point of view in terms of management and from the patient’s perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate [...] Read more.
Spinal cord injury is a complicated medical condition both from the clinician’s point of view in terms of management and from the patient’s perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate use of modern imaging techniques and convenient surgical spinal cord decompression and stabilization. In this context, there is a mandatory need for novel adjunctive therapeutic approaches to classical treatments to improve rehabilitation chances and clinical outcomes. This review offers a new and original perspective on therapies targeting the microglia, one of the most relevant immune cells implicated in spinal cord disorders. The first part of the manuscript reviews the anatomical and pathophysiological importance of the blood-spinal cord barrier components, including the role of microglia in post-acute neuroinflammation. Subsequently, the authors present the emerging therapies based on microglia modulation, such as cytokines modulators, stem cell, microRNA, and nanoparticle-based treatments that could positively impact spinal cord injury management. Finally, future perspectives and challenges are also highlighted based on the ongoing clinical trials related to medications targeting microglia. Full article
(This article belongs to the Special Issue Clinical Management and Rehabilitation of Spinal Cord Injury)
14 pages, 634 KiB  
Article
Screening and In Silico Analyses of the Yeast Saccharomyces cerevisiae Σ1278b Bank Mutants Using Citral as a Natural Antimicrobial
by Rolla El Harati, Francesco Fancello, Chiara Multineddu, Giacomo Zara and Severino Zara
Foods 2024, 13(10), 1457; https://doi.org/10.3390/foods13101457 (registering DOI) - 08 May 2024
Abstract
The antimicrobial function of citral, one of the main compounds of the essential oils (EO) of the Citrus genus, and widely used by the food industry toward spoilage yeast, was previously proven. In this study, the possible mode of action of citral against [...] Read more.
The antimicrobial function of citral, one of the main compounds of the essential oils (EO) of the Citrus genus, and widely used by the food industry toward spoilage yeast, was previously proven. In this study, the possible mode of action of citral against yeast cells was evaluated by using a global deletome approach. Firstly, the suitability of Saccharomyces cerevisiae Σ1278b to serve as model yeast was assessed by determining its sensitivity to citral (MIC = 0.5 μL/mL). Subsequently, the complete library of Σ1278b haploid mutants deleted in 4019 non-essential genes was screened to identify potential molecular targets of citral. Finally, the deleted genes in the 590 mutants showing increased citral resistance was analyzed with an in-silico approach (Gene Ontology). The significantly enriched GO Terms were “cytoplasm”, “vacuole”, and “mitochondrion” (cellular components); “catalytic activity” (molecular function); “pseudohyphal growth” (biological process). For molecular function, resistant mutants were grouped into thiosulfate sulfur transferase activity, transferase activity, and oxidoreductase activity; for cellular components, resistant mutants were grouped as: cytoplasm, intracellular organelle, membrane-bounded organelle, mitochondrion, organelle membrane, and vacuole; and finally, with regard to biological process, deleted genes were grouped as: pseudohyphal growth, mitochondrion organization, lipid metabolic process, DNA recombination and repair, and proteolysis. Interestingly, many identified genes were associated with the cellular response to oxidative stress and ROS scavenging. These findings have important implications for the development of citral-based antimicrobials and the elucidation of its mechanism of action. Full article
(This article belongs to the Section Food Microbiology)
27 pages, 3347 KiB  
Article
Quadratic American Strangle Options in Light of Two-Sided Optimal Stopping Problems
by Tsvetelin Stefanov Zaevski
Mathematics 2024, 12(10), 1449; https://doi.org/10.3390/math12101449 (registering DOI) - 08 May 2024
Abstract
The aim of this paper is to examine some American-style financial instruments that lead to two-sided optimal hitting problems. We pay particular attention to derivatives that are similar to strangle options but have a quadratic payoff function. We consider these derivatives in light [...] Read more.
The aim of this paper is to examine some American-style financial instruments that lead to two-sided optimal hitting problems. We pay particular attention to derivatives that are similar to strangle options but have a quadratic payoff function. We consider these derivatives in light of much more general payoff structures under certain conditions which guarantee that the optimal strategy is an exit from a strip. Closed-form formulas for the optimal boundaries and the fair price are derived when the contract has no maturity constraints. We obtain the form of the optimal boundaries under the finite maturity horizon and approximate them by maximizing the financial utility of the derivative holder. The Crank–Nicolson finite difference method is applied to the pricing problem. The importance of these novel financial instruments is supported by several features that are very useful for financial practice. They combine the characteristics of the power options and the ordinary American straddles. Quadratic strangles are suitable for investors who need to hedge strongly, far from the strike positions. In contrast, the near-the-money positions offer a relatively lower payoff than the ordinary straddles. Note that the usual options pay exactly the overprice; no more, no less. In addition, the quadratic strangles allow investors to hedge the positions below and above the strike together. This is very useful in periods of high volatility when large market movements are expected but their direction is unknown. Full article
(This article belongs to the Section Financial Mathematics)
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16 pages, 1137 KiB  
Article
Dynamic Height Growth Equations and Site Index-Based Biomass Models for Young Native Species Afforestations in Spain
by Rafael Calama, Guillermo Madrigal, Miren del Río, Eduardo López-Senespleda, Marta Pardos, Ricardo Ruiz-Peinado and María Menéndez-Miguélez
Forests 2024, 15(5), 827; https://doi.org/10.3390/f15050827 (registering DOI) - 08 May 2024
Abstract
The expansion of forested areas through afforestation and reforestation is widely recognized as a highly effective natural solution for mitigating climate change. Accurately assessing the potential carbon uptake capacity of newly afforested areas requires modelling tools to estimate biomass stocks, including site index [...] Read more.
The expansion of forested areas through afforestation and reforestation is widely recognized as a highly effective natural solution for mitigating climate change. Accurately assessing the potential carbon uptake capacity of newly afforested areas requires modelling tools to estimate biomass stocks, including site index curves and biomass models. Given the unique conditions in terms of tree size, uniform spacing, and tree allometries observed in young afforestations compared to natural stands, specific tools are necessary. In Spain, over 800,000 ha has been afforested with native forest species since 1992, but specific modelling tools for these plantations are lacking. Using data from 370 stem analyses collected across an extensive network of plots in young afforestations, we developed dynamic height growth and site index models for the main native species (five pines and five oaks) commonly used in afforestation in Spain. We compared various nonlinear models, such as ADA (algebraic difference approach) and GADA (generalized algebraic difference approach) expansions. The developed site index models were then used to predict the total biomass stored in the afforestation. Our results underscore the necessity for specific site index models tailored to afforestations, as well as the potential of the established site index in predicting biomass and carbon fixation capacity in these young forests. Full article
(This article belongs to the Special Issue Forest Growth Modeling in Different Ecological Conditions)
25 pages, 4460 KiB  
Article
Multi-Scale Fusion Siamese Network Based on Three-Branch Attention Mechanism for High-Resolution Remote Sensing Image Change Detection
by Yan Li, Liguo Weng, Min Xia, Kai Hu and Haifeng Lin
Remote Sens. 2024, 16(10), 1665; https://doi.org/10.3390/rs16101665 (registering DOI) - 08 May 2024
Abstract
Remote sensing image change detection (CD) is an important means in remote sensing data analysis tasks, which can help us understand the surface changes in high-resolution (HR) remote sensing images. Traditional pixel-based and object-based methods are only suitable for low- and medium-resolution images, [...] Read more.
Remote sensing image change detection (CD) is an important means in remote sensing data analysis tasks, which can help us understand the surface changes in high-resolution (HR) remote sensing images. Traditional pixel-based and object-based methods are only suitable for low- and medium-resolution images, and are still challenging for complex texture features and detailed image detail processing in HR images. At present, the method based on deep learning has problems such as inconsistent fusion and difficult model training in the combination of the difference feature information of the deep and shallow layers and the attention mechanism, which leads to errors in the distinction between the changing region and the invariant region, edge detection and small target detection. In order to solve the above problems of inconsistent fusions of feature information aggregation and attention mechanisms, and indistinguishable change areas, we propose a multi-scale feature fusion Siamese network based on attention mechanism (ABMFNet). To tackle the issues of inconsistent fusion and alignment difficulties when integrating multi-scale fusion and attention mechanisms, we introduce the attention-based multi-scale feature fusion module (AMFFM). This module not only addresses insufficient feature fusion and connection between different-scale feature layers, but also enables the model to automatically learn and prioritize important features or regions in the image. Additionally, we design the cross-scale fusion module (CFM) and the difference feature enhancement pyramid structure (DEFPN) to assist the AMFFM module in integrating differential information effectively. These modules bridge the spatial disparity between low-level and high-level features, ensuring efficient connection and fusion of spatial difference information. Furthermore, we enhance the representation and inference speed of the feature pyramid by incorporating a feature enhancement module (FEM) into DEFPN. Finally, the BICD dataset proposed by the laboratory and public datasets LEVIR-CD and BCDD are compared and tested. We use F1 score and MIoU values as evaluation metrics. For AMBMFNet, the F1 scores on the three datasets are 77.69%, 81.57%, and 77.91%, respectively, while the MIoU values are 84.65%, 85.84%, and 84.54%, respectively. The experimental results show that ABMFNet has better effectiveness and robustness. Full article
(This article belongs to the Section Environmental Remote Sensing)
17 pages, 2466 KiB  
Article
A Novel Approach Using Reduced Graphene Oxide for the Detection of ALP and RUNX2 Osteogenic Biomarkers
by Elena Alina Chiticaru and Mariana Ioniță
Curr. Issues Mol. Biol. 2024, 46(5), 4489-4505; https://doi.org/10.3390/cimb46050272 (registering DOI) - 08 May 2024
Abstract
In this work, we propose a new technique involving the modification of commercial screen-printed carbon electrodes with electrochemically reduced graphene oxide to serve as the starting point of a future electrochemical biosensor for the detection of two osteogenic biomarkers: alkaline phosphatase (ALP) and [...] Read more.
In this work, we propose a new technique involving the modification of commercial screen-printed carbon electrodes with electrochemically reduced graphene oxide to serve as the starting point of a future electrochemical biosensor for the detection of two osteogenic biomarkers: alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2). The electrodes were characterized after each modification by cyclic voltammetry and electrochemical impedance spectroscopy, showing the appropriate electrochemical characteristics for each modification type. The results obtained from scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and contact angle measurements are well correlated with each other, demonstrating the successful modification of the electrodes with graphene oxide and its subsequent reduction. The bioreceptors were immobilized on the electrodes by physical adsorption, which was confirmed by electrochemical methods, structural characterization, and contact angle measurements. Finally, the functionalized electrodes were incubated with the specific target analytes and the detection relied on monitoring the electrochemical changes occurring after the hybridization process. Our results indicated that the pilot platform has the ability to detect the two biomarkers up to 1 nM, with increased sensitivity observed for RUNX2, suggesting that after further optimizations, it has a high potential to be employed as a future biosensor. Full article
(This article belongs to the Special Issue Molecular Imaging of Cells and Tissues)
18 pages, 9608 KiB  
Article
Prediction of Drug-Target Affinity Using Attention Neural Network
by Xin Tang, Xiujuan Lei and Yuchen Zhang
Int. J. Mol. Sci. 2024, 25(10), 5126; https://doi.org/10.3390/ijms25105126 (registering DOI) - 08 May 2024
Abstract
Studying drug-target interactions (DTIs) is the foundational and crucial phase in drug discovery. Biochemical experiments, while being the most reliable method for determining drug-target affinity (DTA), are time-consuming and costly, making it challenging to meet the current demands for swift and efficient drug [...] Read more.
Studying drug-target interactions (DTIs) is the foundational and crucial phase in drug discovery. Biochemical experiments, while being the most reliable method for determining drug-target affinity (DTA), are time-consuming and costly, making it challenging to meet the current demands for swift and efficient drug development. Consequently, computational DTA prediction methods have emerged as indispensable tools for this research. In this article, we propose a novel deep learning algorithm named GRA-DTA, for DTA prediction. Specifically, we introduce Bidirectional Gated Recurrent Unit (BiGRU) combined with a soft attention mechanism to learn target representations. We employ Graph Sample and Aggregate (GraphSAGE) to learn drug representation, especially to distinguish the different features of drug and target representations and their dimensional contributions. We merge drug and target representations by an attention neural network (ANN) to learn drug-target pair representations, which are fed into fully connected layers to yield predictive DTA. The experimental results showed that GRA-DTA achieved mean squared error of 0.142 and 0.225 and concordance index reached 0.897 and 0.890 on the benchmark datasets KIBA and Davis, respectively, surpassing the most state-of-the-art DTA prediction algorithms. Full article
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16 pages, 3382 KiB  
Article
Neural Network-Based Detection of OCC Signals in Lighting-Constrained Environments: A Museum Use Case
by Saray Rufo, Lidia Aguiar-Castillo, Julio Rufo and Rafael Perez-Jimenez
Electronics 2024, 13(10), 1828; https://doi.org/10.3390/electronics13101828 (registering DOI) - 08 May 2024
Abstract
This research presents a novel approach by applying convolutional neural networks (CNNs) to enhance optical camera communication (OCC) signal detection under challenging indoor lighting conditions. The study utilizes a smartphone app to capture images of an LED lamp that emits 25 unique optical [...] Read more.
This research presents a novel approach by applying convolutional neural networks (CNNs) to enhance optical camera communication (OCC) signal detection under challenging indoor lighting conditions. The study utilizes a smartphone app to capture images of an LED lamp that emits 25 unique optical codes at distances of up to four meters. The developed CNN model demonstrates superior accuracy and outperforms traditional methodologies, which often struggle under variable illumination. This advancement provides a robust solution for reliable OCC detection where previous methods underperform, particularly in the tourism industry, where it can be used to create a virtual museum on the Unity platform. This innovation showcases the potential of integrating the application with a virtual environment to enhance tourist experiences. It also establishes a comprehensive visible light positioning (VLP) system, marking a significant advance in using CNN for OCC technology in various lighting conditions. The findings underscore the effectiveness of CNNs in overcoming ambient lighting challenges, paving the way for new applications in museums and similar environments and laying the foundation for future OCC system improvements. Full article
(This article belongs to the Special Issue Next-Generation Indoor Wireless Communication)
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16 pages, 1612 KiB  
Article
The Expression and Epigenetic Characteristics of the HSF2 Gene in Cattle-Yak and the Correlation with Its Male Sterility
by Qinhui Yang, Yumian Xie, Bangting Pan, Yuying Cheng, Yanjin Zhu, Xixi Fei, Xupeng Li, Jun Yu, Zhuo Chen, Jian Li and Xianrong Xiong
Animals 2024, 14(10), 1410; https://doi.org/10.3390/ani14101410 (registering DOI) - 08 May 2024
Abstract
Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription factor that is involved in the regulation of diverse developmental pathways. However, the role and the corresponding [...] Read more.
Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription factor that is involved in the regulation of diverse developmental pathways. However, the role and the corresponding molecular mechanism of HSF2 in male cattle-yak sterility are still poorly understood. Therefore, the aim of this study was to obtain the sequence and the biological information of the cattle-yak HSF2 gene and to investigate the spatiotemporal expression profiles of the locus during the development of cattle-yak testes. Additionally, the differential expression was analyzed between the cattle-yak and the yak, and the methylation of corresponding promoter regions was compared. Our results showed an additional 54 bp fragment and a missense mutation (lysine to glutamic acid) were presented in the cattle-yak HSF2 gene, which correlated with enriched expression in testicular tissue. In addition, the expression of the HSF2 gene showed dynamic changes during the growth of the testes, reaching a peak in adulthood. The IHC indicated that HSF2 protein was primarily located in spermatocytes (PS), spermatogonia (SP), and Sertoli cells (SC) in cattle-yak testes, compared with the corresponding cells of cattle and the yak. Furthermore, bisulfite-sequencing PCR (BSP) revealed that the methylated CpG sites in the promoter region of the cattle-yak HSF2 were more numerous than in the yak counterpart, which suggests hypermethylation of this region in the cattle-yak. Taken together, the low expression abundance and hypermethylation of HSF2 may underpin the obstruction of spermatogenesis, which leads to male cattle-yak infertility. Our study provided a basic guideline for the HSF2 gene in male reproduction and a new insight into the mechanisms of male cattle-yak sterility. Full article
(This article belongs to the Section Animal Reproduction)
24 pages, 670 KiB  
Article
Do Natural Disasters Reduce Loans to the More CO2-Emitting Sectors?
by Antonio Forte, Selay Sahan and Damiano B. Silipo
Sustainability 2024, 16(10), 3943; https://doi.org/10.3390/su16103943 (registering DOI) - 08 May 2024
Abstract
We studied the impact of major floods occurring in Turkey between 2005 and 2020 on lending and the allocation of loans between sectors that differ in their CO2 emissions. Our evidence shows that the floods are not significant determinants of lending or [...] Read more.
We studied the impact of major floods occurring in Turkey between 2005 and 2020 on lending and the allocation of loans between sectors that differ in their CO2 emissions. Our evidence shows that the floods are not significant determinants of lending or the allocation of loans between sectors, even though CO2 emissions contribute to the reallocation of loans from the more polluting to the less polluting sectors. Indeed, risks and returns of the sector remain the main determinants of lending and of the allocation of loans among sectors. The results are robust to alternative estimation methods and specifications of the econometric models. Since in the period of investigation no environmental regulations were implemented in Turkey, and the Paris Agreement was ratified only at end-2021, the evidence suggests that more stringent regulations and green policies are required to accelerate the green transition in Turkey. Full article

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