The 2023 MDPI Annual Report has
been released!
 
26 pages, 2600 KiB  
Review
Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases
by Juanjuan Han, Cuijing Wang, Haolin Yang, Jiayi Luo, Xiaoyi Zhang and Xin-An Zhang
Biomolecules 2024, 14(5), 514; https://doi.org/10.3390/biom14050514 (registering DOI) - 24 Apr 2024
Abstract
Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become [...] Read more.
Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1–0.4% adenylate residues, especially at the beginning of 3′-UTR near the translation stop codon. The m6A regulator can be classified into three types, namely the “writer”, “reader”, and “eraser”. Studies have shown that the epigenetic modulation of m6A influences mRNA processing, nuclear export, translation, and splicing. Regulated cell death (RCD) is the autonomous and orderly death of cells under genetic control to maintain the stability of the internal environment. Moreover, distorted RCDs are widely used to influence the course of various diseases and receiving increasing attention from researchers. In the past few years, increasing evidence has indicated that m6A can regulate gene expression and thus influence different RCD processes, which has a central role in the etiology and evolution of MSDs. The RCDs currently confirmed to be associated with m6A are autophagy-dependent cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic cell death, NETotic cell death and oxeiptosis. The m6A–RCD axis can regulate the inflammatory response in chondrocytes and the invasive and migratory of MM cells to bone remodeling capacity, thereby influencing the development of MSDs. This review gives a complete overview of the regulatory functions on the m6A–RCD axis across muscle, bone, and cartilage. In addition, we also discuss recent advances in the control of RCD by m6A-targeted factors and explore the clinical application prospects of therapies targeting the m6A–RCD in MSD prevention and treatment. These may provide new ideas and directions for understanding the pathophysiological mechanism of MSDs and the clinical prevention and treatment of these diseases. Full article
24 pages, 1611 KiB  
Article
The Effectiveness of Climate Adaptation Finance and Readiness on Vulnerability in African Economies
by Purity Maina and Anett Parádi-Dolgos
Climate 2024, 12(5), 59; https://doi.org/10.3390/cli12050059 (registering DOI) - 24 Apr 2024
Abstract
Addressing climate vulnerability remains a priority for economies globally. This study used the panel-corrected standard error (PCSE) methodology to investigate the impact of adaptation financing on climate vulnerability. This analysis examined 52 African countries from 2012 to 2021 while considering their climate adaptation [...] Read more.
Addressing climate vulnerability remains a priority for economies globally. This study used the panel-corrected standard error (PCSE) methodology to investigate the impact of adaptation financing on climate vulnerability. This analysis examined 52 African countries from 2012 to 2021 while considering their climate adaptation readiness. The impact was also assessed based on the Human Development Index (HDI) categories to reflect different levels of development. The findings showed that adaptation finance considerably influenced climate vulnerability reduction in Africa, particularly in nations with a moderate HDI. However, most countries still need higher levels of adaptation financing, resulting in a small impact on vulnerability reduction. Furthermore, the impact of readiness measures differed by HDI category. Economic and social climate readiness strongly impacted climate vulnerability in high-HDI nations, but governance preparedness was more critical in low-HDI countries. Based on the empirical facts, two policy proposals emerge. First, it is critical to reconsider the distribution of adaptation financing to reduce disparities and effectively alleviate climate vulnerability. Moreover, African economies should consider implementing innovative localized financing mechanisms to mobilize extra adaptation finance. Second, African governments should customize climate readiness interventions based on their HDI levels to improve the achievement of a positive impact on climate vulnerability. Full article
17 pages, 1373 KiB  
Article
Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer—A Model Study on Azoxymethane-Treated Rats
by Jacek Wilczak, Adam Prostek, Katarzyna Dziendzikowska, Małgorzata Gajewska, Łukasz Kopiasz, Joanna Harasym, Michał Oczkowski and Joanna Gromadzka-Ostrowska
Int. J. Mol. Sci. 2024, 25(9), 4635; https://doi.org/10.3390/ijms25094635 (registering DOI) - 24 Apr 2024
Abstract
Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of [...] Read more.
Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)
11 pages, 1098 KiB  
Article
Cadaveric Study on Comparison of Neck Extension Angles for Endotracheal Intubation in Rabbits Using a Rigid and Flexible Endoscope
by Nicharee Luevitoonvechakij, Nithidol Buranapim, Witaya Suriyasathaporn, Pakkanut Bansiddhi, Kanawee Warrit, Veerasak Punyapornwithaya and Wanna Suriyasathaporn
Animals 2024, 14(9), 1270; https://doi.org/10.3390/ani14091270 (registering DOI) - 24 Apr 2024
Abstract
Endotracheal intubation in rabbits is always challenging due to the unique anatomical conformation. To improve endotracheal intubation success, this study determined the relationship between head placement angles guided by endoscope-assisted visualization techniques and the endotracheal intubation success rate. Thirty-two rabbit cadavers were used [...] Read more.
Endotracheal intubation in rabbits is always challenging due to the unique anatomical conformation. To improve endotracheal intubation success, this study determined the relationship between head placement angles guided by endoscope-assisted visualization techniques and the endotracheal intubation success rate. Thirty-two rabbit cadavers were used in the study. Six veterinary practitioners who had no experience with rabbit endotracheal intubation were randomly assigned to intubate rabbit cadavers using the guidance of either a rigid endoscope (RE) or flexible endoscope (FE), with the head placement angles with an ascending neck at 90, 100, 110, 120 and 130 degrees. The endotracheal intubation completed in 90 s was determined to be a success. The success rates using RE and FE were 97.2% and 95.9%, respectively. The means and standard error of means (SEM) of endotracheal intubation times guided by RE and FE were 53.7 ± 4.68 and 55.2 ± 4.24 s, respectively. Results from survival time analysis show that the five veterinarians successfully intubated the rabbit within 90 s, regardless of the different types of endoscopes. Angle was the only significant factor that affected the endotracheal intubation success. The head placement angle at 110 and 120 degrees had the highest success rate of endotracheal intubation compared to 90 degrees (p ≤ 0.05). In conclusion, for inexperienced veterinarians, the success of endotracheal intubation in rabbits, guided by endoscope-assisted visualized techniques regardless of rigid endoscope or flexible endoscope guidance, is improved when the head extension is 110 and 120 degrees. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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11 pages, 5339 KiB  
Article
Exploring Skin Interactions with 5G Millimeter-Wave through Fluorescence Lifetime Imaging Microscopy
by Negin Foroughimehr, Andrew H. A. Clayton and Ali Yavari
Electronics 2024, 13(9), 1630; https://doi.org/10.3390/electronics13091630 (registering DOI) - 24 Apr 2024
Abstract
The ongoing expansion of fifth-generation (5G) and future sixth-generation (6G) mobile communications is expected to result in widespread human exposure to millimeter-wave (mmWave) radiation globally. Given the short penetration depth of mmWaves and their high absorption by the skin, it is imperative to [...] Read more.
The ongoing expansion of fifth-generation (5G) and future sixth-generation (6G) mobile communications is expected to result in widespread human exposure to millimeter-wave (mmWave) radiation globally. Given the short penetration depth of mmWaves and their high absorption by the skin, it is imperative to investigate the potential effects of 5G radiation not only in terms of temperature increase but also at the cellular level. To understand the biological mechanisms of mmWave effects, accurate methods for assessing mmWave absorption in the skin are crucial. In this study, we use fluorescence lifetime imaging microscopy (FLIM) to explore these effects. Employing a mmWave exposure system operating at 26 gigahertz (GHz), porcine skin is irradiated for varying durations (5, 10, 20, and 30 min). We investigate changes in tissue temperature and the autofluorescence of flavin adenine dinucleotide (FAD). Our findings suggest that operating our mmWave exposure systems at the configured power level of 26 GHz is unlikely to cause damage to FADs, even after a 30 min exposure duration. Full article
(This article belongs to the Section Microwave and Wireless Communications)
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24 pages, 2843 KiB  
Article
Numerical Study on the Swimming and Energy Self-Sufficiency of Multi-Joint Robotic Fish
by Guodu Liang, Zhiqiang Xin, Quanlin Ding, Songyang Liu and Liying Ren
J. Mar. Sci. Eng. 2024, 12(5), 701; https://doi.org/10.3390/jmse12050701 (registering DOI) - 24 Apr 2024
Abstract
Energy is one of the primary challenges in the long-term operation of robotic fish. The research on combining wave energy-harvesting technology with robotic fish for energy supplementation is not extensive, and there is insufficient comprehensive analysis on energy harvesting from waves and energy [...] Read more.
Energy is one of the primary challenges in the long-term operation of robotic fish. The research on combining wave energy-harvesting technology with robotic fish for energy supplementation is not extensive, and there is insufficient comprehensive analysis on energy harvesting from waves and energy costs during swimming. Therefore, the energy self-sufficiency of multi-joint robotic fish is investigated by employing the coupling method of smoothed particle hydrodynamics (SPH) and multi-body dynamics in this study. A reversible energy conversion mechanism is applied to the robotic fish, serving as a driving system during swimming and as a power take-off (PTO) system during energy harvesting. The energy costs of the multi-joint robotic fish under various undulation parameters (including amplitude, frequency, and body wavelength) are analyzed, along with an examination of the influence of the PTO system on energy harvesting. The results show that, compared to the undulation amplitude and body wavelength, the undulation frequency has the greatest impact on swimming efficiency and energy costs, with low-frequency swimming being advantageous for efficient energy utilization. Additionally, the damping coefficient of the PTO system directly affects energy-harvesting efficiency, with higher energy-harvesting power achievable with an optimal PTO system parameter. Through a comprehensive analysis of energy costs and energy harvesting, it is concluded that the achievement of energy self-sufficiency for multi-joint robotic fish in marine environments is highly feasible. Full article
(This article belongs to the Section Marine Energy)
24 pages, 549 KiB  
Review
Claudins in Cancer: A Current and Future Therapeutic Target
by Caroline Hana, Nyein Nyein Thaw Dar, Michael Galo Venegas and Michel Vulfovich
Int. J. Mol. Sci. 2024, 25(9), 4634; https://doi.org/10.3390/ijms25094634 (registering DOI) - 24 Apr 2024
Abstract
Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. [...] Read more.
Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evidence shows improved outcomes when combining monoclonal antibodies against claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently, chimeric antigen receptor T-cells targeting claudin 18 are under investigation. In this review, we will discuss the major functions of claudins, their distribution in the normal as well as cancerous tissues, and their effect in cancer metastasis, with a special focus on the therapeutic targeting of claudins to improve cancer outcomes. Full article
13 pages, 1257 KiB  
Review
Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol
by Li Ma, Mengke Liu, Chuntong Liu, Huachang Zhang, Shude Yang, Jing An, Guiwu Qu, Shuling Song and Qizhi Cao
Molecules 2024, 29(9), 1943; https://doi.org/10.3390/molecules29091943 (registering DOI) - 24 Apr 2024
Abstract
Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and [...] Read more.
Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD. Full article
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19 pages, 1829 KiB  
Article
Impact of Rainfall on the Detection Performance of Non-Contact Safety Sensors for UAVs/UGVs
by Yasushi Sumi, Bong Keun Kim, Takuya Ogure, Masato Kodama, Naoki Sakai and Masami Kobayashi
Sensors 2024, 24(9), 2713; https://doi.org/10.3390/s24092713 (registering DOI) - 24 Apr 2024
Abstract
This study comprehensively investigates how rain and drizzle affect the object-detection performance of non-contact safety sensors, which are essential for the operation of unmanned aerial vehicles and ground vehicles in adverse weather conditions. In contrast to conventional sensor-performance evaluation based on the amount [...] Read more.
This study comprehensively investigates how rain and drizzle affect the object-detection performance of non-contact safety sensors, which are essential for the operation of unmanned aerial vehicles and ground vehicles in adverse weather conditions. In contrast to conventional sensor-performance evaluation based on the amount of precipitation, this paper proposes spatial transmittance and particle density as more appropriate metrics for rain environments. Through detailed experiments conducted under a variety of precipitation conditions, it is shown that sensor performance is significantly affected by the density of small raindrops rather than the total amount of precipitation. This finding challenges traditional sensor-evaluation metrics in rainfall environments and suggests a paradigm shift toward the use of spatial transmittance as a universal metric for evaluating sensor performance in rain, drizzle, and potentially other adverse weather scenarios. Full article
(This article belongs to the Special Issue Advanced UAV-Based Sensor Technologies)
20 pages, 1163 KiB  
Review
Co-Infections and Superinfections between HIV-1 and Other Human Viruses at the Cellular Level
by Chiara Acchioni, Silvia Sandini, Marta Acchioni and Marco Sgarbanti
Pathogens 2024, 13(5), 349; https://doi.org/10.3390/pathogens13050349 (registering DOI) - 24 Apr 2024
Abstract
Co-infection or superinfection of the host by two or more virus species is a common event, potentially leading to viral interference, viral synergy, or neutral interaction. The simultaneous presence of two or more viruses, even distantly related, within the same cell depends upon [...] Read more.
Co-infection or superinfection of the host by two or more virus species is a common event, potentially leading to viral interference, viral synergy, or neutral interaction. The simultaneous presence of two or more viruses, even distantly related, within the same cell depends upon viral tropism, i.e., the entry of viruses via receptors present on the same cell type. Subsequently, productive infection depends on the ability of these viruses to replicate efficiently in the same cellular environment. HIV-1 initially targets CCR5-expressing tissue memory CD4+ T cells, and in the absence of early cART initiation, a co-receptor switch may occur, leading to the infection of naïve and memory CXCR4-expressing CD4+ T cells. HIV-1 infection of macrophages at the G1 stage of their cell cycle also occurs in vivo, broadening the possible occurrence of co-infections between HIV-1 and other viruses at the cellular level. Moreover, HIV-1-infected DCs can transfer the virus to CD4+ T cells via trans-infection. This review focuses on the description of reported co-infections within the same cell between HIV-1 and other human pathogenic, non-pathogenic, or low-pathogenic viruses, including HIV-2, HTLV, HSV, HHV-6/-7, GBV-C, Dengue, and Ebola viruses, also discussing the possible reciprocal interactions in terms of virus replication and virus pseudotyping. Full article
10 pages, 250 KiB  
Article
(Non-Symmetric) Yetter–Drinfel’d Module Category and Invariant Coinvariant Jacobians
by Zhongwei Wang and Yong Wang
Symmetry 2024, 16(5), 515; https://doi.org/10.3390/sym16050515 (registering DOI) - 24 Apr 2024
Abstract
In this paper, we generalize the homomorphisms of modules over groups and Lie algebras as being morphisms in the category of (non-symmetric) Yetter–Drinfel’d modules. These module homomorphisms play a key role in the conjecture of Yau. Full article
(This article belongs to the Special Issue Symmetry/Asymmetry Study in Hopf-Type Algebras and Groups)
22 pages, 623 KiB  
Systematic Review
Revolutionizing the Pancreatic Tumor Diagnosis: Emerging Trends in Imaging Technologies: A Systematic Review
by Sabina Florina Șolea, Mihaela Cristina Brisc, Alexandra Orășeanu, Florian Ciprian Venter, Ciprian Mihai Brisc, Răzvan Mihai Șolea, Lavinia Davidescu, Amina Venter and Ciprian Brisc
Medicina 2024, 60(5), 695; https://doi.org/10.3390/medicina60050695 (registering DOI) - 24 Apr 2024
Abstract
Background and Objectives: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography serving as a primary investigative technique. A myriad of pancreatic pathologies, encompassing pancreatic neoplasia and a spectrum of inflammatory [...] Read more.
Background and Objectives: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography serving as a primary investigative technique. A myriad of pancreatic pathologies, encompassing pancreatic neoplasia and a spectrum of inflammatory diseases, are detectable through these imaging strategies. Nevertheless, the intricate anatomical confluence and the pancreas’s deep-seated topography render the visualization and accurate diagnosis of its pathologies a formidable endeavor. The objective of our paper is to review the best diagnostic imagistic tools for the pancreas. Materials and Methods: we have gathered several articles using Prisma guidelines to determine the best imagistic methods. The imperative of pancreatic scanning transcends its diagnostic utility, proving to be a pivotal element in a multitude of clinical specialties, notably surgical oncology. Within this domain, multidetector computed tomography (MDCT) of the pancreas holds the distinction of being the paramount imaging modality, endorsed for its unrivaled capacity to delineate the staging and progression of pancreatic carcinoma. In synergy with MDCT, there has been a notable advent of avant-garde imaging techniques in recent years. These advanced methodologies, including ultrasonography, endoscopic ultrasonography, contrast-enhanced ultrasonography, and magnetic resonance imaging (MRI) conjoined with magnetic resonance cholangiopancreatography (MRCP), have broadened the horizon of tumor characterization, offering unparalleled depth and precision in oncological assessment. Other emerging diagnostic techniques, such as elastography, also hold a lot of potential and promise for the future of pancreatic imaging. Fine needle aspiration (FNA) is a quick, minimally invasive procedure to evaluate lumps using a thin needle to extract tissue for analysis. It is less invasive than surgical biopsies and usually performed as an outpatient with quick recovery. Its accuracy depends on sample quality, and the risks include minimal bleeding or discomfort. Results, guiding further treatment, are typically available within a week. Elastography is a non-invasive medical imaging technique that maps the elastic properties and stiffness of soft tissue. This method, often used in conjunction with ultrasound or MRI, helps differentiate between hard and soft areas in tissue, providing valuable diagnostic information. It is particularly useful for assessing liver fibrosis, thyroid nodules, breast lumps, and musculoskeletal conditions. The technique is painless and involves applying gentle pressure to the area being examined. The resulting images show tissue stiffness, indicating potential abnormalities. Elastography is advantageous for its ability to detect diseases in early stages and monitor treatment effectiveness. The procedure is quick, safe, and requires no special preparation, with results typically available immediately. Results: The assembled and gathered data shows the efficacy of various techniques in discerning the nature and extent of neoplastic lesions within the pancreas. Conclusions: The most common imaging modalities currently used in diagnosing pancreatic neoplasms are multidetector computed tomography (MDCT), endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI), alongside new technologies, such as elastography. Full article
19 pages, 3398 KiB  
Article
4-Oxo-2-Nonenal- and Agitation-Induced Aggregates of α-Synuclein and Phosphorylated α-Synuclein with Distinct Biophysical Properties and Biomedical Applications
by Tie Wang, Weijin Liu, Qidi Zhang, Jie Jiao, Zihao Wang, Ge Gao and Hui Yang
Cells 2024, 13(9), 739; https://doi.org/10.3390/cells13090739 (registering DOI) - 24 Apr 2024
Abstract
α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson’s disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of [...] Read more.
α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson’s disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of different α-syn species could help to select suitable aggregates for diagnosis and elucidate the pathogenesis of diseases. Here, we characterized ONE-induced wild-type (WT) α-syn aggregates (OW), ONE-induced phosphorylated α-syn (p-α-syn) aggregates (OP), agitation-induced α-syn preformed fibrils (PFF), and agitation-induced p-α-syn preformed fibrils (pPFF). Thioflavin T (ThT) dying demonstrated that OW and OP had fewer fibrils than the PFF and pPFF. Transmission electron microscopy revealed that the lengths of PFF and pPFF were similar, but the diameters differed. OW and OP had more compact structures than PFF and pPFF. Aggregation of p-α-syn was significantly faster than WT α-syn. Furthermore, OW and OP were more sodium dodecyl sulfate-stable and proteinase K-resistant, suggesting greater stability and compactness, while aggregates of PFF and pPFF were more sensitive to proteinase K treatment. Both ONE- and agitation-induced aggregates were cytotoxic when added exogenously to SH-SY5Y cells with increasing incubation times, but the agitation-induced aggregates caused cell toxicity in a shorter time and more p-α-syn inclusions. Similarly, p-proteins were more cytotoxic than non-p-proteins. Finally, all four aggregates were used as standard antigens to establish sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that the recognition efficiency of OW and OP was more sensitive than that of PFF and pPFF. The OW- and OP-specific ELISA for detection of p-α-syn and α-syn in plasma samples of Thy1-α-syn transgenic mice showed that the content of aggregates could reflect the extent of disease. ONE and agitation induced the formation of α-syn aggregates with distinct biophysical properties and biomedical applications. Full article
(This article belongs to the Section Cellular Pathology)
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19 pages, 15195 KiB  
Article
Color and Luminance Separated Enhancement for Low-Light Images with Brightness Guidance
by Feng Zhang, Xinran Liu, Changxin Gao and Nong Sang
Sensors 2024, 24(9), 2711; https://doi.org/10.3390/s24092711 (registering DOI) - 24 Apr 2024
Abstract
Existing retinex-based low-light image enhancement strategies focus heavily on crafting complex networks for Retinex decomposition but often result in imprecise estimations. To overcome the limitations of previous methods, we introduce a straightforward yet effective strategy for Retinex decomposition, dividing images into colormaps and [...] Read more.
Existing retinex-based low-light image enhancement strategies focus heavily on crafting complex networks for Retinex decomposition but often result in imprecise estimations. To overcome the limitations of previous methods, we introduce a straightforward yet effective strategy for Retinex decomposition, dividing images into colormaps and graymaps as new estimations for reflectance and illumination maps. The enhancement of these maps is separately conducted using a diffusion model for improved restoration. Furthermore, we address the dual challenge of perturbation removal and brightness adjustment in illumination maps by incorporating brightness guidance. This guidance aids in precisely adjusting the brightness while eliminating disturbances, ensuring a more effective enhancement process. Extensive quantitative and qualitative experimental analyses demonstrate that our proposed method improves the performance by approximately 4.4% on the LOL dataset compared to other state-of-the-art diffusion-based methods, while also validating the model’s generalizability across multiple real-world datasets. Full article
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25 pages, 1107 KiB  
Review
RAF and MEK Inhibitors in Non-Small Cell Lung Cancer
by Christos Adamopoulos, Kostas A. Papavassiliou, Poulikos I. Poulikakos and Athanasios G. Papavassiliou
Int. J. Mol. Sci. 2024, 25(9), 4633; https://doi.org/10.3390/ijms25094633 (registering DOI) - 24 Apr 2024
Abstract
Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and [...] Read more.
Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and less in v-RAF murine sarcoma viral oncogene homolog B (BRAF) and mitogen-activated protein-kinase kinase (MEK), all key components of the RTK-RAS-mitogen-activated protein kinase (MAPK) pathway. Learning from melanoma, the identification of BRAFV600E substitution in NSCLC provided the rationale for the investigation of RAF and MEK inhibition as a therapeutic strategy. The regulatory approval of two RAF-MEK inhibitor combinations, dabrafenib–trametinib, in 2017, and encorafenib–binimetinib, in 2023, signifies a breakthrough for the management of BRAFV600E-mutant NSCLC patients. However, the almost universal emergence of acquired resistance limits their clinical benefit. New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
19 pages, 1200 KiB  
Article
Age-Related Conservation in Plant–Soil Feedback Accompanied by Ectomycorrhizal Domination in Temperate Forests in Northeast China
by Zhen Bai, Ji Ye, Shu-Fang Liu, Hai-Hong Sun, Zuo-Qiang Yuan, Zi-Kun Mao, Shuai Fang, Shao-Fen Long and Xu-Gao Wang
J. Fungi 2024, 10(5), 310; https://doi.org/10.3390/jof10050310 (registering DOI) - 24 Apr 2024
Abstract
This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant–soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant–soil traits by comparing [...] Read more.
This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant–soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant–soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant–soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant–soil consortia. Full article
(This article belongs to the Special Issue Soil Fungi and Their Role in Plant Growth)
21 pages, 815 KiB  
Article
Effects of Speleotherapy on Aerobiota: A Case Study from the Sežana Hospital Cave, Slovenia
by Rok Tomazin, Andreja Kukec, Viktor Švigelj, Janez Mulec and Tadeja Matos
Atmosphere 2024, 15(5), 518; https://doi.org/10.3390/atmos15050518 (registering DOI) - 24 Apr 2024
Abstract
Speleotherapy is one of the non-pharmacological methods for the treatment and rehabilitation of patients with chronic respiratory diseases, especially those with chronic obstructive pulmonary disease (COPD) and asthma. On the one hand, one of the alleged main advantages of speleotherapeutic caves is the [...] Read more.
Speleotherapy is one of the non-pharmacological methods for the treatment and rehabilitation of patients with chronic respiratory diseases, especially those with chronic obstructive pulmonary disease (COPD) and asthma. On the one hand, one of the alleged main advantages of speleotherapeutic caves is the low microbial load in the air and the absence of other aeroallergens, but on the other hand, due to the lack of comprehensive air monitoring, there is little information on the pristine and human-influenced aerobiota in such environments. The aim of this study was to assess the anthropogenic effects of speleotherapy on the air microbiota and to investigate its potential impact on human health in Sežana Hospital Cave (Slovenia). From May 2020 to January 2023, air samples were collected in the cave before and after speleotherapeutic activities using two different volumetric air sampling methods—impaction and impingement—to isolate airborne microbiota. Along with sampling, environmental data were measured (CO2, humidity, wind, and temperature) to explore the anthropogenic effects on the aerobiota. While the presence of patients increased microbial concentrations by at least 83.3%, other parameters exhibited a lower impact or were attributed to seasonal changes. The structure and dynamics of the airborne microbiota are similar to those in show caves, indicating anthropization of the cave. Locally, concentrations of culturable microorganisms above 1000 CFU/m3 were detected, which could have negative or unpredictable effects on the autochthonous microbiota and possibly on human health. A mixture of bacteria and fungi typically associated with human microbiota was found in the air and identified by MALDI-TOF MS with a 90.9% identification success rate. Micrococcus luteus, Kocuria rosea, Staphylococcus hominis, and Staphylococcus capitis were identified as reliable indicators of cave anthropization. Full article
(This article belongs to the Special Issue Bioaerosol Exposure and Its Risk Assessment)
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19 pages, 2447 KiB  
Article
Administration Routes and Doses of the Attenuated African Swine Fever Virus Strain PSA-1NH Influence Cross-Protection of Pigs against Heterologous Challenge
by Mikhail Vlasov, Irina Sindryakova, Dmitriy Kudryashov, Sergey Morgunov, Olga Kolbasova, Valentina Lyska, Sergey Zhivoderov, Elena Pivova, Vladimir Balyshev, Sanzhi Namsrayn, Timofey Sevskikh, Alexey Sereda and Denis Kolbasov
Animals 2024, 14(9), 1277; https://doi.org/10.3390/ani14091277 (registering DOI) - 24 Apr 2024
Abstract
African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF [...] Read more.
African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF is endemic, potentially featuring multiple circulating ASFV isolates. The investigation of non-hemadsorbing naturally attenuated isolates and laboratory recombinant strains with a deletion in the EP402R gene has attracted interest. Our study aimed to assess the impacts of various administration routes and doses of the naturally attenuated ASFV-PSA-1NH (immunotype IV, genotype I) isolate on the manifestation of clinical signs of ASF and the level of protection against the heterologous ASFV-Stavropol 01/08 strain (seroimmunotype VIII, genotype II). The results demonstrated that the intranasal administration of a low dose of ASFV-PSA-1NH to pigs minimized the clinical signs of ASF and established a high level of protection against the heterologous strain ASFV-Stavropol 01/08. Despite the challenges in standardizing the dosage for intranasal administration, this approach appears as a viable alternative in ASF vaccination. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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17 pages, 565 KiB  
Article
Splenic Elemental Composition of Breast Cancer-Suffering Rats Supplemented with Pomegranate Seed Oil and Bitter Melon Extract
by Małgorzata Białek, Tomasz Lepionka, Wiktoria Wojtak, Anna Ruszczyńska, Ewa Bulska, Marian Czauderna and Agnieszka Białek
Molecules 2024, 29(9), 1942; https://doi.org/10.3390/molecules29091942 (registering DOI) - 24 Apr 2024
Abstract
The aim of this study was to investigate how dietary modifications with pomegranate seed oil (PSO) and bitter melon aqueous extract (BME) affect mineral content in the spleen of rats both under normal physiological conditions and with coexisting mammary tumorigenesis. The diet of [...] Read more.
The aim of this study was to investigate how dietary modifications with pomegranate seed oil (PSO) and bitter melon aqueous extract (BME) affect mineral content in the spleen of rats both under normal physiological conditions and with coexisting mammary tumorigenesis. The diet of Sprague-Dawley female rats was supplemented either with PSO or with BME, or with a combination for 21 weeks. A chemical carcinogen (7,12-dimethylbenz[a]anthracene) was applied intragastrically to induce mammary tumors. In the spleen of rats, the selected elements were determined with a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). ANOVA was used to evaluate differences in elemental composition among experimental groups. Multivariate statistical methods were used to discover whether some subtle dependencies exist between experimental factors and thus influence the element content. Experimental factors affected the splenic levels of macroelements, except for potassium. Both diet modification and the cancerogenic process resulted in significant changes in the content of Fe, Se, Co, Cr, Ni, Al, Sr, Pb, Cd, B, and Tl in rat spleen. Chemometric analysis revealed the greatest impact of the ongoing carcinogenic process on the mineral composition of the spleen. The obtained results may contribute to a better understanding of peripheral immune organ functioning, especially during the neoplastic process, and thus may help develop anticancer prevention and treatment strategies. Full article
(This article belongs to the Special Issue Plants Extractions in Health Care)
19 pages, 10739 KiB  
Article
The Diversity of Freshwater Stygobiotic Crustaceans in the Republic of North Ossetia–Alania Provides New Evidence for the Existence of an Ancient Glacial Refugium in the North Caucasus Region
by Ivan N. Marin and Dmitry M. Palatov
Water 2024, 16(9), 1212; https://doi.org/10.3390/w16091212 (registering DOI) - 24 Apr 2024
Abstract
A review and partial revision of the diversity of freshwater stygobiotic crustaceans in the territory of the Republic of North Ossetia–Alania, in the North Caucasus, is presented here. Previously, two species of the genus Proasellus Dudich, 1925 (Isopoda, Asellidae), P. uallagirus Palatov & [...] Read more.
A review and partial revision of the diversity of freshwater stygobiotic crustaceans in the territory of the Republic of North Ossetia–Alania, in the North Caucasus, is presented here. Previously, two species of the genus Proasellus Dudich, 1925 (Isopoda, Asellidae), P. uallagirus Palatov & Sokolova, 2020 and P. irystonicus Palatov & Sokolova, 2020, and one species of the genus Niphargus Schiödte, 1849 (Amphipoda, Niphargidae), N. alanicus Marin & Palatov, 2021, were described from the hyporhean/underground habitats (hyporhea) in the area. However, further research using an integrative approach has revealed that only a single species of the genus Proasellus (P. uallagirus) is actually widely distributed in the hyporhean riverbed habitats in the area, while the diversity of the genus Niphargus is higher than previously known. Six more new Niphargus species— namely, N. ardonicus sp. nov., N. sadonicus sp. nov., N. fiagdonicus sp. nov., N. tschertschesovae sp. nov., N. osseticus sp. nov. and N. zeyensis sp. nov., were discovered from the various hypogean underground water sources (i.e., springs and seeps) and are described in this article. Their phylogenetic relationships with their congeners, as well as their ecology and known distribution, are discussed. Furthermore, molecular genetic analysis, with an interpretation of the estimated divergence time, suggests that the studied hyporheic/stygobiotic crustaceans started to diverge from related European and Balkan sister species during the Late Miocene, approximately 8–5.8 Mya, with the reduction in the Paratethys and the uplifting of the Caucasus Mountains. Local speciation was led by local geological processes and karst fragmentation during the Late Pliocene and Early Pleistocene periods, starting around 5.3 Mya. The obtained data suggest that the mountainous area of the North Ossetia–Alania could be considered as a post-Pliocene glacial refugium for subterranean and stygobiotic fauna—the first known for the North Caucasus region. Full article
(This article belongs to the Special Issue Biogeography and Speciation of Aquatic Organisms)
21 pages, 2076 KiB  
Article
Analysing the Evidence of the Effects of Climate Change, Air Pollutants, and Occupational Factors in the Appearance of Cataracts
by Lucía Echevarría-Lucas, José Mª Senciales-González and Jesús Rodrigo-Comino
Environments 2024, 11(5), 87; https://doi.org/10.3390/environments11050087 (registering DOI) - 24 Apr 2024
Abstract
Cataracts are ocular conditions characterized by the opacification of the natural lens within the eye, which develops gradually over time and can affect one or both eyes. This condition commonly results from age-related changes in the lens, but can also arise from various [...] Read more.
Cataracts are ocular conditions characterized by the opacification of the natural lens within the eye, which develops gradually over time and can affect one or both eyes. This condition commonly results from age-related changes in the lens, but can also arise from various factors. Cataract surgeries are expensive, particularly in states such as Spain, where they receive full support from the Spanish social welfare system. Despite a significant body of research on cataracts, few studies address the social and environmental factors triggering their development or consider the spatiotemporal evolution of their impacts. We analysed the incidence of cataracts in a southern region of Spain, differentiating between senile cataracts (those over 60 years old) and early cataracts (those between 15 and 59 years old). Twenty-one socio-economic, climate, and air pollution variables were statistically analysed using bivariate correlation, cluster analysis, and Geographic Information Systems. Eleven years of observation show a decadal increase in annually averaged maximum temperature and a decrease in annual precipitation, partially explaining the rising incidence of operable cataracts in the following year (r = 0.77 and −0.84, respectively; p < 0.05). Furthermore, early cataracts responded spatially to % agricultural employment (r = 0.85; p < 0.05) and moderately to maximum temperatures, insolation, and various constituents. Full article
(This article belongs to the Special Issue Air Quality, Health and Climate)
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20 pages, 3948 KiB  
Article
Early Identification and Dynamic Stability Evaluation of High-Locality Landslides in Yezhi Site Area, China by the InSAR Method
by Baoqin Lian, Daozheng Wang, Xingang Wang and Weijia Tan
Land 2024, 13(5), 569; https://doi.org/10.3390/land13050569 (registering DOI) - 24 Apr 2024
Abstract
In mountainous regions, high-locality landslides have the characteristics of a latent disaster process with a wide disaster range, which can easily cause large casualties. Therefore, early landslide identification and dynamic stability evaluation are significant. We first used multi-temporal synthetic aperture radar data to [...] Read more.
In mountainous regions, high-locality landslides have the characteristics of a latent disaster process with a wide disaster range, which can easily cause large casualties. Therefore, early landslide identification and dynamic stability evaluation are significant. We first used multi-temporal synthetic aperture radar data to detect potential landslides at Yezhi Site Area during the 2015–2020 period, identifying and mapping a total of 18 active landslides. The study area was found to have an average deformation rate between −15 and 10 mm/y during the period. Then, time series and spatiotemporal deformation characteristics of landslides were examined using interferogram stacking and small baseline interferometry techniques. The results show that the majority of the landslide deformations detected exhibit a periodic variation trend, and the study area was in a slow deformation state before 2017. Finally, combined with detection results, Google Earth optical images, and field investigations, it is concluded that the main factors affecting the time series deformation and spatial distribution of landslides in the study area are rainfall, geological factors, and engineering activities. The results of this study provide valuable technical references and support for early identification and dynamic stability evaluation of regional active landslides in complex terrain, especially for high-locality landslides. Full article
21 pages, 1004 KiB  
Article
Evaluating the Ceiling Gas Temperature in a Branched Tunnel Fire with a Sloped Mainline Region under Natural Ventilation
by Ning Lu, Xiaolin Yao, Jinming Yang and Youbo Huang
Fire 2024, 7(5), 152; https://doi.org/10.3390/fire7050152 (registering DOI) - 24 Apr 2024
Abstract
The effect of the mainline slope on the ceiling temperature profile in a branched tunnel has not been clarified nor included in existing models. Thus, in this paper, the numerical code was employed to investigate the induced airflow velocity and gas temperature beneath [...] Read more.
The effect of the mainline slope on the ceiling temperature profile in a branched tunnel has not been clarified nor included in existing models. Thus, in this paper, the numerical code was employed to investigate the induced airflow velocity and gas temperature beneath the ceiling in a branch tunnel with a sloped upstream mainline. The mainline slope varied from 1% to 7%, with an interval of 1%. Five fire power of 3 MW, 5 MW, 10 MW, 15 MW, and 20 MW are employed on each slope. The airflow velocity and the longitudinal temperature in the mainline tunnel are measured and analyzed. Results show that the stack effect obviously occurred, which caused longitudinal velocity to prevent the smoke reverse flow in the mainline. The induced airflow velocity in the upstream inclined mainline is higher with increasing slope, and the dimensionless velocity is normalized well by the proposed expression. The maximum ceiling temperature is independent of the mainline slope and correlated well by Q*2/3, but the effect of the mainline slope on temperature longitudinal decay is worth considering. Finally, a normalized expression for longitudinal temperature decay in an inclined mainline is proposed by taking the fire power and mainline slope into account. Full article
(This article belongs to the Special Issue Advance in Tunnel Fire Research)

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