Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)

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NS2B-D55E and NS2B-E65D Variations Are Responsible for Differences in NS2B-NS3 Protease Activities Between Japanese Encephalitis Virus Genotype I and III in Fluorogenic Peptide Model
Wahaab, Abdul; Zhang, Yan; Liu, Ke; Rasgon, Jason L.; Kang, Lei; Hameed, Muddassar; Li, Chenxi; Anwar, Muhammad Naveed; Zhang, Yanbing; Shoaib, Anam; Li, Beibei; Qiu, Yafeng; Wei, Jianchao; Ma, Zhiyong (MDPI, 2024-11-26)
Japanese encephalitis virus (JEV) NS2B-NS3 is a protein complex composed of NS3 proteases and an NS2B co-factor. The N-terminal protease domain (180 residues) of NS3 (NS3(pro)) interacts directly with a central 40-amino acid hydrophilic domain of NS2B (NS2B(H)) to form an active serine protease. In this study, the recombinant NS2B(H)-NS3(pro) proteases were prepared in E. coli and used to compare the enzymatic activity between genotype I (GI) and III (GIII) NS2B-NS3 proteases. The GI NS2B(H)-NS3(pro) was able to cleave the sites at the internal C, NS2A/NS2B, NS2B/NS3, and NS3/NS4A junctions that were identical to the sites proteolytically processed by GIII NS2B(H)-NS3(pro). Analysis of the enzymatic activity of recombinant NS2B(H)-NS3(pro) proteases using a model of fluorogenic peptide substrate revealed that the proteolytical processing activity of GIII NS2B(H)-NS3(pro) was significantly higher than that of GI NS2B(H)-NS3(pro). There were eight amino acid variations between GI and GIII NS2B(H)-NS3(pro), which may be responsible for the difference in enzymatic activities between GI and GIII proteases. Therefore, recombinant mutants were generated by exchanging the NS2B(H) and NS3(pro) domains between GI and GIII NS2B(H)-NS3(pro) and subjected to protease activity analysis. Substitution of NS2B(H) significantly altered the protease activities, as compared to the parental NS2B(H)-NS3(pro), suggesting that NS2B(H) played an essential role in the regulation of NS3(pro) protease activity. To further identify the amino acids responsible for the difference in protease activities, multiple substitution mutants including the individual and combined mutations at the variant residues 55 and 65 of NS2B(H) were generated and subjected to protease activity analysis. Replacement of NS2B-55 and NS2B-65 of GI to GIII significantly increased the enzymatic activity of GI NS2B(H)-NS3(pro) protease, whereas mutation of NS2B-55 and NS2B-65 of GIII to GI remarkably reduced the enzymatic activity of GIII NS2B(H)-NS3(pro) protease. Overall, these data demonstrated that NS2B-55 and NS2B-65 variations in the hydrophilic domain of NS2B co-contributed to the difference in NS2B(H)-NS3(pro) protease activities between GI and GIII. However, it will be crucial to explore these mutations in other in vivo and/or in vitro models. Collectively, these observations will be useful for understanding the replication of JEV GI and GIII viruses.
An Efficient Systematic Methodology for Noise and Vibration Analysis of a Reconfigurable Dynamic System Using Receptance Coupling Formulation
Hamedi, Behzad; Taheri, Saied (MDPI, 2024-11-29)
This study presents a generalized and systematic approach to modeling complex dynamic systems using Frequency-Based Substructuring (FBS). The aim is to develop an efficient method for system identification and subsystem decomposition, enabling the creation of reduced-order models for non-linear dynamic systems that are modular and reconfigurable. The methodology combines receptance (Frequency Response Function, FRF) properties from individual subsystems to predict the overall system’s response. This technique extends existing methods by Jetmundsen and D.D. Klerk and adapts them to subsystems with full degrees of freedom (DoFs), making it suitable for flexible and distributed structures. To demonstrate its effectiveness, the method is applied to vehicle noise and vibration analysis, where subsystems are initially treated as rigid bodies, but are later adapted to flexible characteristics. The results show that this hybrid approach accurately predicts system responses, offering significant advantages for NVH target setting when subsystem FRF matrices are sourced either from testing or numerical simulations. This methodology enhances the capability to model complex dynamic systems with improved precision and reduced computational cost. A comparison with traditional modeling techniques confirms the validity of the approach.
Modeling and Analysis of Dispersive Propagation of Structural Waves for Vibro-Localization
Ambarkutuk, Murat; Plassmann, Paul E. (MDPI, 2024-12-04)
The dispersion of structural waves, where wave speed varies with frequency, introduces significant challenges in accurately localizing occupants in a building based on vibrations caused by their movements. This study presents a novel multi-sensor vibro-localization technique that accounts for dispersion effects, enhancing the accuracy and robustness of occupant localization. The proposed method utilizes a model-based approach to parameterize key propagation phenomena, including wave dispersion and attenuation, which are fitted to observed waveforms. The localization is achieved by maximizing the joint likelihood of the occupant’s location based on sensor measurements. The effectiveness of the proposed technique is validated using two experimental datasets: one from a controlled environment involving an aluminum plate and the other from a building-scale experiment conducted at Goodwin Hall, Virginia Tech. Results for the proposed algorithm demonstrates a significant improvement in localization accuracy compared to benchmark algorithms. Specifically, in the aluminum plate experiments, the proposed technique reduced the average localization precision from 7.77 cm to 1.97 cm, representing a ∼74% improvement. Similarly, in the Goodwin Hall experiments, the average localization error decreased from 0.67 m to 0.3 m, with a ∼55% enhancement in accuracy. These findings indicate that the proposed approach outperforms existing methods in accurately determining occupant locations, even in the presence of dispersive wave propagation.
On the Approximation of Precision Matrices for Wide-Swath Altimetry
Yaremchuk, Max; Beattie, Christopher; Panteleev, Gleb (MDPI, 2024-12-05)
New observations of ocean surface topography obtained by wide-swath satellite interferometry require new capabilities to process spatially correlated errors in order to assimilate these data into numerical models. The sea surface height (SSH) variations have to be weighted against other types of assimilated data using information on their precision, as represented by the inverse of the SSH error covariance matrix R. The latter can be well approximated by a block-circulant (BC) structure and, therefore, allows numerically efficient implementation in operational data assimilation (DA) systems. In this note, we extend the technique of approximating R for wide-swath altimeters by including the uncertainties associated with the state of the atmosphere. It is shown that such an extension keeps the BC approximation error within acceptable (±10%) bounds in a wide range of environmental conditions and could be beneficial for improving the accuracy of SSH retrievals from wide-swath altimeter observations.
Temporal and Spatial Variations in Microplastic Concentrations in Small Headwater Basins in the Southern Blue Ridge Mountains, North Carolina, USA
Miller, Jerry; Barrett, Nathaniel; Love, Jason; Gray, Austin; Youker, Robert; Hall, Chloe; Meiri, Noa; Gaesser, Megan; Randall, Georgeanna; Jarrett, Reagan; Spafford, Juliet (MDPI, 2024-10-30)
Microplastics (MPs) are ubiquitous contaminants of emerging concern that require additional study in freshwater streams. We examined the spatial-temporal variations in MP concentrations and characteristics within two headwater basins in the Southern Appalachian Mountains of western North Carolina over ~1 year. Atmospheric samples were also collected to determine the significance of atmospheric MP deposition to these relatively small streams. MP concentrations in both basins were within the upper quartile of those reported globally, reaching maximum values of 65.1 MPs/L. Approximately 90% of MPs were fibers. MP composition was dominated by polystyrene, polyamides, and polyethylene terephthalate. Spatially, concentrations were highly variable and increased with development, indicating anthropogenic inputs from urbanized areas. MP concentrations were also elevated in forested tributary subbasins with limited anthropogenic activity, suggesting atmospheric deposition was an important MPs source. Significant atmospheric inputs are supported by high atmospheric depositional rates (ranging between 7.6 and 449.8 MPs/m²/day across our study sites) and similarities in morphology, color, and composition between atmospheric and water samples. Temporally, MP concentrations during storm events increased, decreased, or remained the same in comparison to base flows, depending on the site. The observed spatial and temporal variations in concentrations appear to be related to the complex interplay between precipitation and runoff intensities, channel transport characteristics, and MP source locations and contributions.
Combination Therapy Is Not Associated with Decreased Mortality in Infectious Endocarditis: A Systematic Review and Meta-Analysis
Farahani, Parisa; Ruffin, Felicia; Taherahmadi, Mohammad; Webster, Maren; Korn, Rachel E.; Cantrell, Sarah; Wahid, Lana; Fowler, Vance G.; Thaden, Joshua T. (MDPI, 2024-11-02)
Untreated infective endocarditis (IE) is uniformly fatal. The practice of combination antibiotic therapy for IE is recommended by treatment guidelines but largely unsupported by high-quality evidence. This study aimed to assess the efficacy of combination antibiotic therapy compared to monotherapy in IE through a systematic review and meta-analysis. We systematically searched MEDLINE, Embase, Cochrane, Web of Science, and CINAHL from inception to 29 July 2024. Studies reporting mortality outcomes of combination therapy versus monotherapy in adult patients with IE were included. Non-English papers and studies with less than 10 patients in the combination therapy group were excluded. Two reviewers independently assessed the studies and extracted relevant data. Summaries of odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated using random-effects models. Out of 4545 studies identified, 32 studies (involving 2761 patients) met the inclusion criteria for the meta-analysis. There was no significant difference in the risk of all-cause mortality between the monotherapy and combination therapy groups (OR = 0.90; 95% CI = 0.67–1.20). Similar results were observed in subgroup analyses based on mortality time points, bacterial species, publication date, and type of study. Studies conducted in Europe reported a statistically significant decrease in overall mortality risk with combination therapy (OR = 0.67; 95% CI = 0.51–0.89), though this result was driven entirely by a single outlier study. Combination antibiotic therapy in patients with IE was not associated with reduced mortality.
Spatial Transcriptomics and Single-Nucleus Multi-Omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development
Xu, Xiguang; Lin, Yu; Yin, Liduo; Serpa, Priscila da Silva; Conacher, Benjamin; Pacholec, Christina; Carvallo, Francisco; Hrubec, Terry; Farris, Shannon; Zimmerman, Kurt; Wang, Xiaobin; Xie, Hehuang (MDPI, 2024-11-07)
Background: Folate, an essential vitamin B9, is crucial for diverse biological processes, including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Objectives/Methods: Here, we employed a mouse model and spatial transcriptomic and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Results: Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Conclusions: Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.
Post-Operative Urinary Tract Infections After Radical Cystectomy: Incidence, Pathogens, and Risk Factors
Sandberg, Maxwell; Vancavage, Rachel; Refugia, Justin M.; Underwood, Gavin; Ye, Emily; Marie-Costa, Claudia; Rodriguez, Rainer; Prokopiou, Nicos; Bissette, Randall; Davis III, Ronald; Hemal, Ashok; Rodriguez, Alejandro R. (MDPI, 2024-11-12)
Background: The incidence of urinary tract infections (UTIs) after radical cystectomy (RC) with urinary diversion (UD), the typical pathogens, and associated patient risk factors have not been well documented. In this study, we examined the incidence of post-op UTIs after RC to identify associated risk factors. Methods: Single-center, retrospective case series of 386 patients with bladder cancer who underwent RC with UD between 2012 and 2024. The primary objective was UTI incidence, defined by the frequency of patients with urine culture with >10⁵ colony-forming units per high-powered field, spanning from post-op day 0 (POD0) to 90 days after discharge. Isolated pathogens were reported. Risk factors for UTIs were assessed. Results: The average age was 69 years old at surgery, and patients were predominantly male (80%). The cumulative incidence of post-op UTIs was 14%, among which 12 patients had more than one UTI. The UTI incidence was 2%, 8%, and 7% during the immediate post-op period, within 30 days, and within 31–90 days, respectively. Isolated pathogens included Escherichia coli (26%), Enterococcus faecalis (24%), Klebsiella pneumoniae (21%), and Pseudomonas species (21%). In the immediate post-op period, female sex was the only significant risk factor. At 31 to 90 days, cutaneous ureterostomy UD was the predominant risk factor for UTIs. For ileal conduit patients, those with a Wallace ureteral anastomosis were associated with UTI 31–90 days from discharge for RC. Conclusions: Our retrospective data suggests the incidence of UTIs and their causative pathogens after RC differ based on post-operative time points and vary according to different patient risk factors.
Site Preparation and Planting Strategies to Improve Native Forb Establishment in Pasturelands
Bellangue, David; Barney, Jacob; Flessner, Michael; Kubesch, Jonathan; O’Rourke, Megan; Tracy, Benjamin; Reid, John Leighton (MDPI, 2024-11-14)
Increasing the diversity of native forbs in pasturelands can benefit insect pollinator populations, which have been declining widely. Establishing native forbs into existing pasturelands can be challenging, however, and information about effective planting strategies in these systems is lacking. In this study, we evaluated several planting strategies to improve native forb establishment. Two field experiments were conducted in Virginia, USA in 2021 and 2022. Experiment 1 evaluated how six herbicide treatments and tillage affected establishment success when forbs were planted in summer or fall. Experiment 2 investigated how different seeding rates from 2.2 to 56 kg/ha and pre-seeding cold stratification affected forb establishment. In experiment 1, treatments using Roundup/glyphosate and tillage resulted in the most forb establishment. Planting in summer improved establishment with Roundup/glyphosate application. In experiment 2, native forb plant establishment was positively associated with seeding rate (p < 0.001), with a rate of 56 kg/ha resulting in almost 3x more forbs compared to the lowest seeding rate. Cold stratification also increased target plant establishment (p < 0.01), but these effects were inconsistent among species. Our results suggest that effective native forb establishment can be achieved through intensive site preparation with Roundup/glyphosate or tillage to suppress vegetation and planting at rates no higher than 11 kg/ha.
Analysis of Tire-Road Interaction: A Literature Review
Fathi, Haniyeh; El-Sayegh, Zeinab; Ren, Jing; El-Gindy, Moustafa (MDPI, 2024-11-14)
This paper presents a comprehensive literature review of the most popular and recent work on passenger and truck tires. Previous papers discuss a huge amount of work on the modeling of passenger car tires using finite element analysis. In addition, recent works on tire–road interaction and the validation of tires using experimental measurements have been described. Moreover, the history of the tire-road contact algorithms is explained. In addition, friction modeling that is implemented in tire–road interaction applications are discussed. Also, a summary of current state-of-the-art research work definitions and requirements of the tread rubber compound are covered from previous studies using various literature reviews and hyper-viscoelastic material models that are implemented for the tread top and the tread base rubber compound. Furthermore, the effect of tire temperature from previous works is presented here. Finally, this literature review also highlights the shortcomings of recent research work and describes the areas lacking in the literature.
Evaluation of Apparent Metabolizable Energy and Apparent Ileal Amino Acid Digestibility of Spirulina (Arthrospira platensis) in Broiler Chickens and Laying Hens
O’Lear Reid, Taylor K.; Gardner, Katherine E.; Paglia, Kayla L.; Ulans, Alexandra C. M.; Spierling, Ruth E.; Edwards, Mark S.; Lundquist, Tryg J.; McFarlane, Zach D.; Pokharel, Siroj; Bennett, Darin C. (MDPI, 2024-11-20)
Our study objective was to determine the apparent metabolizable energy (AME) and apparent ileal amino acid digestibility (AIAAD) of spirulina fed to broiler chickens and laying hens using the difference method. In both experiments, birds were either fed corn-soybean meal basal diets, containing no spirulina and formulated to provide the nutrient requirements of either broilers or layers, or fed test diets consisting of 25% spirulina and 75% of the appropriate basal diet. Titanium dioxide was added to all diets as an indigestible marker. The diets were fed to 10 replicate cages/treatment of broilers and 15 replicate cages/treatment of laying hens. The AME of spirulina for broilers was significantly lower (p < 0.05) (2368 ± 104 kcal/kg, as fed) than for laying hens (3144 ± 173 kcal/kg, as fed), suggesting bird type and age may influence energy utilization. The AIAAD of spirulina fed to broiler chickens did not differ from that of laying hens (p > 0.05), except for valine, alanine, and glycine, which were all significantly higher in laying hens (p < 0.05). Overall, the AIAAD for nonessential amino acids averaged 81.1%, with no significant difference between essential and nonessential amino acids. Differences in spirulina nutrient content cited in the literature support further research to determine the optimal inclusion of this alternative ingredient in broiler and layer diets.
ALMO: Active Learning-Based Multi-Objective Optimization for Accelerating Constrained Evolutionary Algorithms
Singh, Karanpreet; Kapania, Rakesh K. (MDPI, 2024-10-31)
In multi-objective optimization, standard evolutionary algorithms, such as NSGA-II, are computationally expensive, particularly when handling complex constraints. Constraint evaluations, often the bottleneck, require substantial resources. Pre-trained surrogate models have been used to improve computational efficiency, but they often rely heavily on the model’s accuracy and require large datasets. In this study, we use active learning to accelerate multi-objective optimization. Active learning is a machine learning approach that selects the most informative data points to reduce the computational cost of labeling data. It is employed in this study to reduce the number of constraint evaluations during optimization by dynamically querying new data points only when the model is uncertain. Incorporating machine learning into this framework allows the optimization process to focus on critical areas of the search space adaptively, leveraging predictive models to guide the algorithm. This reduces computational overhead and marks a significant advancement in using machine learning to enhance the efficiency and scalability of multi-objective optimization tasks. This method is applied to six challenging benchmark problems and demonstrates more than a 50% reduction in constraint evaluations, with varying savings across different problems. This adaptive approach significantly enhances the computational efficiency of multi-objective optimization without requiring pre-trained models.
Physical Cell Disruption Technologies for Intracellular Compound Extraction from Microorganisms
Zhao, Fujunzhu; Wang, Zhiwu; Huang, Haibo (MDPI, 2024-09-24)
This review focuses on the physical disruption techniques in extracting intracellular compounds, a critical step that significantly impacts yield and purity. Traditional chemical extraction methods, though long-established, face challenges related to cost and environmental sustainability. In response to these limitations, this paper highlights the growing shift towards physical disruption methods—high-pressure homogenization, ultrasonication, milling, and pulsed electric fields—as promising alternatives. These methods are applicable across various cell types, including bacteria, yeast, and algae. Physical disruption techniques achieve relatively high yields without degrading the bioactivity of the compounds. These techniques, utilizing physical forces to break cell membranes, offer promising extraction efficiency, with reduced environmental impacts, making them attractive options for sustainable and effective intracellular compound extraction. High-pressure homogenization is particularly effective for large-scale extracting of bioactive compounds from cultivated microbial cells. Ultrasonication is well-suited for small to medium-scale applications, especially for extracting heat-sensitive compounds. Milling is advantageous for tough-walled cells, while pulsed electric field offers gentle, non-thermal, and highly selective extraction. This review compares the advantages and limitations of each method, emphasizing its potential for recovering various intracellular compounds. Additionally, it identifies key research challenges that need to be addressed to advance the field of physical extractions.
Non-Nucleoside Lycorine-Based Analogs as Potential DENV/ZIKV NS5 Dual Inhibitors: Structure-Based Virtual Screening and Chemoinformatic Analysis
Rodríguez-Ararat, Adrián Camilo; Hayek-Orduz, Yasser; Vásquez, Andrés-Felipe; Sierra-Hurtado, Felipe; Villegas-Torres, María-Francisca; Caicedo-Burbano, Paola A.; Achenie, Luke E. K.; Barrios, Andrés Fernando González (MDPI, 2024-09-26)
Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (<−9.00 kcal/mol), surpassing that of RdRp-ribavirin (<−7.00 kcal/mol) along with promising ADMET score predictions (<4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. Our research highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.
Evaluation of Giant Knotweed Extract, Regalia, and Antibiotics in Control of Shoot Blight and Fire Blight Canker Phases on Apple
Boeckman, Nathanial; Borba, Matheus Correa; Aćimović, Srđan G. (MDPI, 2024-09-26)
We evaluated the effectiveness of three different treatment groups at managing apple shoot blight, and the resulting canker incidence and canker length on wood caused by Erwinia amylovora. Preventative foliar sprays or trunk injections of giant knotweed extract (Regalia), oxytetracycline (Arbor-OTC or FireLine + Regulaid), or streptomycin (Agri-mycin/FireWall + Regulaid) were applied to mature ‘Fuji’ trees. Regalia and oxytetracycline were ineffective at reducing shoot blight severity, showing poor disease reductions of 18.2% and 24.3% compared to untreated controls across both years. Streptomycin was effective at controlling shoot blight severity when applied as a spray application, reducing necrosis by up to 93.9% across both years. Canker incidence was also poorly reduced by Regalia and oxytetracycline with an average decrease of 33.3% and 52.4%, respectively. Again, spray applications of streptomycin were most effective at reducing canker incidence (95.2%). When present, canker length was best controlled by spray applications of streptomycin, showing an average reduction of 95.7%. The effectiveness of Regalia and oxytetracycline was poor, reducing canker length by only 30.4% and 43.5%, respectively. Trunk injections of Regalia were consistently less effective than spray applications. Compared to their spray application counterpart, Regalia injections were, on average, 12.5%, 26.3%, and 25.1% less effective at reducing shoot blight severity, canker incidence, and canker length, respectively. Injected Arbor-OTC was more effective than spray applications of oxytetracycline. On average, Arbor-OTC injections were up to 28.3%, 40.1%, and 30% more effective at reducing shoot blight severity, canker incidence, and canker length compared to spray applications. Overall, Regalia and oxytetracycline were not as effective as streptomycin at controlling fire blight. The search for organic antibiotic alternatives for shoot blight and canker control continues, as cankers are increasing in economic importance by causing bearing wood and young tree death.
Evolution and Innovations in Bone Marrow Cellular Therapy for Musculoskeletal Disorders: Tracing the Historical Trajectory and Contemporary Advances
Lana, José Fábio; de Brito, Gabriela Caponero; Kruel, André; Brito, Benjamim; Santos, Gabriel Silva; Caliari, Carolina; Salamanna, Francesca; Sartori, Maria; Barbanti Brodano, Giovanni; Costa, Fábio Ramos; Jeyaraman, Madhan; Dallo, Ignácio; Bernaldez, Pedro; Purita, Joseph; Andrade, Marco Antonio Percope de; Everts, Peter Albert (MDPI, 2024-09-28)
Bone marrow cellular therapy has undergone a remarkable evolution, significantly impacting the treatment of musculoskeletal disorders. This review traces the historical trajectory from early mythological references to contemporary scientific advancements. The groundbreaking work of Friedenstein in 1968, identifying fibroblast colony-forming cells in bone marrow, laid the foundation for future studies. Caplan’s subsequent identification of mesenchymal stem cells (MSCs) in 1991 highlighted their differentiation potential and immunomodulatory properties, establishing them as key players in regenerative medicine. Contemporary research has focused on refining techniques for isolating and applying bone marrow-derived MSCs. These cells have shown promise in treating conditions like osteonecrosis, osteoarthritis, and tendon injuries thanks to their ability to promote tissue repair, modulate immune responses, and enhance angiogenesis. Clinical studies have demonstrated significant improvements in pain relief, functional recovery, and tissue regeneration. Innovations such as the ACH classification system and advancements in bone marrow aspiration methods have standardized practices, improving the consistency and efficacy of these therapies. Recent clinical trials have validated the therapeutic potential of bone marrow-derived products, highlighting their advantages in both surgical and non-surgical applications. Studies have shown that MSCs can reduce inflammation, support bone healing, and enhance cartilage repair. However, challenges remain, including the need for rigorous characterization of cell populations and standardized reporting in clinical trials. Addressing these issues is crucial for advancing the field and ensuring the reliable application of these therapies. Looking ahead, future research should focus on integrating bone marrow-derived products with other regenerative techniques and exploring non-surgical interventions. The continued innovation and refinement of these therapies hold promise for revolutionizing the treatment of musculoskeletal disorders, offering improved patient outcomes, and advancing the boundaries of medical science.
Long-Term Effects of Nitrogen and Tillage on Yields and Nitrogen Use Efficiency in Irrigated Corn
Delgado, Jorge A.; D’Adamo, Robert E.; Villacis, Alexis H.; Halvorson, Ardell D.; Stewart, Catherine E.; Floyd, Bradley A.; Del Grosso, Stephen J.; Manter, Daniel K.; Alwang, Jeffrey R. (MDPI, 2024-10-07)
By tonnage, corn (Zea mays L.) is the #1 crop produced globally, and recent research has suggested that no-till (NT) systems can lead to reduced yields of this important crop. Additionally, there is a lack of long-term data about the effects of tillage and N management on cropping systems. Corn is the most nitrogen (N)-fertilized crop in the USA, and N losses to the environment contribute to significant impacts on air and water quality. We conducted long-term studies on conventional tillage (CT) and conservation tillage systems, such as strip tillage (ST) and NT, under different N rates. We found that immediately after conversion to NT, yields from NT were significantly lower than yields from CT (p < 0.1), but after five years of NT, the NT yields were 1.5% higher than the CT yields (p < 0.1). Initially, the NT yields were lower than the ST (p < 0.01), but after seven years of NT, the NT yields were comparable to ST grain yields. Although the total aboveground N uptake with NT immediately after conversion to NT was lower than with CT and ST, these differences were not significant in the long run. The nitrogen use efficiency (NUE) with NT increased over time. The present work highlights the importance of long-term research for determining the cumulative impacts of best management practices such as NT. We found that NT becomes a more viable practice after five or seven years of implementation, demonstrating the high importance of long-term research.
Glycosphingolipids in Cardiovascular Disease: Insights from Molecular Mechanisms and Heart Failure Models
Huang, Sarah; Abutaleb, Karima; Mishra, Sumita (MDPI, 2024-10-08)
This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVDs), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.
Land Cover Mapping in East China for Enhancing High-Resolution Weather Simulation Models
Ma, Bingxin; Shao, Yang; Yang, Hequn; Lu, Yiwen; Gao, Yanqing; Wang, Xinyao; Xie, Ying; Wang, Xiaofeng (MDPI, 2024-10-10)
This study was designed to develop a 30 m resolution land cover dataset to improve the performance of regional weather forecasting models in East China. A 10-class land cover mapping scheme was established, reflecting East China’s diverse landscape characteristics and incorporating a new category for plastic greenhouses. Plastic greenhouses are key to understanding surface heterogeneity in agricultural regions, as they can significantly impact local climate conditions, such as heat flux and evapotranspiration, yet they are often not represented in conventional land cover classifications. This is mainly due to the lack of high-resolution datasets capable of detecting these small yet impactful features. For the six-province study area, we selected and processed Landsat 8 imagery from 2015–2018, filtering for cloud cover. Complementary datasets, such as digital elevation models (DEM) and nighttime lighting data, were integrated to enrich the inputs for the Random Forest classification. A comprehensive training dataset was compiled to support Random Forest training and classification accuracy. We developed an automated workflow to manage the data processing, including satellite image selection, preprocessing, classification, and image mosaicking, thereby ensuring the system’s practicality and facilitating future updates. We included three Weather Research and Forecasting (WRF) model experiments in this study to highlight the impact of our land cover maps on daytime and nighttime temperature predictions. The resulting regional land cover dataset achieved an overall accuracy of 83.2% and a Kappa coefficient of 0.81. These accuracy statistics are higher than existing national and global datasets. The model results suggest that the newly developed land cover, combined with a mosaic option in the Unified Noah scheme in WRF, provided the best overall performance for both daytime and nighttime temperature predictions. In addition to supporting the WRF model, our land cover map products, with a planned 3–5-year update schedule, could serve as a valuable data source for ecological assessments in the East China region, informing environmental policy and promoting sustainability.
State of the Field: Cytotoxic Immune Cell Responses in C. neoformans and C. deneoformans Infection
Okafor, Elizabeth C.; Nielsen, Kirsten (MDPI, 2024-10-12)
Cryptococcus neoformans is an environmental pathogen that causes life-threatening disease in immunocompromised persons. The majority of immunological studies have centered on CD4⁺ T-cell dysfunction and associated cytokine signaling pathways, optimization of phagocytic cell function against fungal cells, and identification of robust antigens for vaccine development. However, a growing body of literature exists regarding cytotoxic cells, specifically CD8⁺ T-cells, Natural Killer cells, gamma/delta T-cells, NK T-cells, and Cytotoxic CD4⁺ T-cells, and their role in the innate and adaptive immune response during C. neoformans and C. deneoformans infection. In this review, we (1) provide a comprehensive report of data gathered from mouse and human studies on cytotoxic cell function and phenotype, (2) discuss harmonious and conflicting results on cellular responses in mice models and human infection, (3) identify gaps of knowledge in the field ripe for exploration, and (4) highlight how innovative immunological tools could enhance the study of cytotoxic cells and their potential immunomodulation during cryptococcosis.

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