Search Results (197)

Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with disrupted lipid metabolism. This study aimed to uncover novel molecular subtypes and biomarkers by integrating sphingolipid metabolism-related genes (SMGs) with machine learning approaches. Using data from the GEO and GeneCards databases, 29 UC-related SMGs were identified. Consensus clustering was employed to define distinct molecular subtypes of UC, and a diagnostic model was developed through various machine learning algorithms. Further analyses—including functional enrichment, transcription factor prediction, single-cell localization, potential drug screening, molecular docking, and molecular dynamics simulations—were conducted to investigate the underlying mechanisms and therapeutic prospects of the identified genes in UC. The analysis revealed two molecular subtypes of UC: C1 (metabolically dysregulated) and C2 (immune-enriched). A diagnostic model based on three key genes demonstrated high accuracy in both the training and validation cohorts. Moreover, the transcription factor FOXA2 was predicted to regulate the expression of all three genes simultaneously. Notably, mebendazole and NVP-TAE226 emerged as promising therapeutic agents for UC. In conclusion, SMGs are integral to UC molecular subtyping and immune microenvironment modulation, presenting a novel framework for precision diagnosis and targeted treatment of UC. Full article

The tip-of-the-tongue (TOT) phenomenon is characterized by a temporary inability to retrieve a word despite a strong sense of familiarity. While extensive research has linked phonological processing to TOT, the exact nature of this relationship remains debated. The “blocking hypothesis” suggests that the retrieval of target words is interfered with by phonological neighbors, whereas the “transmission deficit hypothesis” posits that TOT arises from insufficient phonological activation of the target words. This study revisited this issue by examining the relationship between the microstructural integrity of the phonological processing brain network and TOT, utilizing graph-theoretical analyses of neuroimaging data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), which included diffusion tensor imaging (DTI) data from 576 participants aged 18–87. The results revealed that global efficiency and mean degree centrality of the phonological processing network positively predicted TOT rates. At the nodal level, the nodal efficiency of the bilateral posterior superior temporal gyrus and the clustering coefficient of the left premotor cortex positively predicted TOT rates, while the degree centrality of the left dorsal superior temporal gyrus (dSTG) and the clustering coefficient of the left posterior supramarginal gyrus (pSMG) negatively predicted TOT rates. Overall, these findings suggest that individuals with a more enriched network of phonological representations tend to experience more TOTs, supporting the blocking hypothesis. Additionally, this study highlights the roles of the left dSTG and pSMG in facilitating word retrieval, potentially reducing the occurrence of TOTs. Full article

Cardiomyocytes, similarly to cells in various tissues, are responsive to mechanical stress of all types, which is reflected in the significant alterations to their electrophysiological characteristics. This phenomenon, known as mechanoelectric feedback, is based on the work of mechanically gated channels (MGCs) and mechano-sensitive channels (MSCs). Since microgravity (MG) in space, as well as simulated microgravity (SMG), changes the morphological and physiological properties of the heart, it was assumed that this result would be associated with a change in the expression of genes encoding MGCs and MSCs, leading to a change in the synthesis of channel proteins and, ultimately, a change in channel currents during cell stretching. In isolated ventricular cardiomyocytes of rats exposed to SMG for 14 days, the amount of MGCs and MSCs gene transcripts was studied using the RNA sequencing method by normalizing the amount of “raw” reads using the Transcripts Per Kilobase Million (TPM) method. Changes in the level of channel protein, using the example of the MGCs TRPM7, were assessed by the Western blot method, and changes in membrane ion currents in the control and during cardiomyocyte stretching were assessed by the patch-clamp method in the whole-cell configuration. The data obtained demonstrate that SMG results in a multidirectional change in the expression of genes encoding various MGCs and MSCs. At the same time, a decrease in the TPM of the MGCs TRPM7 gene leads to a decrease in the amount of TRPM7 protein. The resulting redistribution in the synthesis of most channel proteins leads to a marked decrease in the sensitivity of the current through MGCs to cell stretching and, ultimately, to a change in the functioning of the heart. Full article

Small (monomeric) GTP-binding proteins (smgs; Cdc42 and Rac1) play requisite roles in islet beta cell function, including glucose-stimulated insulin secretion. In addition, emerging evidence suggests that sustained (constitutive) activation of smgs (e.g., Rac1) culminates in the genesis of islet beta cell dysfunction under the duress of chronic hyperglycemia. It is noteworthy that functions (i.e., activation–deactivation) of smgs in many cells, including the islet beta cell, have been shown to be under the regulatory control of at least three factors, namely the guanine nucleotide exchange factors (GEFs), the GTPase-activating proteins (GAPs), and the GDP-dissociation inhibitors (GDIs). The overall objective of this review is to highlight our current understanding of the regulatory roles of the RhoGDIβ-Rac1-CARD9 signalome in the pathology of beta cell dysfunction under chronic hyperglycemic stress. For brevity, this review is structured by an overview of smgs and their regulatory proteins/factors in the beta cell, followed by a discussion of potential roles of the RhoGDIβ-Rac1-CARD9 axis in the onset of cellular dysfunction under the duress of metabolic stress. Overall conclusions, potential knowledge gaps, and opportunities for future research in this field of islet biology are highlighted in the last section. Full article

Sonomyography (SMG) is a method of controlling upper-limb prostheses through an innovative human–machine interface by monitoring forearm muscle activity through ultrasonic imaging. Over the past two decades, SMG has shown promise, achieving over 90% accuracy in classifying hand gestures when combined with artificial intelligence, making it a viable alternative to electromyography (EMG). However, up to now, there are few reports of a system integrating SMG together with a prosthesis for testing on amputee subjects to demonstrate its capability in relation to daily activities. In this study, we developed a highly efficient human–machine interface algorithm for controlling a prosthetic hand with 6-DOF using a wireless and wearable ultrasound imaging probe. We first evaluated the accuracy of our model in classifying nine different hand gestures to determine its reliability and precision. The results from the offline study, which included ten healthy participants, indicated that nine different hand gestures could be classified with a success rate of 100%. Additionally, the developed controlling system was tested in real-time experiments on two amputees, using a variety of hand function test kits. The results from the hand function tests confirmed that the prosthesis, controlled by the SMG system, could assist amputees in performing a variety of hand movements needed in daily activities. Full article

Plants dynamically regulate ions in the tree to defend against abiotic stresses such as drought and saline-alkali, However, it is not clear how ‘Junzao’ jujube regulates ions to maintain a normal life cycle under saline-alkali stress. Therefore, in this study, the roots of 10-year old steer jujube trees were watered using a saline and alkaline gradient solution simulating the main salt (NaCl) and alkali (NaHCO₃) of Aral with NaCl:NaHCO₃ = 3:1 gradient of 0, 60, 180, and 300 mM, and three jujube trees with uniform growth were taken as samples in each treatment plot, and the ion contents of potassium (K), sodium (Na), calcium (Ca), magnesium (Mg), iron (Fe), manganese (Mn), zinc (Zn) and carbon (C) in each organ of the fruit at the dot red period (S1) and full-red period (S2) were determined, in order to elucidate the relationship between physiological adaptation mechanisms of saline-alkali tolerance and the characteristics of mineral nutrient uptake and utilisation in jujube fruit. The results showed that under saline-alkali stress, Na was stored in large quantities in the roots, Ca and Mg in the perennial branches at S1, Na and Fe in the leaves at S2, and K, Mg and Mn in the perennial branches. There was no significant difference in the distribution of C content in various organs of ‘Junzao’. Compared with CK (0 mM), under salinity stress, the K content in the leaves was significantly reduced at S1 and S2, and the K/Na ratios remained > 1.0. At S2, under medium and high concentrations of saline-alkali stress (180–300 mM), the K/Na is less than 1, and the ionic homeostasis was disrupted, and the leaves die and fall off, and the Na is excreted from the body. The selective transport coefficients SK/Na, SCa/Na and SMg/Na from root to leaf showed a downward trend at S1, but still maintained positive transport capacity. At S2, this stage is close to leaf fall, the nutrient transport coefficient is less than 1, and a large amount of nutrients are returned to the perennial branches and roots occurred. These results indicated that the mechanism of nutrient regulation and salt tolerance in jujube trees was different at different growth stages. Full article

Due to the intermittent and uncertain nature of emerging renewable energy sources in the modern power grid, the level of dispatchable power sources has been reduced. The contemporary power system is attempting to address this by investing in energy storage within the context of standalone microgrids (SMGs), which can operate in an island mode and off-grid. While renewable-rich SMGs can facilitate a higher level of renewable energy penetration, they also have more reliability issues compared to conventional power systems due to the intermittency of renewables. When an SMG system needs to be upgraded for reliability improvement, the cost of that reliability improvement should be divided among diverse customer sectors. In this research, we present four distinct approaches along with comprehensive simulation outcomes to address the problem of allocating reliability costs. The central issue in this study revolves around determining whether all consumers should bear an equal share of the reliability improvement costs or if these expenses should be distributed among them differently. When an SMG system requires an upgrade to enhance its reliability, it becomes imperative to allocate the associated costs among various customer sectors as equitably as possible. In our investigation, we model an SMG through a simulation experiment, involving nine distinct customer sectors, and utilize their hourly demand profiles for an entire year. We explore how to distribute the total investment cost of reliability improvement to each customer sector using four distinct methods. The first two methods consider the annual and seasonal peak demands in each industry. The third approach involves an analysis of Loss of Load (LOL) events and determining the hourly load requirements for each sector during these events. In the fourth approach, we employ the Technique for Order of Preference by Similarity to the Ideal Solution (TOPSIS) technique. The annual peak demand approach resulted in the educational sector bearing the highest proportion of the reliability improvement cost, accounting for 21.90% of the total burden. Similarly, the seasonal peak demand approach identified the educational sector as the most significant contributor, though with a reduced share of 15.44%. The normalized average demand during Loss of Load (LOL) events also indicated the same sector as the highest contributor, with 12.34% of the total cost. Lastly, the TOPSIS-based approach assigned a 15.24% reliability cost burden to the educational sector. Although all four approaches consistently identify the educational sector as the most critical in terms of its impact on system reliability, they yield different cost allocations due to variations in the methodology and weighting of demand characteristics. The underlying reasons for these differences, along with the practical implications and applicability of each method, are comprehensively discussed in this research paper. Based on our case study findings, we conclude that the education sector, which contributes more to LOL events, should bear the highest amount of the Cost of Reliability Improvement (CRI), while the hotel and catering sector’s share should be the lowest percentage. This highlights the necessity for varying reliability improvement costs for different consumer sectors. Full article

In a smart microgrid (SMG) system that deals with unpredictable loads and incorporates fluctuating solar and wind energy, it is crucial to have an efficient method for controlling frequency in order to balance the power between generation and load. In the last decade, cyberattacks have become a growing menace, and SMG systems are commonly targeted by such attacks. This study proposes a framework for the frequency management of an SMG system using an innovative combination of a smart controller (i.e., the Fuzzy Logic Controller (FLC)) with three conventional cascaded controllers, including Fractional-Order PI (FOPI), Tilt Integral Fractional Derivative (TID^μ), and Proportional Integral Derivative Acceleration (PIDA). The recently released Eel and Grouper Optimization (EGO) algorithm is used to fine-tune the parameters of the proposed controller. This algorithm was inspired by how eels and groupers work together and find food in marine ecosystems. The Integral Time Squared Error (ITSE) of the frequency fluctuation (ΔF) around the nominal value is used as an objective function for the optimization process. A diesel engine generator (DEG), renewable sources such as wind turbine generators (WTGs), solar photovoltaics (PVs), and storage components such as flywheel energy storage systems (FESSs) and battery energy storage systems (BESSs) are all included in the SMG system. Additionally, electric vehicles (EVs) are also installed. In the beginning, the supremacy of the adopted EGO over the Gradient-Based Optimizer (GBO) and the Smell Agent Optimizer (SAO) can be witnessed by taking into consideration the optimization process of the recommended regulator’s parameters, in addition to the optimum design of the membership functions of the fuzzy logic controller by each of these distinct algorithms. The subsequent phase showcases the superiority of the proposed EGO-based FFOPI-TID^μ-PIDA structure compared to EGO-based conventional structures like PID and EGO-based intelligent structures such as Fuzzy PID (FPID) and Fuzzy PD-(1 + PI) (FPD-(1 + PI)); this is across diverse symmetry operating conditions and in the presence of various cyberattacks that result in a denial of service (DoS) and signal transmission delays. Based on the simulation results from the MATLAB/Simulink R2024b environment, the presented control methodology improves the dynamics of the SMG system by about 99.6% when compared to the other three control methodologies. The fitness function dropped to 0.00069 for the FFOPI-TID^μ-PIDA controller, which is about 200 times lower than the other controllers that were compared. Full article

Introduction and objective: Assessment of α-synuclein (αSyn) seed amplification assays (αSyn-SAA) accuracy in distinguishing Parkinson’s disease (PD) from controls using cerebrospinal fluid (CSF), blood, skin, extracellular vesicles (ECV), saliva, olfactory mucosa (OM), gastrointestinal tract (GIT), and submandibular gland (SMG). Methodology: PubMed was searched for articles from 2010 to January 2025. The quality assessment used robvis. Diagnostic values with a 95% confidence interval (CI) were obtained. Z-test, Wald CI, and ANOVA were performed. Diagnostic odds ratio (DOR) was used. Results: αSyn-SAAs showed strong diagnostic performance in distinguishing PD from controls across various tissue and fluid types. Overall, αSyn-SAAs demonstrated high sensitivity (86%) and specificity (92%). Among all biomatrices, CSF, skin, blood, and ECV yielded the highest diagnostic accuracy, with sensitivity and specificity approaching or exceeding 90%. In contrast, saliva, oral mucosa, and gastrointestinal tract samples showed more modest sensitivity, though specificity remained relatively high. ECV, CSF, skin, and blood matrices also demonstrated the highest DOR, supporting their potential clinical utility. Conclusions: ECV and blood warrant priority in αSyn-SAA for high accuracy and minimal invasiveness, while GIT, OM, and oral samples show limited utility; saliva and SMG need refinement. Full article

The nonsense-mediated mRNA decay (NMD) is extensively involved in physiological, pathological, and stress response processes in humans and plants. However, the NMD in phytopathogenic fungi has not yet been thoroughly investigated. In this study, we identified and performed domain analysis on the core components of the NMD in ten globally widespread phytopathogenic fungi that cause significant economic losses. The core components of NMD in these fungi exhibit high similarity to their homologous genes in humans, while also possessing certain specificities. The core factors of the NMD, including the Up-frameshift factors (UPFs) and the exon junction complex (EJC), are generally conserved among phytopathogenic fungi. Notably, suppressors with morphological effects on genitalia (SMG) genes are absent in these fungi, which bears some similarity to the EJC-independent NMD degradation mechanism observed in Saccharomyces cerevisiae. Interestingly, plant pathogenic fungi contain highly homologous genes of the EJC complex, suggesting the presence of an EJC-dependent NMD degradation mechanism. In summary, our findings demonstrate that NMD are prevalent in plant pathogenic fungi, providing a research foundation for subsequent studies on NMD in their growth, development, and involvement in pathogenic processes. Full article

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. Microgravity has become a useful tool in cancer research due to its effects on various cellular processes. This paper presents a deep molecular and proteomic analysis investigating cell growth, the modulation of cytokeratins, and proteins related to apoptosis, cellular metabolism, and protein synthesis after TSA treatment in simulated microgravity (SMG)-exposed PaCa44 3D cells. Our analysis concerns the effects of TSA treatment on cell proliferation: the impairment of the cell cycle with the downregulation of proteins involved in Cdc42 signaling and G1/G2- and G2/M-phase transitions. Thus, we observed modification of survival pathways and proteins related to autophagy and apoptosis. We also observed changes in proteins involved in the regulation of transcription and the repair of damaged DNA. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways. Full article

Rice blast caused by Magnaporthe oryzae (MOR) reigns as the top-most devastating disease affecting global rice production. Pattern-triggered immunity (PTI) is crucial for mitigating plant responses to pathogens. However, the transcriptional dynamics of PTI-related genes in rice response to MOR infection remain largely unexplored. In this study, we performed a meta-analysis of 201 RNA sequencing and 217 microarray datasets to investigate the transcriptional dynamics of rice under MOR infection at various infection stages. The transcriptional dynamics of extracellular/cytoplasmic receptor kinase genes (RLKs, RLCKs, WAKs) and downstream signaling intermediates, including mitogen-activated protein kinases (MAPKs) and Ca²⁺-related signaling genes, were identified as immunity hubs for PTI. Extracellular/cytoplasmic receptors were predominantly induced, in contrast to a marked decrease in the repression of these genes. Notably, a maximum of 141 and 154 receptor-based genes were frequently induced from the microarray and RNA-seq datasets, respectively. Moreover, 31 genes were consistently induced across all the transcriptomic profiles, highlighting their pivotal role in PTI-activating immunity regulation in rice under MOR stress. Furthermore, protein–protein interaction (PPI) analysis revealed that cytoplasmic receptor-based genes (RLCKs) and MAPK(K)s were highly interconnected. Among them, four core MAPKK genes, including SMG1, MKK1, MKK6, and MPKK10.2, were identified as the most frequently interconnected with receptor-based genes or other MAPKs under MOR infection, suggesting their critical role as intermediates during downstream signaling networks in response to MOR infection. Together, our comprehensive analysis provides insights into the transcriptional dynamics of receptor-based genes and downstream signaling intermediates as core PTI-related genes that can play crucial roles in modulating rice immune responses to MOR infection. Full article

Hydrogels have become indispensable in biomedical research and regenerative therapies due to their high water content, tissue-like mechanics, and tunable biochemical properties. However, their behavior under altered gravitational conditions—particularly simulated microgravity (SMG)—presents a frontier of challenges and opportunities that remain underexplored. This comprehensive review provides a detailed comparative analysis of hydrogel performance in normal gravity versus SMG environments, focusing on the structural, physicochemical, and thermodynamic parameters that govern their functionality. We critically examine how microgravity influences polymer network formation, fluid dynamics, swelling behavior, mechanical stability, and degradation kinetics. SMG disrupts convection, sedimentation, and phase separation, often leading to inhomogeneous crosslinking and altered diffusion profiles. These changes can compromise hydrogel uniformity, anisotropy, and responsiveness, which are essential for biomedical applications such as drug delivery, tissue regeneration, and biosensing. To address these limitations, we propose a thermodynamic framework that integrates osmotic pressure regulation, entropy-driven swelling, and pressure–temperature control to enhance hydrogel stability and functionality in low-gravity environments. The integration of predictive modeling approaches—including finite element simulations, phase-field models, and swelling kinetics—provides a robust pathway to design space-adapted hydrogel systems. The review also outlines future directions for optimizing hydrogel platforms in extraterrestrial settings, advocating for synergistic advances in material science, biophysics, and space health. These insights offer a strategic foundation for the rational development of next-generation hydrogel technologies tailored for long-duration space missions and planetary biomedical infrastructure. Full article

Background: Sjögren’s syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. In this study, non-obese diabetic (NOD) mice were used as an animal model for studying SS, to evaluate the optimal administration route and dose range of dental pulp stem cells (DPSCs) in the treatment of sialadenitis caused by SS. Methods: Different doses of DPSCs were transplanted into the submandibular glands (SMGs) of 14-week-old NOD mice through two different methods: injection or retrograde perfusion through the catheter orifice into the SMG. At 21 weeks of age, the saliva flow rate (SFR), ectopic lymphocytes, and CD4⁺ T-cell infiltration were measured. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the glandular tissues were also quantitatively detected. Results: Compared with untreated and PBS-injected controls, different-dose groups of the two administration methods showed an increased saliva flow rate of NOD mice to varying degrees, reduced infiltration of lymphocytes and CD4⁺ T cells in the SMG, and decreased IFN-γ/TNF-α levels. Finally, we compared these two administration routes and found that the perfusion of 2 × 10⁵ DPSCs presents good therapeutic effects. Conclusions: DPSC perfusion through the catheter orifice is a simple and effective treatment method, which is worthy of further investigation through clinical trials. Full article