Search Results (8,361)

Protein condensates and filaments are both intracellular structures characterized by their ability to facilitate specific biological functions. Their formation is primarily driven by phase separation, which can be elucidated by fluorescence microscopy or electron microscopy. Here we summarize the main studies on protein condensates and filaments organized according to the techniques used, including fluorescence methods like localization screening, fluorescence co-localization spectroscopy, methods based on photobleaching, super-resolution imaging, and electron methods including negative-stain electron microscopy and cryo-EM. We also discuss correlative light/electron microscopy (CLEM), which integrates fluorescence microscopy and electron microscopy to provide complementary insights. Collectively, these methods offer temporal and spatial insights into investigating the phase separation of protein condensates and filaments, and promote the discovery of unexplored structures and their yet-to-be-characterized biological roles. Full article

Silicene, an atomically thin monolayer allotrope of silicon, had emerged as a prominent topic in condensed matter physics and material science due to its novel properties and promising potential applications. Although challenges exist in fabricating freestanding silicene because of its sensitivity to the conventional environment, its theoretical study continues to develop intensively. This short review highlights the progress made in the ab initio simulations of silicene, such as geometry optimization of silicene and its electrical structure and physical characteristics including optical properties, topological properties and mechanical behavior. The theories and methods used for the theoretical studies of silicene could provide a framework for investigating other one-atom-thick two-dimensional materials with Archimedean lattice structures. Full article

Moving toward sustainable energy in small-scale dairies is an indispensable requirement and a significant challenge in developing countries. This study investigates a solar-powered refrigeration system with heat recovery designed to address the energy challenges faced by small-scale dairy farmers in off-grid areas of developing nations. It presents a novel solar-powered refrigeration system with integrated heat recovery, experimentally optimized to simultaneously deliver heating and cooling while valorizing waste heat and synergistically integrating solar energy to establish a decentralized and energy-autonomous milk preservation system for off-grid applications. The proposed system successfully recovers an average of 55% of the heat rejected by the condenser, thereby delivering more than 1000 W of usable thermal energy necessary for milk pasteurization. The experimental findings showed a coefficient of performance of 4.7, representing a 43% improvement over conventional systems, and achieved a Carnot efficiency of 42%. In addition, the system yields an annual energy savings of 3650 kWh and reduces carbon emissions by 971 kg per year for a 50 L unit. These findings underscore the system’s substantial potential to enhance energy efficiency, promote sustainability, reduce spoilage, improve incomes, mitigate carbon emissions, and enhance local milk preservation capabilities within small-scale dairy operations, minimizing reliance on diesel or firewood, particularly in regions that are distant from access to grid energy. Full article

Background/Objectives: Worldwide, diabetes is a 21st century disease with continuously increasing prevalence. Current medications often have long-term adverse effects, which is why new substances are needed to help combat these disadvantages. Methods: In this respect, the present study develops a series of compounds with potential antidiabetic activity, including synthesis, physicochemical–spectral characterization and in vitro–in silico evaluation. Results: The sulfonamide derivatives were obtained by condensation reactions of para-toluenesulfonamide (p-TSA) with two different isocyanates, directly or after the condensation reaction with urea. The spectroscopic methods, IR, ¹H-NMR, ¹³C-NMR, were used for the structural elucidation of the compounds to confirm the presence of the functional groups responsible for the antihyperglycemic action, namely amide, azomethine and sulfonyl groups. Cytotoxicity screening on NCTC fibroblasts confirmed the excellent safety profile of the most synthesized derivatives across the tested range (100–1500 μg/mL). In contrast, the p-TSA-c-d derivative showed a clear transition from a biocompatible profile at 100 μg/mL to a more cytotoxic phenotype at concentrations exceeding 750–1500 μg/mL. The synthesized derivatives, particularly p-TSA-c-d, exhibited remarkable antidiabetic potential by effectively inhibiting α-amylase and α-glucosidase, with IC₅₀ values as low as 46.54 μM, outperforming the standard reference acarbose. The molecular docking tests revealed different mechanisms for the inhibitory activity exerted by the p-TSA derivatives on the two targeted enzymes. Conclusions: Although these developed compounds can be considered promising antidiabetic agents, studies can be further deepened in the future by performing in vivo tests. Full article

Non-covalent molecular self-assembly serves as a distinctive strategy for enhancing the mechanical performance of lignin-based composite hydrogels. Nevertheless, the self-assembly process can be significantly influenced, leading to alterations in the nanostructure of the hydrogel, because of the diverse conformational reorganizations of lignin in different solvents. In this research, a solvent exchange process was employed to generate a phase-separated structure comprising hydrophobic lignin domains and hydrophilic poly(N,N-dimethylacrylamide) (PDMA) domains through the aggregation of lignin, thereby forming tough lignin/PDMA hydrogels. By adjusting the solvent composition, the hydrogels exhibit distinct nanostructural transformations that are precisely correlated with the changes in Hansen Solubility Parameters (HSPs) of the solvent mixtures. Balanced HSPs facilitates the formation of small-scale lignin domains with high-domain density, which act as crosslinking points for the establishment of a reinforced network. Remarkably, lignin/PDMA hydrogels prepared at a boundary solvation condition unexpectedly induced the formation of large and highly condensed lignin domains, which displayed a radius of gyration (Rg) of 7.7 nm and an inter-domain distance (d-spacing) of 98.1 nm within the hydrogel network. These unique nanostructural features further contribute to its superior mechanical performance, including excellent tensile strength of 3.2 MPa, Young’s modulus of 5.7 MPa, and fracture energy of 41.2 kJ m⁻², which outperforms most reported lignin hydrogels. Additionally, it offers a strong adhesion and rapid drying approach, rendering the hydrogel more suitable for applications as hydrogel coatings. Full article

Background: Enterococcus faecalis is a major cause of complicated urinary tract infections (UTIs), characterized by intrinsic resistance and pronounced biofilm formation. Nitroxoline (NTX), a metal-chelating uroantiseptic, accumulates in urine and exhibits antibiofilm activity. Hydroquinone (HQ), the active urinary metabolite of arbutin-containing herbal preparations, is also excreted into urine and may contribute to antimicrobial activity in situ. This study investigated the antimicrobial and antibiofilm effects of NTX and HQ, individually and in combination, against uropathogenic E. faecalis isolates. Methods: Minimum inhibitory (MIC), bactericidal (MBC), and anti-adhesion (MAC) concentrations were determined using broth microdilution. Interaction was assessed by the checkerboard method and expressed as the fractional inhibitory concentration index (FICI). Biofilm inhibition was quantified by colony-forming unit (CFU) enumeration following exposure to subinhibitory concentrations. Ultrastructural alterations of E. faecalis following exposure to NTX and HQ were examined by transmission electron microscopy (TEM). Results: NTX demonstrated MIC values ranging from 0.002–0.016 mg/mL (MIC50/MIC90: 0.004/0.008 mg/mL), while HQ exhibited MIC values of 0.78–1.56 mg/mL (MIC50/MIC90: 0.78/1.56 mg/mL). Synergistic interactions (FICI ≤ 0.5) were observed in selected isolates, with up to eightfold and sixteenfold reductions in NTX and HQ concentrations, respectively. Additive effects predominated in the remaining isolates without antagonism. The combination achieved 3–5 log₁₀ reductions in adherent bacterial counts compared to untreated controls and up to 4 log₁₀ reductions compared to single-agent exposure. In several strains, complete inhibition of adhesion was observed. TEM analysis revealed marked envelope disruption, cytoplasmic condensation, and structural collapse following combined treatment. Conclusions: Given that both NTX and HQ are active within the urinary environment, their combination may represent a pharmacologically relevant strategy targeting both bacterial growth and early biofilm establishment in enterococcal UTIs. These findings support further in vivo and pharmacokinetic investigations to evaluate the clinical applicability of this combination. Full article

Background: MicroRNAs (miRNAs) are stable, small non-coding RNAs involved in asthma-related pathways and are promising diagnostic biomarkers and therapeutic targets in childhood asthma. Objective: To identify miRNAs differentially expressed in preschool wheezing and childhood asthma, evaluate their association with asthma diagnosis and severity-related phenotypes, and explore their potential translational relevance through exploratory bioinformatic analyses. Methods: A systematic search of Medline, Embase, SCOPUS, PubMed, CINAHL, and Web of Science was conducted for English-language articles published up to March 19, 2025. Eligible human studies reported that miRNAs were differentially expressed in children with wheeze or asthma versus healthy controls (p < 0.05, fold change ≥ 1.5). Bioinformatic analysis identified hub genes, constructed protein–protein interaction networks, and predicted drug–gene interactions. Results: Forty-seven studies met the inclusion criteria, yielding 58 differentially expressed miRNAs (31 up, 27 down). Recurrently reported miRNAs included miR-497, let-7e, miR-98, miR-21, miR-126a, miR-196a2, miR-1, miR-146a-5p, miR-210-3p, miR-145-5p, and miR-200c-3p across blood, nasal swabs, BALF, and exhaled breath condensate. miR-26a showed strong diagnostic performance (sensitivity 83%, specificity 93%; p < 0.002, 95% CI 0.831–0.987). Functional enrichment implicated 56 differentially expressed genes in metabolic and immune processes. Ten hub genes (including TNF, IL5, IL13, TLR4) were linked to 339 potential therapeutic agents; the exploratory network analysis highlighted overlap between predicted miRNA-regulated hub genes and existing asthma-relevant drug targets, including approved biologics. Conclusions: Our review findings suggest that several miRNAs are promising candidate biomarkers for childhood asthma phenotyping and severity assessment; however, their diagnostic utility remains exploratory and requires rigorous external validation and standardisation before clinical application. Full article

Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer’s disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the balance between pathological and physiological condensates. Importantly, amyloid-rich starbursts displayed prion-like infection capabilities toward amyloid-poor condensates. Our findings highlight how the interplay between solution composition and kinetic balances of liquid-liquid phase separation, gelation, and fibrillation shapes the diverse pathological aggregate morphologies characteristic of neurodegenerative diseases. Full article

This work reports the isolation and structural characterization of 1-(2-aminophenyl)-3-(4-pyridyl)-3-hydroxy-1-propanone (1), a β-hydroxyketone intermediate that crystallized unexpectedly during the base-catalyzed aldol condensation of 2-aminoacetophenone with pyridine-4-carbaldehyde, a reaction intended to afford the corresponding pyridyl chalcone (2). The formation of (1) highlights the sensitivity of Claisen–Schmidt reactions to the electronic and steric features of the substrates and to the applied reaction conditions. Single-crystal X-ray diffraction unambiguously confirmed the molecular structure of (1), revealing a hydrogen-bonding network involving the amino, carbonyl, and β-hydroxyl functionalities. These interactions contribute to the solid-state stabilization of the β-hydroxyketone and hinder its dehydration to chalcone (2). The present results provide experimental insight into the mechanistic landscape of aldol condensations and emphasize the relevance of isolable intermediates as structurally defined precursors for further synthetic transformations. Full article

Whether apoptotic cell death occurs in cerebellar Purkinje cells following transient global ischemia remains unclear. Histologic, immunofluorescent and ultramicroscopic methods were used to assess ischemic outcomes in rats. A pilot study using fluorescence labeling [TUNEL-caspase 3-activated peptide (C3AP)-DAPI] revealed key apoptotic characteristics including nuclear TUNEL-positive, nuclear membrane blebs (NMBs), and cytoplasmic C3AP-positive structures, in addition to transport of TUNEL-positive round structures into cytoplasm and projections in ischemic Purkinje cells but not in controls 4 days after ischemia. A formal follow-up study confirmed that 8% of Purkinje cells 4 days following ischemia exhibited TUNEL-positivity and/or NMBs, while Purkinje cells in controls did not. TUNEL-positive Purkinje cells displayed reduced intensity of Calbindin D28K-ifl/MitoTracker (living cell markers) labeling as compared to controls (p < 0.01). Ultramicroscopic evidence of apoptosis included mitochondrial fragmentation and loss in addition to NMBs and cytosolic deposit of nuclear autophagosomes. Interestingly, 71% of the Purkinje cells exhibited autophagy activity after ischemia. Ultramicroscopic characteristics of survival in ischemic Purkinje cells included a centrally located nucleus, no significant chromatin condensation, stable nuclear and intact cytoplasmic membranes, and normal peripheral spacing of the Purkinje cells. In conclusion, four days after transient global ischemia, cerebellar Purkinje cells exhibited both apoptotic and survival characteristics. Further research warrants investigation of the underlying mechanisms. Full article

Agapanthus africanus (L.) Hoffmanns. is a medicinal plant traditionally used in South Africa for its promise as a source of bioactive compounds with anticancer properties. This study aimed to investigate the apoptotic effects of A. africanus fractions on cancer cell lines and to identify the bioactive phytochemical constituents using gas chromatography-mass spectrometry analysis. To test for cytotoxicity, MCF-7, A549, and HeLa cancer cells were treated with crude extract, n-hexane, n-butanol, dichloromethane, and aqueous fractions of A. africanus extracts at different concentrations (0.00–1000 µg/mL). Total apoptosis was quantified using Annexin V/PI staining. The 4′,6-diamidino-2-phenylindole was used to detect nuclear morphological changes and the Caspase-GLO 3/7 assay was employed to check the caspase activation in the cancer cells. Expression of apoptosis-related (caspase-3, bax, bcl-2) genes was evaluated using real time-polymerase chain reaction. The crude extract of A. africanus exhibited dose-dependent cytotoxicity against MCF-7, A549, and HeLa cells, with IC₅₀ values of 130 µg/mL, 380 µg/mL, and <125 µg/mL, respectively. Among the tested fractions, the n-butanol fraction showed cytotoxicity towards MCF-7 cells with an IC₅₀ value of <870 µg/mL. In contrast, n-hexane, dichloromethane and the aqueous fractions exhibited higher IC₅₀ values against cancer cells. Flow cytometry analysis, which was applied to quantify total apoptosis, revealed that the crude extract of A. africanus induced apoptosis by (~60%) compared to the n-butanol fraction, which exhibited a moderate apoptotic effect (~27%). DAPI nuclear staining showed nuclear shrinkage and chromatin condensation in the MCF-7 cell line, whereas in Caspase-GLO 3/7, the crude extract and n-butanol fraction resulted in significant luminescence, indicating activation of caspase-3/7. Caspase-3/7 analysis showed A. africanus treatments produced varying levels of apoptotic activation. The crude extract increased caspase activity by 2.9-fold, while the n-butanol fraction induced a 1.7-fold rise compared with untreated cells. GC-MS chromatograms detected and identified 16 compounds in the fractionated n-butanol and 23 compounds from the crude extract of A. africanus. The major compounds identified from the n-butanol fraction included n-hexadecanoic acid; α-tocopherol and 9,12,15-octadecatrienoic acid, while the GC–MS profile of the crude extract was dominated by 6,10,14-trimethylpentadecan-2-one; 1,3,5-Triphenylcyclohexane and phytol. The study indicates the pro-apoptotic potential of A. africanus, particularly in its crude form, supporting its ethnopharmacological use and suggesting its relevance as a candidate for anticancer drug discovery. Full article

The fluorescence properties of organic molecules are largely determined by molecular architecture, π-conjugation, and electronic substituent effects. In this study, three novel pyrene-chromone Schiff base derivatives were designed and synthesized to investigate substituent-driven modulation of photophysical behavior. The compounds were obtained via condensation of 1-aminopyrene with three different chromone-based aldehydes and fully characterized by FT-IR, ¹H-NMR, and mass spectrometry. The molecular design involves a donor-π-acceptor architecture: pyrene donates electrons, while the chromene moiety accepts them, enabling charge transfer upon excitation. UV-Vis and fluorescence spectroscopy revealed intense absorption in the 430–440 nm range and tunable emission in the 540–565 nm region, corresponding to large Stokes shifts (107–125 nm). Substituent effects significantly influenced optical band gaps and emission intensities, with the nitro-substituted derivative exhibiting a reduced band gap and pronounced fluorescence quenching due to enhanced intramolecular charge transfer. Concentration-dependent absorption studies demonstrated linear Beer–Lambert behavior, indicating the absence of aggregation within the investigated range. These results establish clear structure–property relationships in pyrene-chromene Schiff bases and highlight their potential as promising candidates for optoelectronic and fluorescence-based sensing applications. Full article

Atomic charges play a central role in the analysis of molecular electronic structure and are widely used in the development of computational models. We introduce a simple and computationally efficient extension of Hirshfeld’s 1977 stockholder partitioning method, called scaled Hirshfeld, in which neutral proatom densities are scaled to construct a promolecular density better adapted to the molecular electron density. We present a fixed-point iterative algorithm to compute the proatom scaling coefficients and show that this formulation is equivalent to the information-theoretic additive variational Hirshfeld method with a minimal basis. This equivalence establishes a rigorous mathematical foundation for the scaled Hirshfeld method and ensures size consistency as well as the existence of a unique solution. Numerical results demonstrate that the proposed approach yields charges larger than those obtained with the original Hirshfeld method, while retaining computational efficiency and providing an improved description of molecular dipole moments and electrostatic potentials. Full article

The string-inspired running vacuum model (StRVM) of inflation is based on a Chern–Simons (CS) gravity effective action in which the only four-spacetime-derivative-order term is a gravitational anomalous CS–Pontryagin density coupled to an axion. In this work, we revisit curvature-squared string-inspired effective actions from the point of view of appropriate local field redefinitions, leaving the perturbative string scattering matrices invariant. We require simultaneously unitarity and torsion interpretation of the field strength of the Kalb–Ramond antisymmetric tensor, features characterizing the (3+1)-dimensional StRVM cosmology. Unlike the higher-dimensional case, the above features are possible in the context of (3+1)-dimensional spacetimes, obtained after string compactification. We demonstrate that the unitarity and torsion interpretation requirements lead to a single type of extra four-derivative terms in the effective gravitational action, not discussed in the previous literature on StRVM, which is, however, shown to be subleading by many orders of magnitude compared to the terms of the StRVM framework. Hence, its presence has no practical implications for the relevant inflationary (and, hence, postinflationary) physics of the StRVM. This demonstrates the phenomenological completeness of the StRVM cosmological scenario, which is thus fully embeddable in the UV-complete (quantum gravity-compatible) string theory framework. Full article

This paper introduces a novel cascaded softsign function-based PID (CSoft-PID) controller designed for precise pressure regulation in highly nonlinear shell-and-tube steam condenser systems. For the first time in the literature, the classical PID control structure is enhanced through a cascaded nonlinear transformation using the softsign function, which dynamically adjusts the controller input according to the magnitude of the error. This architecture allows for high sensitivity near the setpoint while gracefully limiting excessive control efforts during larger deviations, thereby improving stability and transient performance. To optimally tune the six parameters of the proposed controller, a new hybrid optimization algorithm, termed hGASO-PS, is proposed. This method synergistically integrates an adaptive gbest-guided atom search optimization (ASO) strategy with the precision of the pattern search (PS) technique, ensuring both effective global exploration and fine-tuned local exploitation. The controller parameters are optimized by minimizing the integral of time-weighted absolute error (ITAE), subject to a step change in the condenser pressure setpoint. Extensive simulations and statistical evaluations demonstrate the superiority of the proposed approach. The hGASO-PS-based CSoft-PID controller achieved the lowest ITAE value of 2.1608, with an average of 2.2746 across 30 runs. It also demonstrated the fastest settling time (12.51 s) and the lowest overshoot (1.98%) among all tested controllers. Comparisons with recent PI, FOPID, and cascaded PI-PDN controllers confirm the consistent outperformance of the proposed method in both transient response and control precision, making it a promising candidate for industrial condenser applications. Full article