Search Results (8,356)

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

With the expansion of global oil and gas resource exploration and development into deep and ultra deep layers, the efficient development of deep carbonate rock fracture cave reservoirs has become the key to ensuring energy security. However, this type of reservoir commonly faces high temperatures, high salinity, and extremely strong heterogeneity, leading to increasingly severe water content spikes caused by dominant water flow channels. Although the existing traditional inorganic plugging agent has good temperature resistance, it has the defects of great brittleness and easy cracking, while the organic polymer gel is prone to degradation failure under high temperature and high salt environments. In order to solve the above problems, a new biochar-enhanced inorganic composite gel system was constructed by using biochar prepared from agricultural and forestry waste pyrolysis as a functional enhancement component. Through rheological testing, high-temperature and high-pressure mechanical experiments, long-term thermal stability evaluation, and dynamic sealing experiments of fractured rock cores, the reinforcement and toughening laws and rheological control mechanisms of biochar on inorganic matrices were systematically studied. Research has found that a biochar content of 0.5 wt% can significantly improve the micro pore structure of the matrix. By utilizing its micro aggregate filling effect and interfacial chemical bonding, the compressive strength of the solidified body can be increased to over 2 MPa, and there is no significant decline in strength after aging at 130 °C for 30 days. More importantly, the unique “adsorption slow-release” mechanism of biochar effectively stabilizes the hydration reaction kinetics at high temperatures, extending the solidification time of the system to 15 h and solving the problem of flash condensation in deep well pumping. This system exhibits excellent shear thinning characteristics and crack sealing ability, and presents a unique “yield reconstruction” toughness sealing feature. This study elucidates the multidimensional strengthening mechanism of biochar in inorganic cementitious materials, providing technical reference for stable oil and water control in deep fractured reservoirs. Full article

Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a natural flavonoid isolated from Epimedium brevicornu Maxim., against C. irritans. In vitro exposure to baohuoside I suppressed theront viability and tomont hatching in a dose- and time-dependent manner, inducing an apoptosis-like death in both stages, characterized by ciliary detachment, mitochondrial disruption, nuclear condensation, and extensive vacuolization, as evidenced by transmission electron microscopy and Annexin V-FITC/PI staining. Further studies demonstrated that baohuoside I elevated the intracellular Ca²⁺ and reactive oxygen species levels in tomonts, indicating Ca²⁺ overload and oxidative stress. Transcriptomic analysis of infected Larimichthys crocea skin revealed that baohuoside I upregulated immune-related genes while downregulating pro-inflammatory genes, concurrently enhancing host serum acid phosphatase activity and mitigating oxidative stress in enzyme activity assays. In vivo trials showed that oral administration of baohuoside I reduced trophont attachment and improved fish survival. It did not exhibit hemolytic activity at concentrations effective against the parasites. Collectively, these findings elucidate a multi-target mechanism of baohuoside I, highlighting its potential as an eco-friendly therapeutic agent for cryptocaryoniasis control in marine aquaculture. Full article

An electrical heating fluidized-bed thermal energy storage (EH-FB-TES) system is proposed for integration with a coal-fired power plant (CFPP) for deep peak shaving (DPS) due to its high energy storage density and extensive heat exchange performance. The primary objective of this study is to evaluate the thermodynamic performance and economic feasibility of the integrated EH-FB-TES system, specifically focusing on identifying the optimal coupling and heat recovery strategies for enhanced deep peak shaving performance. Since EH-FB-TES uses air flow for fluidization in the heating storage process, its coupling with the CFPP differs from other TES technologies, and the associated thermodynamic performance and cost are thereby analyzed. The results show that, in EH-FB-TES, the heat release efficiency is predominantly constrained by thermal losses. To increase the energy utilization efficiency, a two-stage heat recovery strategy is proposed to release the stored energy in the integration. The first stage is to heat up the feedwater extracted from the deaerator and the second one is to heat up the condensate water. The analyses also show that the selection of reinjection positions for the heated medium from EH-FB-TES greatly influences the system performance. Returning the stored thermal energy to heat up feedwater can effectively increase the output of the unit, while directly generating steam can be beneficial for coal saving. The integrated system achieves a maximum equivalent round-trip efficiency of 32.9% under 20 MW/800 °C conditions. An economic analysis reveals that, compared with other energy storage methods, EH-FB-TES can realize a relatively high energy storage density with a rather low cost. Under the present DPS compensation policy, for a 315 MW subcritical CFPP integrated with a 50 MW EH-FB-TES system, when heat storage is 8 h, heat release is 4 h per day, and the plant operates 100 days per year, the estimated static and dynamic payback periods are 3.06 years and 3.67 years, respectively. The integration of CFPP with EH-FB-TES could be promising for meeting DSP requirements. Full article

This study examines the influence of SO₂ and its hydrate H₂SO₃ on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO₂ and H₂SO₃ readily condense with aldehyde and alcohol functional groups to form bisulfite analogs of formose proto-metabolites under modeled conditions. The bisulfite functional group can provide intramolecular catalytic enhancement in specific isomers towards aldol additions and the retroaldol step that regenerates two equivalents of glycolaldehyde from tetrose. The bisulfite moiety reduces the favorability of the parasitic Cannizzaro side-reaction both thermodynamically and kinetically, thus potentially furnishing more throughput towards forming sugars. As a prebiotic analog to phosphate, we find that bisulfite slightly stabilizes ribose over its C₅ aldose diastereomers thermodynamically, although the effect is modest and may be influenced by solution dynamics. Full article

This study investigates the applicability of alternative low-global warming potential (GWP) refrigerant blends in water-source heat pump systems. Binary and ternary refrigerant mixtures were generated using REFPROP 10 to identify suitable candidates. Among 379 novel blends, 18 mixtures with glide temperatures below 10 °C, high critical temperatures, and GWP values lower than 750 were selected for analysis. Thermodynamic analyses were conducted for the selected refrigerants at target water outlet temperatures ranging from 35 to 75 °C, with a heat source temperature of 15 °C and an evaporation temperature of 5 °C. In addition, compressor discharge temperature, volumetric heating capacity, and coefficient of performance (COP) were evaluated. Among the refrigerants, MX1 was recommended for condenser temperatures of 40–80 °C in large-scale heat pump and district heating applications. For refrigerants with GWP values below 150, MX7 exhibited the highest COP and second-law efficiency (η_II) and is therefore suitable for small-capacity systems. In the GWP range of 150–750, MX16 demonstrated the highest COP and η_II values over the entire temperature range. Overall, MX7 achieved the highest COP and η_II among all refrigerants considered, while MX4 emerged as the most favorable mixture in terms of low GWP (below 150) and thermophysical performance. Full article