Search Results (390)

Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan^® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article

In this paper, cultivable actinobacteria were isolated, cultured, and identified from the heavily algal-bloomed waters of Taihu Lake using 16S rRNA gene sequencing. Among the isolates, a single strain exhibiting vigorous cyanocidal activity against Microcystis aeruginosa FACHB-905 was selected for further investigation. The cyanocidal efficacy and underlying mechanisms of this strain, designated TH05, were assessed through using chlorophyll content, cyanobacterial inhibition rate, and cyanobacterial cell morphology measurements. In addition, oxidative stress responses, expression of key functional genes in FACHB-905, and variations in microcystin concentrations were comprehensively evaluated. Cyanobacterial blooms caused by Microcystis aeruginosa pose serious ecological and public health threats due to the release of microcystins (MCs). In this study, we evaluated the cyanocidal activity and mechanism of a novel actinomycete strain, Streptomyces sp. TH05. Optimization experiments revealed that a light–dark cycle of 12 h/12 h, temperature of 25 °C, and pH 7 significantly enhanced cyanocidal efficacy. Under these conditions, TH05 achieved an 84.31% inhibition rate after seven days of co-cultivation with M. aeruginosa. Scanning electron microscopy revealed two distinct cyanocidal modes: direct physical attachment of TH05 mycelia to cyanobacterial cells, causing cell wall disruption, and indirect membrane damage via extracellular bioactive compounds. Biochemical analyses showed increased levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) during the first five days, peaking at 2.47-, 2.12-, and 1.91-fold higher than control levels, respectively, indicating elevated oxidative stress. Gene expression analysis using elf-p as a reference showed that TH05 modulated key genes associated with photosynthesis (PsaB, PstD1, PstD2, RbcL), DNA repair and stress response (RecA, FtsH), and microcystin biosynthesis (McyA, McyD). All genes were upregulated except for RbcL, which was downregulated. In parallel, microcystin content peaked at 32.25 ng/L on day 1 and decreased to 16.16 ng/L by day 9, which was significantly lower than that of the control group on day 9 (29.03 ng/L). These findings suggest that strain TH05 exhibits potent and multifaceted cyanocidal activity, underscoring its potential for application in the biological control of cyanobacterial blooms. Full article

Exposure to extremely low-frequency magnetic fields (ELF-MF) can induce biological alterations in human cells, including peripheral blood mononuclear cells (PBMCs). However, the molecular mechanisms and key regulatory factors underlying this cellular response remain largely unknown. In this study, we analyzed the proteomic profiles of PBMCs isolated from three human subjects. PBMCs were exposed to 50 Hz, 1 mT of ELF-MF for 24 h and compared to unexposed PBMCs from the same individuals. ELF-MF exposure altered the expression levels of several PBMC proteins without affecting cell proliferation, cell viability, or cell cycle progression. A total of 51 proteins were upregulated, 36 of which were intercorrelated and associated with the Cellular Metabolic Process (GO:0044237) and Metabolic Process (GO:0008152). Among them, solute carrier family 25 member 4 (SLC25A4), which catalyzes the exchange of cytoplasmic ADP for mitochondrial ATP across the inner mitochondrial membrane, was consistently upregulated in all ELF-MF–exposed samples. Additionally, 67 proteins were downregulated, many of which are linked to T cell costimulation (GO:0031295), Cell activation (GO:0001775), and Immune system processes (GO:0002376) included ASPSCR1, PCYT1A, PCYT2, QRAS, and REPS1. In conclusion, ELF-MF exposure induces metabolic reprogramming in human PBMCs, characterized by the upregulation of mitochondrial proteins and downregulation of immune-activation-related proteins, without compromising cell viability or proliferation. Full article

The regioselectivity and the molecular mechanism of the Diels–Alder reactions between N-(2,2,2-trichloroethylidene)carboxamides and dicyclohexylcarbodiimide were explored based on the ωB97xd/6-311G(d) (PCM) calculations. It was found that the reaction course is determined by polar local interactions. It is interesting that the most favored reaction channel is realized not via classical single-step Diels–Alder mechanism, but according to the stepwise scheme with the intervention of the zwitterionic intermediate. The details of the electron density redistribution along the reaction coordinate were explained using the ELF technique. Full article

Germanium/tin-containing silicon oxide [SiO–(GeO/SnO)] nanoclusters have been designed with different Si/Ge/Sn particles and characterized as electrodes for magnesium-ion batteries (MIBs) due to forming MgBe [SiO–GeO], MgBe [SiO–SnO], MgCa [SiO–GeO], and MgCa [SiO–SnO] complexes. In this work, alkaline earth metals of magnesium (Mg), beryllium (Be), and calcium (Ca) have been studied in hybrid Mg-, Be-, and Ca-ion batteries. An expanded investigation on H capture by MgBe [SiO–(GeO/SnO)] or MgCa [SiO–(GeO/SnO)] complexes was probed using computational approaches due to density state analysis of charge density differences (CDD), total density of states (TDOS), and electron localization function (ELF) for hydrogenated hybrid clusters of MgBe [SiO–GeO], MgBe [SiO–SnO], MgCa [SiO–GeO], and MgCa [SiO–SnO]. Replacing Si by Ge/Sn content can increase battery capacity through MgBe [SiO–GeO], MgBe [SiO–SnO], MgCa [SiO–GeO], and MgCa [SiO–SnO] nanoclusters for hydrogen adsorption processes and could improve the rate performances by enhancing electrical conductivity. A small portion of Mg, Be, or Ca entering the Si–Ge or Si–Sn layer to replace the alkaline earth metal sites could improve the structural stability of the electrode material at high multiplicity, thereby improving the capacity retention rate. In fact, the MgBe [SiO–GeO] remarks a small enhancement in charge transfer before and after hydrogen adsorption, confirming the good structural stability. In addition, [SiO–(GeO/SnO)] anode material could augment the capacity owing to higher surface capacitive impacts. Full article

Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply. Full article

Cancer has a threatening impact on human health, and it is one of the primary causes of fatalities worldwide. Different conventional treatments have been employed to treat cancer, but their non-specific nature reduces their therapeutic efficacy. This study employs a C₅N₂-based targeted drug carrier to study the delivery mechanism of anticancer drugs, particularly cisplatin, carmustine, and mechlorethamine, using density functional theory (DFT). The geometries of the drugs, the C₅N₂ substrate, and the drug@C₅N₂ complexes were optimized at the PBE0-D3BJ/def2SVP level of theory. Interaction energy was computed for the complexes which follow the trend, i.e., cisplatin@C₅N₂ (−27.60 kcal mol⁻¹) > carmustine@C₅N₂ (−19.69 kcal mol⁻¹) > mechlorethamine@C₅N₂ (−17.79 kcal mol⁻¹). The non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses confirmed the presence of van der Waals forces between the carmustine@C₅N₂ and mechlorethamine@C₅N₂ complexes, while weak hydrogen bonding has also been observed between the cisplatin@C₅N₂ complex. Electron localization function (ELF) analysis was performed to analyze the degree of delocalization of electrons within the complexes. The electronic properties of the analytes and the C₅N₂ substrate confirmed the enhanced reactivity of the complexes and illustrated electron density shift between the drugs and the C₅N₂ sheet. Recovery time was determined to assess the biocompatibility and the desorption behavior of the drugs. Moreover, negative solvation energies and increased dipole moments in a solvent phase manifested enhanced solubility and easy circulation of the drugs in biological media. Subsequently, this study illustrates that cisplatin@C₅N₂, carmustine@C₅N₂, and mechlorethamine@C₅N₂ complexes can be utilized as efficient drug delivery systems. Full article

This study presents a theoretical investigation of the electronic properties of mono- and pentasubstituted cyclopentadiene analogs and variously substituted conjugated nitroalkenes bearing electron-donating and electron-withdrawing groups. Conceptual Density Functional Theory (CDFT) and Electron Localization Function (ELF) analyses were employed to characterize the global and local reactivity indices of the reactants. The obtained data provided insights into the nucleophilic and electrophilic nature of the investigated systems, allowing for the prediction of their reactivity patterns in Diels–Alder reactions. A reactivity model for conjugated alkenes toward cyclopentadienes was developed based on correlation analysis using Hammett substituent constants. This approach enabled the prediction of reaction polarity in (4+2) cycloaddition processes, providing insight into how the electronic effects of substituents influence the reaction course. These findings contribute to a deeper understanding of structure–reactivity relationships in Diels–Alder processes. Full article

The mechanism of the DA cycloaddition reaction between the pyridine adduct of borabenzene and acetylene has been investigated using topological analysis of the electron localization function (ELF) and catastrophe theory (bonding evolution theory, BET). The study focuses on the differences in the electronic structures of C-C and C-B bonds during their formation. Additionally, the influence of electron density functionals with different constructions (B3LYP, CAM-B3LYP, B2PLYP, M06, M062X, and M052X) on the BET results was examined. The reaction proceeds through ten distinct phases. The B-C bond forms first, followed by the C-C bond. Significant differences were observed in the behavior of the non-bonding basins V(C) and V(B) compared to the V(C), V(C) basins, which precede the formation of the bonding basins V(B,C) and V(C,C). The use of different functionals results in quantitative variations in the lengths and positions of the reaction phases—for example, relative to the transition state structure. A possible qualitative influence on the overall picture of the reaction mechanism is suggested by the results obtained using the CAM-B3LYP and B2PLYP functionals, particularly in phases VI and VII. Full article

Using Schumann resonance (SR) records from the Antarctic, we evaluate the impact of the solar activity on the global ionosphere over the period from 2002 to 2024. The updated vertical profile of the middle atmosphere conductivity is applied. The pivoted upper part of profiles above the knee altitude is adjusted to represent different levels of solar activity. The electric (lower) h_C and the magnetic (upper) h_L characteristic heights, the propagation constant ν(f) of the extremely low frequency (ELF) radio waves, and the basic resonance frequency f₁ are computed for the profiles corresponding to the solar maximum, moderate, and minimum activity conditions by using the full-wave solution in the form of the Riccati differential equation. Model data are compared with experimental observations at the Ukrainian Antarctic Station of “Akademik Vernadsky” (geographic coordinates: 65.25° S and 64.25° W). The following results are discussed: (i) Solar activity modifies the upper characteristic height h_L of the ionosphere by ±1 km over the 11-year cycle; (ii) Equations were obtained linking the current level of solar activity with the basic SR frequency, with the magnetic characteristic height, and with the ELF propagation constant; (iii) Based on SR monitoring within two complete solar cycles, a practical rule is proposed: an increase in the index of solar activity I_10.7 by ~150 units raises the first SR frequency by ~0.1 Hz and elevates the magnetic characteristic height by ~2.5 km. Full article

This study employs Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations to investigate interactions between water molecules and Poly(N-isopropylacrylamide) (PNIPAM). DFT reveals preferential water binding sites, with enhanced binding energy observed in the linker zone. Quantum Theory of Atoms in Molecules (QTAIM) and electron localization function (ELF) analyses highlight the roles of hydrogen bonding and steric hindrance. MD simulations unveil temperature-dependent hydration dynamics, with structural transitions marked by changes in the radius of gyration (Rg) and the radial distribution function (RDF), aligning with DFT findings. Our work goes beyond prior studies by combining a DFT, QTAIM and MD simulations approach across different PNIPAM monomer-to-30mer structures. It introduces a systematic quantification of pseudo-saturation thresholds and explores water clustering dynamics with structural specificity, which have not been previously reported in the literature. These novel insights establish a more complete molecular-level picture of PNIPAM hydration behavior and temperature responsiveness, emphasizing the importance of amide hydrogen and carbonyl oxygen sites in hydrogen bonding, which weakens above the lower critical solution temperature (LCST), resulting in increased hydrophobicity and paving the way for understanding water sorption mechanisms, offering guidance for future applications such as dehumidification and atmospheric water harvesting. Full article

Three diaryliodonium dicyanoargentates(I), [MesIAr][Ag(CN)₂] (Ar = Ph 1, Mes 2, 4-MeC₆H₄ 3; Mes = 2,4,6-Me₃C₆H₂), were prepared by anion metathesis. The X-ray structural analyses for these crystals revealed C–I^III∙∙∙N≡C halogen bonds (abbreviated as XB) between I atoms of diaryliodonium cations and N atoms of cyano groups, which provide different supramolecular organization. The noncovalent nature of these interactions was studied by density functional theory (DFT) calculations and topological analysis of the electron density distribution in the framework of the quantum theory of atoms in molecules (QTAIM) at the PBE-D3/jorge-DZP-DKH level of theory both in gas phase and crystal models. The philicities of partners in these contacts were confirmed by electron localization function (ELF) projections, electron density/electrostatic potential (ED/ESP) profiles, and Hirshfeld surfaces analysis. An analysis of the available crystallographic data from the literature allows us to find other examples of σ-hole interactions including the dicyanoargentate(I) anion, and the C–X∙∙∙N≡C (X = Br, I, Te) bonding were also confirmed theoretically. Full article

Objective: The objective of this study was to calculate the epidemiological impact of metabolic dysfunction associated with fatty liver disease (MAFLD) and hepatic fibrosis in primary care (PC). Secondarily, we assessed the correlation between serological markers (FIB-4, ELF test), abdominal ultrasound, and transient elastography in the early detection of MAFLD. Methods: An observational prospective study was designed to determine the prevalence of MAFLD and to assess the correlation between complementary tests. Patients were recruited from five health centres. Eligible participants were adults aged between 18 and 70 years with at least one metabolic risk factor, including being overweight (BMI 25–29.9 kg/m²) or obese (BMI > 30 kg/m²), or diagnosed with type 2 diabetes mellitus (T2DM), dyslipidemia, or metabolic syndrome. The prevalence of MAFLD was calculated. Correlations between diagnostic tests were evaluated using Pearson’s correlation coefficient. Results: A total of 98 patients was included. Using CAP (controlled attenuation parameter) measurements, the prevalence of MAFLD was found to be 67.7%, and the prevalence of hepatic fibrosis was 6.5%. The correlation between conventional ultrasound and CAP from FibroScan^® for the diagnosis of MAFLD was low and not statistically significant (0.160 [95% CI: −0.100; 0.400], p = 0.226). In contrast, the diagnosis of hepatic fibrosis using FibroScan^® in PC showed a high correlation with diagnoses performed in gastroenterology department (0.942 [95% CI: 0.844; 0.979], p < 0.001). The correlation with biochemical markers was low and not statistically significant for both FIB-4 (0.125 [95% CI: −0.129; 0.363], p = 0.334) and the ELF test (0.159 [95% CI: −0.111; 0.407], p = 0.246). Conclusions: Two out of three patients with metabolic risk factors were diagnosed with MAFLD, while hepatic fibrosis diagnoses were uncommon. These results reinforce the validity of using FibroScan^® in PC. Full article

Background: The incidence of external lymphatic fistula (ELF) represents a relatively rare complication after surgery for colorectal cancer, especially in Western countries. However, the rate of this complication is progressively increasing following the introduction of complete mesocolic excision and central vascular ligation with consequent extensive lymphadenectomy. There are no guidelines for the management of ELF, with therapeutic options varying from conservative procedures to more invasive surgeries. The aim of this study was to retrospectively quantify the rate of ELF after surgery for colorectal cancer, to describe its management, and to evaluate its clinical impact on early postoperative outcomes in a tertiary referral European centre. Methods: Data on all patients who underwent surgery for colorectal cancer at our institution between July 2022 and December 2024 were entered into a database. Preoperative, perioperative, and early (within 30 days) postoperative data were recorded. Results: A total of 279 patients underwent elective surgery for colorectal cancer (205 colon and 74 rectum). No postoperative deaths occurred within 30 days after surgery, and the rates of overall and major (grade ≥ 3) postoperative morbidity were 34.7% and 7.1%, respectively. The anastomotic leakage and reoperation rates were 2.8% and 5.3%, respectively. ELFs occurred in 15 patients (5.3%). In all patients, conservative treatment (based on fasting, total parenteral nutrition (TPN), and a prolonged medium-chain triglyceride (MCT) diet) was administered successfully. A recurrent ELF (after the first oral feeding resumption) occurred in four (26.6%) patients, but all were successfully treated with a conservative approach. The occurrence of an ELF prolonged the postoperative length of stay which was 12 days, a length higher than that recorded in patients without ELF. Conclusions: The occurrence of an ELF was found to be a relatively frequent complication after surgery for colorectal cancer and appears to negatively influence only the postoperative length of stay. Conservative management appeared to be a successful treatment. Full article

Background: Achieving pharmacokinetic/pharmacodynamic (PK/PD) targets is critical for improving treatment success, particularly in critically ill patients. This study investigates the role of inflammatory biomarkers and their influence on the PK/PD characteristics of polymyxin B (PMB) in patients with extensively drug-resistant Gram-negative (XDR-GN) bacterial nosocomial pneumonia. Methods: Serial blood and/or bronchoalveolar lavage fluid (BALF) samples were collected at specified time points and analyzed for PMB and/or inflammatory biomarkers, including IL-6 and IL-10. Clinical data were also recorded, and their correlations with PK parameters were further analyzed. Results: Among the 27 enrolled patients, 22 (81.5%) achieved treatment success. The pharmacokinetic parameters of PMB included a maximum plasma concentration (C_max) of 8.3 µg/mL, clearance (CL) of 1.55 L/h, volume of distribution (Vd) of 30.44 L, half-life (t_1/2) of 19.56 h, steady-state area under the plasma concentration–time curve from time 0 to 24 h (AUC_ss,0–24h) of 110.08 h·µg/mL, and a plasma protein-binding ratio of 85.53%. The AUC_ss,0–24h metric was identified as a robust predictor of clinical efficacy, with an optimal cutoff value of 77.27 h·µg/mL. Notably, 48.15% of patients achieved the target AUC_ss,0–24h range of 50–100 h·µg/mL, with 76.95% of these patients attaining treatment success. Another 48.15% of patients exceeded this target, and 92.31% of this subgroup achieved treatment success. PMB demonstrated limited pulmonary penetration, with an epithelial lining fluid (ELF)/plasma ratio of 15.69% [16.86, 18.15]. Furthermore, TNF-α and the IL-6/IL-10 ratio were significantly correlated with PMB PK parameters. Conclusions: Our and others’ studies suggest heterogeneity of PMB PK parameters in critically ill patients. The majority of critically ill patients achieved or surpassed the recommended PK/PD targets and attained treatment success through intravenous administration of PMB at a simplified fixed dose. However, PMB did not achieve satisfactory pulmonary concentrations, suggesting that its efficacy may involve alternative mechanisms. The modulation of inflammatory responses may play a pivotal role in the treatment of severe infections, highlighting the potential for biomarker-guided therapeutic strategies. Full article