Introduction: Obesity is a complex disorder characterised by inflammatory and metabolic response system disorders. There is increasing evidence that the gut microbiota influences host physiology by producing bioactive metabolites. The metabolic byproducts of probiotic fermentation, such as branched-chain amino acids and short-chain fatty acids, affect immune regulation. However, we do not know how these metabolites systemically act in host inflammatory signalling. Methods: A meta-analysis was performed to characterise interactions between microbial metabolites and host inflammatory markers related to obesity. The Human Metabolome Database (HMDB) was used to retrieve metabolites, and the STRING database was used to identify host protein targets. Analysis using KEGG and Reactome revealed important involvement in sphingolipid metabolism, antimicrobial peptide activity, and BCAA degradation. Results: With network analysis, cytokine signalling, insulin regulation, and adipocytokine pathways were disturbed. Conclusion: This revealed the immunometabolic importance of the gut microbiota and suggested that probiotic metabolites could be potential therapeutic targets for obesity-induced inflammation.
BACKGROUND:With rapid global population ageing, older women bear a disproportionate burden of cognitive impairment, depression, and anxiety. Reproductive history, a unique and irreversible life course factor, may influence late-life cognitive and mental health. METHODS:We included 4,173 women aged ≥65 years from the 2017-2018 China Longitudinal Healthy Longevity Survey. Standard scales assessed cognition and mood, followed by regression, network, and two-sample MR analyses. RESULTS:After adjustment, having more than four births was associated with a lower risk of cognitive impairment (OR = 0.66, 95% CI: 0.48-0.91). Network analysis identified restlessness and uncontrollable worry as central symptoms, with language and attention as key bridge nodes. MR analyses linked higher parity to poorer cognition and later first birth to better cognition and lower depression risk. CONCLUSION:Reproductive history is linked to late-life cognitive and emotional health through sociocultural and biological mechanisms, highlighting the importance of population-specific precision health strategies.
Atoms emit energy in the form of ionising radiation, which can be transmitted as particles (alpha, beta, or neutrons) or electromagnetic waves (gamma or X-rays). Ionising radiation has been shown in cellular and animal models to be a potential toxicity risk factor. The purpose of this research was to examine the probable protective effect of cinnamaldehyde nano-emulsion against gamma-irradiation-induced nephrotoxicity in albino rats. Forty-eight rats were separated into eight groups (6 rats/group) as follow; the control group I, the first treated group II (rats were received 40 mg/kg B.W. cinnamaldehyde), second treated group III (rats were received 40 mg/kg B.W cinnamaldehyde nano-emulsion), irradiated group IV (rats were exposed to 8 Gy single dose gamma-radiation), first treated irradiated group V (rats were received 40 mg/kg B.W. cinnamaldehyde for 7 days, and at day 7, they were exposed to 8 Gy single dose gamma-radiation), the other treated irradiated groups VI, VII, and VIII (rats were received 40, 20, and 10 mg/kg B.W. cinnamaldehyde nano-emulsion respectively, for 7 days and on day 7, they were exposed to 8 Gy single dose gamma-radiation). The results demonstrated that the cinnamaldehyde and cinnamaldehyde nano-emulsion administration to animals before irradiation significantly amended the alterations that happened in the renal functions compared with irradiated group. Similarly, the alterations in renal tissue malondialdehyde, total antioxidant capacity, tumour necrosis factor-α, interleukin-1β levels, and nuclear factor erythroid 2-related factor 2, and haem oxygenase-1 relative genes expressions were markedly ameliorated compared with the irradiated group. The irradiation group's histological results displayed characteristic renal lesions, but the other irradiated treated groups' renal tissues had relatively well-preserved architecture. Cinnamaldehyde and cinnamaldehyde nano-emulsion act as a potent free radicals' scavenger in the kidney to prevent or improve the toxic consequences of gamma-irradiation as revealed by biochemical and histopathological variations, and may provide considerable protection against radiation-induced inflammatory damage, particularly in the nano-emulsion form.
Type 2 diabetes mellitus (T2DM) affects over 415 million individuals globally, with excessive hepatic glucose production representing a primary contributor to hyperglycaemia. Fructose-1,6-bisphosphatase (FBP1), a rate-limiting gluconeogenic enzyme, has emerged as a promising therapeutic target. This review examines FBP1's molecular mechanisms, including its tetrameric structure and allosteric regulation by AMP. FBP1 dysregulation in diabetes involves transcriptional control by FOXO1, CREB, PGC-1α, and epigenetic modifications. Drug discovery efforts have yielded diverse inhibitor classes, including AMP-competitive inhibitors, covalent modulators targeting cysteines C128/C179, and natural products. Leading compounds demonstrate exceptional potency (IC50 0.029 μM) with favourable bioavailability and efficacy in preclinical models. Structure-based design and AI-driven approaches have accelerated optimisation. Clinical translation of FBP1 inhibitors represents a paradigm-shifting opportunity, potentially providing the first medication class specifically targeting hepatic gluconeogenesis for T2DM treatment.
Blood glucose metabolism is a key process for maintaining normal physiological functions of the human body. The maintenance of its homeostasis relies on complex hormone regulation and the synergistic effect of tissues and organs. However, when insulin resistance occurs in skeletal muscles, insulin signalling is impaired, and glucose uptake decreases, leading to elevated blood sugar levels. This study investigates the SARS-CoV-2 spike protein's effect on insulin resistance in type 2 diabetes (T2DM) skeletal muscle in a specific demographic. In the cell experiment, we used human C2C12 skeletal muscle cells and co-cultured them with the spike protein to observe the effects of the spike protein on the proliferation, apoptosis, and glucose uptake. The research results show that the spike protein may reduce the expression and transport of GLUT4 by inhibiting the PI3K/AKT/mTOR signalling pathway, thereby decreasing glucose uptake, intensifying insulin resistance in skeletal muscle, and affecting blood glucose metabolism.
OBJECTIVE:This study investigated the clinical significance of serum miR-339-5p in MASLD and explored its molecular mechanisms in hepatic steatosis and inflammation. METHODS:87 MASLD patients (Np-MASLD, n = 51; MASH-F, n = 36) were enrolled. Serum miR-339-5p was quantified and correlated with clinical indices. In vitro studies used FFA-treated HepG2 cells to assess miR-339-5p and SORT1 effects on lipid accumulation, inflammation. RESULTS:Serum miR-339-5p was significantly elevated in MASLD, correlating positively with disease severity, and served as an independent risk factor for MASH-F progression. In HepG2 cells, miR-339-5p overexpression exacerbated FFA-induced lipid accumulation and IL-6/TNF-α secretion, whereas its inhibition exerted protective effects. SORT1 was validated as a direct target of miR-339-5p and was downregulated in MASLD. miR-339-5p suppressed AMPK phosphorylation and promoted NF-κB activation by targeting SORT1. CONCLUSION:Elevated miR-339-5p promotes hepatocyte lipid accumulation and inflammation in MASLD, potentially by targeting SORT1.
Context: Diabetic kidney disease (DKD) presents substantial challenges in early detection and clinical monitoring. Mitochondrial dysfunction plays a pivotal role in DKD pathogenesis, and mitochondrial DNA copy number (mtDNA-CN) reflects this dysfunction. Objective: To evaluate the translational potential of mtDNA-CN as a biomarker for DKD, focusing on its diagnostic, prognostic, and monitoring utility across biological specimens, and examine the critical challenges of its clinical translation. Materials and Methods: We systematically synthesize evidence from cellular experiments, animal models, and clinical studies that assess mtDNA-CN alterations in DKD, with a comparative analysis of specimen types and methodologies. Results: Studies demonstrated that mtDNA-CN in blood and urine are correlated with the onset and progression of DKD. Rigorous standardization must be implemented across specimen collection, pre-analytical processing, analytical testing, detection and data reporting. Conclusion: MtDNA-CN is a promising and measurable biomarker for DKD. Combined with conventional markers, it could enhance clinical utility.
Background: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition associated with high morbidity and mortality, characterized by severe inflammation, oxidative stress, impaired gas exchange, and progressive lung injury. Disruption of cellular redox homeostasis plays a central role in ARDS pathogenesis, making redox-regulatory mechanisms attractive therapeutic targets. Methods: This review evaluates experimental evidence on protein-mediated regulation of oxidative stress pathways in ARDS, focusing on proteins involved in antioxidant defense, reactive oxygen species (ROS) generation, mitochondrial signaling, and maintenance of cellular redox homeostasis. Results: Current evidence indicates that key regulatory proteins modulate oxidative stress by activating endogenous antioxidant defense systems, regulating ROS production, and influencing mitochondrial signaling pathways. These mechanisms reduce oxidative damage and pulmonary inflammation while preserving cellular redox balance. Experimental studies further demonstrate that modulation of specific protein regulators enhances cellular resilience under hypoxic and inflammatory conditions characteristic of ARDS. Conclusions: Protein-mediated regulation of redox signaling represents a promising therapeutic strategy for ARDS. Targeting redox-regulatory proteins may attenuate oxidative stress, reduce lung inflammation, and improve cellular survival, supporting their potential as novel therapeutic targets. Further preclinical and clinical studies are needed to validate these findings and facilitate their translation into clinical practice.
Background: Globally, preterm birth continues to be a major contributor to neonatal morbidity and mortality. Developing early diagnostics and focused interventions requires an understanding of the molecular and microbiome factors causing preterm birth and also the identification of biomarkers. Methods: We integrated gut microbiome and DNA methylation data to identify biomarkers of preterm birth. Analysis of GSE120458 revealed 1,609 differentially methylated regions involved in immune, hormonal, and neurodevelopmental pathways. Microbiome profiling identified five altered genera: Faecalibacterium prausnitzii, Streptococcus, Blautia faecis, Gemella, and Agathobacter. Taxon Set Enrichment Analysis revealed that these genera were found to be associated with systemic diseases like diabetes, obesity, and inflammatory bowel disease. Results: We identified 1,649 genes targeted by 33 microbial metabolites, with 17 overlapping methylated genes indicating microbiome-epigenome interactions. These genes were linked to neuroimmune and synaptic pathways. Conclusion: Hub genes may serve as biomarkers for early intervention. Overall, the results connect microbial metabolism with epigenetic regulation in preterm birth.
Diabetes mellitus is associated with neurochemical and lung imbalances. This study investigates the therapeutic potential of exosome (Exo) treatment in ameliorating systemic complications in a rat model of type 2 diabetes. Eighteen male rats were divided into three groups: Control, Diabetic, and Diabetic + Exosome-treated. After the intervention period, serum, brain, and lung tissues were analysed. In serum, diabetes induced hyperglycaemia and dyslipidaemia, all of which were significantly improved by Exo (p < 0.001). Diabetic rats exhibited significant elevations in brain malondialdehyde, mTOR, and GSK3β, along with reduced glutathione, serotonin, and dopamine (all p < 0.001 vs. Control). Exo treatment reversed these changes (p < 0.001 vs. Diabetic). In lung tissue, diabetes increased MDA, TRPM2, and NLRP3 while suppressed superoxide dismutase; Exo treatment ameliorated these issues (p < 0.001). Exosomes exert potent antioxidant and anti-inflammatory in type 2 diabetic rats in the brain and lungs.
We propose an analytical model and perform numerical simulations to study the time distribution of the characteristic muonic oxygen X-ray emission following muon transfer from muonic hydrogen to oxygen in a H2 + O2 gas mixture. The model accounts for all fundamental processes that alter the kinetic energy and spin distribution of muonic hydrogen atoms. The impact of the uncertainties in various experimental parameters on the precision of the computed results is studied in detail by means of the Monte Carlo method. Specifically, we observe the presence of a minimum in the time dependence of the relative standard deviation of X-ray emission for realistic parameter combinations, which can serve as a benchmark for comparing experiments and numerical simulations. Verification against available experimental data reveals the potential of this approach for both description and parameter optimization in the planning and analysis of muonic experiments
We investigate theoretically the 75 keV proton-impact ionization of atomic helium. The convoluted quasi-Sturmian approach is extended to treat, on an equal footing, both the direct mechanism and the electron capture to the continuum. This is achieved by proposing an ansatz of the Green's function of the three-body Coulomb system (e-,He+,p+) that is compatible with the well-known 3C correlated continuum wave function. The model that stems from this approximation, named 3C, is tested numerically using parabolic Sturmian expansions. Calculations of fully differential cross sections are presented for different regimes of energy losses, namely for ejected electron energies below, nearly equal to, and above the cusp energy. Our results are compared with recent experimental measurements and other theoretical calculations. The proposed 3C model yields very encouraging results and paves the way towards a more advanced Lippmann-Schwinger approach based on the 3C model.
We present fully relativistic calculations of integral cross sections and swarm transport properties for positron-radon scattering over a wide energy range (0-1000 eV) and reduced electric field range (0.01-1000 Td). Elastic (total, momentum-transfer and viscosity-transfer), discrete excitation, direct annihilation, positronium formation and positron-impact ionization cross sections are obtained using a complex relativistic optical potential method. Owing to the large atomic number of radon and the absence of experimental scattering data, a consistent relativistic treatment is essential. The present work provides the first fully relativistic, internally consistent cross-section dataset for positron swarms in radon gas. Using a multi-term solution of Boltzmann's equation, steady-state transport coefficients are calculated and found to be strongly influenced by energy-dependent reactive loss, particularly positronium formation. Significant divergence between bulk and flux transport coefficients is observed, including non-monotonic bulk drift velocities and pronounced suppression of longitudinal bulk diffusion at intermediate fields (0.3-1000 Td). Time-dependent field-free calculations further quantify thermalization and annihilation dynamics through the evolution of the mean energy and < Zeff >(t). These results provide a robust theoretical foundation for modelling positron transport and annihilation in radon and other heavy noble gases where relativistic and reactive effects are crucial.
A developed method, based on the stationary second-order Rayleigh-Schr & ouml;dinger many-body perturbation theory in an irreducible tensorial form, allows us to determine the most important core-valence, core, core-core, and valence-valence correlations for any atom or ion with an arbitrary number of valence and core electrons. This paper presents the Feynman diagrams that describe these correlations. Additionally, it provides the rules for obtaining algebraic expressions in an irreducible tensorial form for any Feynman diagram coming from second-order many-body perturbation theory. Whereas some types of the valence-valence and core-valence correlations are described by the three-particle Feynman diagrams, additional developments to calculate the spin-angular parts of these diagrams have been made to the program library librang of the Grasp2018 As an example of the application of the developed method, the atomic calculations of the energy level structure and transition data for Ar II are presented.
Laser-induced breakdown in water-rich biological media results from the interplay between primary photoionization processes and avalanche amplification of free electrons. Understanding this competition is essential for predicting ablation thresholds under ultrashort-pulse irradiation. In this work, we develop an analytical rate-equation model for the buildup of electron density in water-like biological tissues. It combines photoionization and chromophore ionization into a single seed-generation term, while avalanche ionization is described through a cascade gain factor. This formulation provides a framework for describing cascade electron-impact ionization processes in liquid-like media under strong-field excitation. Our approach gives an analytical expression for the temporal evolution of electron density driven by a Gaussian laser pulse and makes it possible to separate the contributions of direct ionization of water and ionization of chromophore centers. The analytical results are compared with numerical simulations that include carrier diffusion, bimolecular recombination and trapping. The comparison clarifies the roles of seed formation and cascade amplification in the growth of the electron population. The predicted dependence of threshold fluence on pulse duration agrees well with experimental data reported for water-like tissues such as the corneal tissues at a wavelength of 800 nm. The model provides a simple analytical picture of ultrafast plasma formation and electron-driven energy deposition in water-like biological media.
Introduction: Orthopaedic repair outcomes are limited by disrupted cellular mechanotransduction and physiological instability during anaesthesia. Integrating biomechanical signal modulation with stabilising perioperative strategies may enhance tissue healing and reduce postsurgical complications. Methodology: Existing orthopaedic therapies fail to restore native mechanosensory signalling at repair sites, leading to delayed recovery, implant loosening, and reduced function. Additionally, anaesthesia-induced cardiovascular and metabolic changes disrupt regenerative signalling. This paper presents GEM-TRAP, a synergistic cotargeting platform using dual delivery of gene vectors to enhance mechanotransduction and protein regulators to maintain physiological stability during anaesthesia. Smart biomaterial scaffolds enable controlled release at the injury site. Results: In vivo results show improved osseointegration, a 38% increase in load-bearing strength, enhanced neural-mechanical signalling, and a 27% reduction in complications, demonstrating GEM-TRAP's potential for advanced orthopaedic regeneration. The proposed method achieves the osseointegration efficiency of 90%, physiological stability of 92%, mechanical strength recovery of 90%, mitochondrial efficiency of 90%, and postsurgical complications reduced by 40-60%. Conclusion: This study presents GEM-TRAP, a novel cotargeting platform that concurrently enhances cellular mechanotransduction and maintains physiological stability during anaesthesia. By integrating dual therapeutic delivery with smart biomaterial scaffolds, the approach addresses both regenerative and perioperative challenges, offering a new strategy for improving orthopaedic repair and functional recovery.
The ionizations of the 1S state of hydrogenic systems with a nuclear charge of Z = 2 and 3 have been carried out using the hybrid theory. This is a continuation of the work started earlier. The present results are compared with the published cross-sections for Z = 1 [Bhatia, A.K. 2025]. The distortion of the orbit is considered irrespective of the position of the incident particle, whether it is outside or inside the orbit. Only the distortion of the target orbit in the initial state is considered, but the distortion in the final state is not considered. Cross-sections decrease as the nuclear charge increases.
Differential ionization in C6++He collisions is investigated using the single- and two-center wave-packet convergent close-coupling (WP-CCC) method for projectile energies of 1-6 MeV/u. We present three types of singly differential cross-sections (SDCSs) as functions of the ejection angle, ejection energy, and projectile scattering angle. The two-center framework incorporates couplings across all channels as well as electron correlations. Overall, both the single- and two-center WP-CCC results agree well with existing experimental and theoretical data (apart from the first Born ones) for the SDCS as a function of electron energy and the SDCS as a function of ejection angle, laying a foundation for investigation of doubly and fully differential ionization cross-sections. The cross-sections differential in the projectile scattering angle are presented for the first time.
The energy-dependent population of fine quantum states in single electron capture (SEC) reflects the intrinsic collision dynamics. Here we report experimental studies of Ar7+ ions colliding with He in the energy range of 1.05-17.5 keV/u. Owing to the high resolution of a recoil-ion momentum spectrometer, the n-, l-, and spin-state electron capture populations are well resolved, and a strong energy dependence of the SEC cross sections is observed. Most importantly, a clear inversion of the cross-section ratio between the spin-resolved triplet and singlet 3s3d configurations is found, demonstrating a breakdown of spin statistics. Together with recent spin-resolved studies of C3+-He collisions (PRL 133, 173002 (2024)), these results suggest that the breakdown of spin statistics is likely a general feature of charge exchange in open-shell highly charged ion systems.
In Na- through Ca-like ions of Fe, rather low-lying 3d levels feature level lifetimes in the range from picoseconds to many seconds. This lifetime range is somewhat wider than that of the 3p resonance levels of the same ions. When trying to measure such level lifetimes, the width of the range exceeds the capabilities of a single measurement scheme. However, there also is the fundamental problem of multi-exponential decay curves and the reliability of their analysis. This problem has arisen afresh for the analysis of long-lived 3p levels in the ground configurations of many isoelectronic sequences that are replenished by cascades from long-lived 3d levels that have no E1 decay channels, but consequently feature lifetimes of the same order of magnitude as those in the ground configuration. This tutorial addresses the measurement situation for lifetimes of 3d levels in a number of ions of Fe and nearby elements.
