Search Results (23,566)

Colonoscopy is the gold standard for diagnosing and monitoring gastrointestinal diseases. However, bowel preparation, rather than the procedure itself, appears to be the main driver of transient gut microbiota disruption. Available evidence suggests that microbiota alterations after bowel preparation and colonoscopy may persist for days to weeks and may be associated with changes in barrier function, microbial metabolism, and symptom burden in susceptible individuals. This review summarizes current knowledge on the mechanisms underlying microbial disruption induced by bowel preparation, including loss of diversity, shifts in key taxa, impairment of metabolic pathways, and alterations in immunomodulatory metabolites. It also discusses potential clinical consequences and highlights nutritional strategies that may support microbiota recovery, including dietary fiber, polyphenols, and microbiota-targeted approaches. This review also highlights current research gaps and the need for well-designed clinical studies in this field. Full article

Background: Graft-versus-host disease is the most common complication after allogeneic hematopoietic stem cell transplantation. While ocular graft-versus-host disease typically manifests as dry eye syndrome and anterior segment involvement, posterior segment complications are rare. Previously reported posterior segment complications in graft-versus-host disease have been limited to acute presentations with significant functional visual impairment. Methods: A 41-year-old man developed progressive retinal nerve fiber layer and ganglion cell layer loss four years after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. The patient had established chronic graft-versus-host disease with cutaneous involvement and ocular surface disease. Results: Despite preserved visual acuity and visual fields, and only subtle functional involvement on visual evoked potentials, optical coherence tomography revealed significant reduction in retinal nerve fiber layer thickness and ganglion cell layer. Magnetic resonance imaging showed no optic nerve or brain abnormalities. Conclusions: This case describes an uncommon presentation of chronic, subclinical posterior segment involvement in chronic GVHD and suggests that optical coherence tomography may detect progressive structural retinal changes in the absence of clinically evident visual impairment, supporting its potential role in longitudinal monitoring. Full article

This study addresses energy-response prediction in sheet metal forming under small-data conditions, where conventional simulation-based approaches are computationally expensive and data acquisition is limited. We propose an Energy-Informed Neural Network (EINN) framework that integrates energy consistency constraints and a Fenchel–Young duality-based loss to enforce physically consistent learning without relying on explicit governing equations. Using a dataset generated from 54 finite element simulations across 18 materials and three friction conditions, the proposed model demonstrates significant performance improvements. Specifically, EINN achieves an RMSE of 0.0096, MAE of 0.0065, and R² of 0.9778, corresponding to approximately a 48% reduction in RMSE compared to the best baseline model. Compared to an energy-constrained neural network without the Fenchel–Young term, prediction error is reduced by approximately 50% with substantially improved stability. These results indicate that embedding energy-consistent dual structures enhances both prediction accuracy and robustness, providing a practical surrogate modeling approach for process optimization in sheet metal forming under limited data availability. Full article

The cyclic AMP receptor protein (CRP) is a highly conserved global transcriptional regulator that integrates carbon metabolism and environmental adaptation in bacteria. However, its systematic role in the regulation of virulence in K. pneumoniae remains poorly understood; In this study, we constructed a crp deletion mutant (Δcrp) and a complemented strain (c-Δcrp) and employed a combination of in vitro virulence assays, in vivo infection models, transcriptomic profiling, and functional metabolic analyses to dissect the CRP-mediated metabolism–virulence regulatory axis; We show that crp deficiency does not significantly alter susceptibility to clinically relevant antibiotics but markedly impairs biofilm formation, motility, and host cell adhesion and invasion. In murine infection models, the Δcrp strain exhibits significantly reduced pulmonary colonization and lethality. Transcriptomic analysis reveals broad downregulation of phosphotransferase system (PTS)-associated genes, including srlA/srlB/srlE, mtlA and malX. Functional assays further demonstrate that crp loss severely compromises growth on multiple host-relevant carbon sources and is accompanied by aberrant accumulation of intracellular ATP and NADH, indicative of disrupted metabolic homeostasis; Collectively, these findings identify crp as an important regulator associated with PTS-mediated carbon metabolic balance, and virulence-related phenotypes in K. pneumoniae. Accordingly, targeting the CRP–PTS axis may offer a theoretical basis for metabolism-oriented anti-virulence interventions against K. pneumoniae by attenuating pathogenicity. Full article

Theaflavin-3,3′-digallate (TF3), a flavan-3-ol derivative found in black tea, exhibits anti-tumor activity, but its mechanism of action in hepatocellular carcinoma (HCC) remains to be elucidated. Here we systematically delineate how TF3 targets Pin1 to suppress HCC through an integrated approach combining computational simulations, enzyme assay and cell-based assays. TF3 spontaneously occupies the active site of Pin1 with a docking score of −8.9 kcal/mol, inhibiting its PPIase activity (IC₅₀ = 60.33 μmol/L) and yielding a binding constant (K_a) of 3.1 × 10⁵ mol/L. Drug affinity responsive target stability (DARTS) assays further corroborated that TF3 directly engages Pin1 within HCC cells. Functionally, TF3 potently suppressed the viability of HepG2, SK-Hep-1 and Huh-7 cells in both dose- and time-dependent manners (IC₅₀ = 61.22, 14.09 and 69.85 μmol/L at 24 h, respectively), and exhibited a modest selectivity window against the viability of L02 and THLE-2 cells (IC₅₀ = 133.43 and 90.29 μmol/L at 24 h, respectively). In addition, TF3 triggers mitochondrial-mediated apoptosis, evidenced by ROS accumulation, loss of mitochondrial membrane potential, an elevated Bax/Bcl-2 ratio, cytochrome c release and enhanced PARP cleavage, and induces G₂/M phase arrest. It also robustly inhibits HCC cell proliferation, invasion and migration, coinciding with downregulation of proteins governing cell cycle progression and invasive behavior. Transcriptome profiling coupled with enrichment analysis discovered that TF3 treatment differentially regulated 5009 genes, which were prominently enriched in pathways linked to apoptosis, cell cycle control, MAPK and PI3K/AKT signaling pathways. Western blotting analysis revealed that TF3 selectively suppresses phosphorylation of p38 and the PI3K/AKT cascade, activating JNK phosphorylation. In summary, our findings indicate that TF3 suppresses HCC proliferation by targeting Pin1, with attendant modulation of the MAPK and PI3K/AKT pathways, thereby presenting a potential candidate for targeted HCC therapy. Full article

Clear-cell renal cell carcinoma (ccRCC) is characterised by constitutive activation of hypoxia-inducible factors (HIFs) following VHL loss, which contributes to tumour progression and therapeutic resistance. Given the limitations of VEGFR-targeted therapies, we investigated the biological and potential therapeutic relevance of the HIF axis in ccRCC. Nuclear and cytoplasmic HIF1A and EPAS1/HIF2A expression were assessed by immunohistochemistry in tumours from 40 patients and correlated with clinicopathological parameters and cancer-specific survival. The functional effects of HIF pathway inhibitors (GN44028, KC7F2, and FM19G11) and sunitinib were analysed in VHL-mutant 786-O and VHL-wild-type Caki-1 cell lines using SRB viability assay, cell cycle analysis, wound closure assay, and RT-qPCR of HIF-related genes, with comparison to non-malignant HK-2 cells. TCGA-ccRCC data from advanced-stage patients (III–IV, n = 185) were analysed as a complementary transcriptomic context. Nuclear, but not cytoplasmic, HIF1A and EPAS1/HIF2A expression was associated with advanced stage and shorter survival in univariable analyses. GN44028 showed the most pronounced antiproliferative effect under tested conditions and was associated with broad suppression of HIF-related transcription, whereas sunitinib was associated with increased expression of selected HIF-related genes. GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established. Full article

Urban shrinkage, driven by demographic and socioeconomic changes, has become a pressing issue across Europe, particularly in small peripheral towns and semi-urban settlements that have historically relied on a single industry or company. This study investigates the demographic and socioeconomic factors contributing to the multi-dimensional decline, encompassing population loss, economic contraction, and deteriorating socioeconomic conditions in Latvian mono-towns, thereby filling a void in empirical research on urban development in post-socialist contexts. Principal component analysis (PCA) was applied to a set of key demographic and socioeconomic indicators derived from census and administrative data to identify the principal dimensions that drive urban shrinkage. The analysis reveals three principal components explaining 87% of the variance: socioeconomic vitality (57.1%), population change and peripherality (17.2%), and aging society dynamics (12.6%). The results contribute to a nuanced understanding of how mono-functional urban contexts shape the intensity and character of shrinkage. These results establish a basis for specific policy measures designed to promote resilience in small-settlement settings and contribute to the understanding of spatial planning and regional development approaches in the post-socialist urban transition context. This research underscores the need for context-specific approaches to address the multifaceted challenges of urban shrinkage. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder marked by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies, intracellular inclusions enriched in α-synuclein. Synphilin-1 interacts with α-synuclein, localizes to Lewy bodies, and has been implicated in inclusion formation and neuroprotection in cellular and animal models; however, its physiological function in vivo remains poorly defined. Here, we generated and characterized a synphilin-1 knockout (Sph-1 KO) mouse by targeted genetic deletion of the Sph-1 locus and performed a comprehensive phenotyping battery including behavioral testing as well as biochemical, histological, structural, and ultrastructural analyses. Sph-1 KO mice survived to nearly two years of age and showed normal body weight, lifespan, motor performance, learning and memory, anxiety-like behavior, attention, and gross brain morphology. Western blot analyses indicated that levels of α-synuclein and synaptic proteins were largely unchanged. While outer mitochondrial membrane proteins were unaffected, the mitochondrial matrix protein HSP60 was reduced, consistent with altered mitochondrial proteostasis in the absence of synphilin-1. Strikingly, histochemical analyses, magnetic resonance imaging, and electron microscopy revealed early-onset hydrocephalus in Sph-1 KO mice associated with severe loss and disorganization of motile ependymal cilia in the ventricular lining, a cell type that normally expresses high levels of synphilin-1. Ultrastructural and immunohistochemical analyses revealed disrupted ependymal architecture, mislocalization of acetylated α-tubulin to the cytoplasm, cellular swelling, and enlarged, aberrant mitochondria, whereas cortical neurons appeared largely structurally unaffected. Together, these findings identify synphilin-1 as a key regulator of microtubule organization and cytoskeletal/organelle homeostasis in ependymal cells, required to maintain motile ciliogenesis, cerebrospinal fluid flow, and ventricular integrity. This unexpected role for synphilin-1 in ciliated brain epithelia, along with a reduction in the critical mitochondrial chaperone HSP60, broadens our understanding of synphilin-1 biology and provides a new framework for its potential relevance to PD-associated pathology. Full article

In this work, we demonstrate that both carbon nanotubes (CNT) and graphene nanosheets (G) were successfully modified by π-stacking interactions with a pyrene derivative (PY), yielding the functionalized nanofillers CNT-PY and G-PY, which were subsequently dispersed within an aeronautical epoxy matrix. This functionalization is highly effective in preserving the remarkable electronic properties of carbon nanotubes and graphene nanosheets. At the same time, the non-covalent functionalization reduces the resin viscosity, enabling a more effective dispersion of the nanofillers. This results in improved rheological behavior and an overall enhancement of the structural performance of the nanocomposites compared to the resin containing unfunctionalized carbon nanofillers (CNT and G). Additional improvements are also observed in electrical properties, self-healing efficiency, and thermal stability. In particular, the samples containing functionalized carbon nanotubes (TBD + 1%CNT-PY) and functionalized graphene nanosheets (TBD + 1%G-PY) exhibit higher conductivities—0.391 S/m and 0.1 S/m, respectively—than the samples loaded with unfunctionalized carbon nanotubes (TBD + 1%CNT) and unfunctionalized graphene nanosheets (TBD + 1%G), which show conductivity values of 0.292 S/m and 4.82 × 10⁻³ S/m, respectively. The functionalized graphene nanosheets (G-PY) display significantly greater thermal stability, with degradation temperatures reaching 670 °C, compared to 310 °C for unfunctionalized ones (G). The functionalized carbon nanotubes (CNT-PY) show a 10% weight loss at 520 °C due to the degradation of the pyrene groups. Significant improvements in the final properties can be achieved when carbon-based nanofillers are homogeneously dispersed in the matrix and the external load is efficiently transferred through strong filler–polymer interfacial interactions, leading to composites with superior characteristics suitable for advanced applications. Tunneling Atomic Force Microscopy (TUNA) highlights the morphological features of the two types of carbon nanofillers, their dispersion within the polymer matrix and the effect of the functionalization on the electrical pathways and conductivity of the samples at both the micro- and nanometer-scale. The measured electrical conductivities are consistent with the electric currents detected at the micro/nanoscale. Full article

Introduction: Early warning systems reduce losses when risk knowledge, forecasting, communication, and response planning operate as an end-to-end chain, yet Gulf Coast warning practice often treats hazard dynamics, ecosystem change, and social vulnerability as separate domains. This study mapped operational early warning systems for climate-relevant hazards across Louisiana, Texas, Mississippi, Alabama, and Florida and examined whether ecosystem protective functions and social vulnerability were integrated into warning thresholds, dissemination design, and preparedness planning. Methods: I conducted a scoping review using the Web of Science Core Collection and Scopus for publications from 2020 through 18 January 2026 and targeted searches of NOAA/NWS/NHC, FEMA IPAWS, CDC/ATSDR SVI, IOOS/GCOOS, USGS, and state coastal agency portals between 15 September 2025 and 18 January 2026. Of 861 identified records, 440 duplicates were removed, 421 titles and abstracts were screened, 121 full texts were assessed, and 25 sources were included in the final charting and synthesis. Results: The review identified 11 operational systems and related platforms spanning the four early warning pillars, but routine socio-ecological integration remained limited. Louisiana showed the strongest documentation of ecosystem monitoring through CPRA and CRMS, while Florida and Texas showed more developed evacuation and dissemination interfaces. Mississippi and Alabama were represented by thinner monitoring and implementation records in the included sample. Across states, ecosystem loss and social vulnerability were used more often as planning context than as repeatable inputs to thresholds, message tailoring, or assistance triggers. Discussion: Gulf Coast practices can be strengthened through formal protocols that connect ecosystem condition and vulnerability indicators to impact-based briefings, multilingual and accessible alert workflows, and tract-sensitive preparedness actions. The findings indicate that implementation can advance by linking existing datasets to defined operational decisions and by evaluating warning performance through reach, accessibility, comprehension, and action feasibility, as well as technical accuracy. Full article

Strontium (Sr) is an essential trace element that plays a critical role in bone health, calcium absorption, cardiovascular function, and nerve function. In this experiment, fresh-cut peaches were treated with different concentrations of strontium chloride (SrCl₂) to study the effects of SrCl₂ on the antioxidant system, endogenous nitric oxide (NO) metabolism, and endogenous hydrogen sulfide (H₂S) metabolism, aiming to investigate the regulatory mechanism of Sr on postharvest quality of horticultural products. The results showed that, compared with the control, 320 μM SrCl₂ significantly suppressed the respiration rate by 15.10% and delayed the respiratory peak by 2 days. Meanwhile, SrCl₂ treatment effectively inhibited the rise in electrolyte leakage (EL), color difference, and weight loss, and delayed the decline in fruit firmness. In addition, SrCl₂ treatment significantly up-regulated the gene expression levels and enzyme activities of the antioxidant system, the AsA-GSH cycle, NO, and H₂S metabolism, which reduced the loss of antioxidants, enhanced the ability of fruits to scavenge hydrogen peroxide (H₂O₂), hydroxyl radical (˙OH), and superoxide anion (O₂⁻˙), and lowered the malondialdehyde (MDA) content. It suggests that SrCl₂ treatment has a positive effect on maintaining the postharvest quality of fresh-cut peaches, which appears to be associated with increased endogenous production of NO and H₂S, thereby enhancing antioxidant system activity. Full article

Lubricants are essential for water-based drilling fluids. Catechol-based lubricants provide improved lubrication performance owing to their strong adhesion ability through the formation of coordination bonds inspired by mussel adhesion. However, the conventional synthetic ester and amide lubricants suffer from loss of adhesive capability due to hydrolysis and autoxidation. Inspired by mussels and melanin biosynthesis, a biomimetic strategy was developed to synthesize a high-adhesion lubricant with good stability via thiol-quinone Michael addition to restore and stabilize the catechol moiety. Bisphenol A was oxidized to the corresponding quinone using 2-iodoxybenzoic acid. Subsequent Michael addition reaction with 1-octadecanethiol produced a thiol-functionalized lubricant containing catechol moieties and long alkyl chains through an S-catecholyl linkage. Biomimetic principles were incorporated into both the molecular structure and the synthetic route, emulating the structural and functional features of mussel adhesion and melanin biosynthesis. Octadecanethiol provided sulfur-containing extreme-pressure functionality and contributed to strong adsorption on metal surfaces. The molecular structure was confirmed by FTIR, ¹H NMR, and ¹³C NMR. The thiol-functionalized lubricant formed strong coordination with Fe³⁺ and Fe²⁺ ions across a wide pH range, with an apparent complexation stoichiometry of 1:1 and conditional stability constants of 4.09 and 5.02, respectively. Bis-coordination formed a cross-linking network. It exhibited good resistance toward autoxidation and thermal stability up to 350 °C. In bentonite-based drilling fluids, the extreme pressure lubrication coefficient and adhesion coefficient at a 1% addition were 0.06 and 0.07, respectively. The coefficient of friction and wear scar diameter were 0.09 and 0.63 mm, respectively. The increased contact angle confirmed strong adsorption of the lubricant on metal surfaces. The lubricant combined strong adhesion, high stability, and excellent compatibility with drilling fluids, highlighting its potential as an advanced biomimetic lubricant. This biomimetic thiol-quinone addition strategy provides an effective approach to overcome the instability of conventional catechol-based lubricants. Full article

Accurate State of Charge (SOC) estimation is critical for the safety and efficiency of Battery Management Systems (BMS). While data-driven methods have shown promise, they often exhibit limited generalization capability due to the lack of physical constraints. Incorporating symmetry in the battery, such as through the use of Physics-Informed Neural Networks (PINNs), can mitigate this issue. However, PINNs typically rely on integer-order equivalent circuit model differential equations, which fail to accurately describe the complex electrochemical relaxation processes. To bridge this gap, we propose a novel Fractional Differential Physics-Informed Neural Network (FDE-PINN) framework. Unlike traditional approaches, this method embeds a Fractional-Order Equivalent Circuit Model (FO-ECM) into the Gated Recurrent Unit (GRU) architecture to explicitly capture the anomalous diffusion and long-memory effects inherent in battery polarization. Specifically, the network is trained by minimizing a composite loss function that integrates the data fitting error with residuals from fractional-order governing equations, including Coulomb counting and fractional voltage dynamics. Extensive experiments on the Panasonic 18650PF dataset and CALCE A123 dataset verify the method’s superiority. Results demonstrate that the proposed FDE-GRU model achieves an average MSE of $14.29\times {10}^{-4}$ (with an MAE of 2.43% and RMSE of 3.23%) on the NCA chemistry and $26.24\times {10}^{-4}$ (with an MAE of 3.75% and RMSE of 5.09%) on the LiFePO₄ chemistry, significantly outperforming traditional methods by reducing the estimation error by 35.6% and 26.2% compared to the standard GRU, respectively. Full article

Background/Objectives: Impairment in pulsatile insulin release contributes to insulin resistance and is one of the earliest markers of developing type 2 diabetes. Insulin delivered to the liver in pulses has a stronger glucose-lowering effect than continuous insulin delivery. Whether pulsatility benefits the islet itself is an open question. We previously showed that reducing glucokinase activity with the glucokinase inhibitor D-mannoheptulose (MH) improves function in islets exposed to prolonged hyperglycemic conditions. In this study, we test whether pulsatile vs. continuous delivery impacts the effectiveness of MH in islets. Methods: Islets were exposed to high-glucose conditions (20 mM glucose) for 24 or 48 h to induce early adaptations to hyperglycemia. We then used a specially designed perifusion system to impose pulsatile activity by exposing mouse islets to 3 min of MH in 20 mM glucose and 3 min of only high levels of glucose. Islets given intermittent MH for 18 h were compared with continuous delivery of MH at a full (2.5 mM) or half (1.25 mM) dose. Results: MH delivered by the forced oscillatory system reversed the effects of hyperglycemia and restored glucose sensing more effectively than continuous delivery. Specifically, fura-2AM imaging of intracellular calcium showed that islets given pulsatile MH had greater reductions in the elevated basal calcium caused by hyperglycemic conditions, improved the glucose stimulation index, and improved phase 0 response (indicating glucose-stimulated calcium uptake by the endoplasmic reticulum). Conclusions: These findings suggest that the loss of oscillatory glucose metabolism in islets contributes directly to beta-cell dysfunction. Full article

The sigma-1 receptor (S1R) is an endoplasmic reticulum (ER)-resident protein enriched at the mitochondria-associated ER membranes (MAMs) that supports ER homeostasis, preserves mitochondrial function, and enhances cell survival under stress. Disruptions of MAM integrity and prolonged ER stress are well-recognized pathological features of amyotrophic lateral sclerosis (ALS), contributing to motor neuron dysfunction and degeneration. In this study, we evaluated the protective effects of pridopidine, a highly selective and potent S1R agonist currently in clinical development for Huntington’s disease (HD) and ALS, using neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs) from a patient with sporadic ALS. Exposure of ALS NPCs to the ER stressor tunicamycin increased the ER stress markers binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), disrupted mitochondrial membrane potential, upregulated expression of the mitochondrial apoptotic marker, BAX, increased caspase-3 activation, and reduced cell viability. Pridopidine significantly attenuated tunicamycin-induced BiP and CHOP expression in a biphasic, dose-dependent manner (with maximal efficacy at 1 µM), consistent with the typical pharmacology of S1R agonists. Pridopidine restored mitochondrial membrane potential, reduced mitochondrial apoptotic signaling, shown by decreased BAX expression and caspase-3 activation, and improved survival of ALS-NPCs under ER stress. Co-treatment with the selective S1R antagonist, NE-100, attenuated these effects, supporting an S1R-mediated mechanism of action for pridopidine. Together, these results demonstrate that S1R activation by pridopidine mitigates ER-stress-induced mitochondrial dysfunction and cell loss in ALS-NPCs, resulting in enhanced survival of NPCs supporting the therapeutic potential of pridopidine in ALS. Full article