Search Results (3,254)

Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal stem cells (MSCs) represents the most promising approach in dentistry. This study assessed the bone-augmenting capacity at bone defect sites in inbred rats by seeding dedifferentiated fat (DFAT) cells onto a cotton-like bone graft scaffold composed of β-TCP and poly(L-lactic-co- glycolide) (PLGA), which was subsequently wrapped around titanium. As a control, cotton-like bone graft material without cells was used and wrapped around and transplanted. Four weeks post-implantation, computed tomography (CT) images of the DFAT group revealed a 1.25-fold enhancement in hard tissue formation compared to the control group. Histological analysis revealed compact structure in a dark red color surrounding the cotton-like bone graft material was observed on the titanium surface of DFAT group. Histomorphometric analysis revealed that the amount of hard tissue generated in the DFAT group was approximately 2.5 times higher than that observed in the control group. Moreover, this mineralized tissue demonstrated properties analogous to those observed in cortical bone. Collectively, these findings indicate that the composite of DFAT cells and cotton-like bone graft material holds potential for bone augmentation applications and represents a promising approach for regenerative therapies within the orofacial region. Full article

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior. These limitations have spurred the development of structurally diverse and safer HDAC inhibitors incorporating alternative ZBGs. This review provides a comprehensive analysis of recently developed HDAC inhibitors reported in the last few years, emphasizing their structure–activity relationships (SARs), chemical scaffolds, and binding features—including cap, linker, and ZBG motifs. Both hydroxamate-based and non-hydroxamate inhibitors, such as benzamides, hydrazides, and thiol-containing analogs, are critically evaluated. Moreover, the potency and selectivity profiles of these inhibitors are summarized across different cancer and normal cell lines, as well as specific HDAC isoforms, providing a clearer understanding of their therapeutic potential. Emerging dual-target HDAC inhibitors, such as HDAC–tubulin, HDAC–PI3K and HDAC–CDK hybrids, are also discussed for their synergistic anticancer effects. Full article

In human medicine, the 2025 International Society for the Study of Vascular Anomalies (ISSVA) classification distinguishes localized lymphatic malformations from systemic disorders referred to as complex lymphatic anomalies (CLAs), including generalized lymphatic anomaly (GLA) and central conducting lymphatic anomaly (CCLA). GLA is characterized by multifocal proliferation of dilated lymphatic channels infiltrating soft tissues and visceral organs, whereas CCLA involves structural or functional abnormalities of the central lymphatic pathways such as the thoracic duct commonly resulting in chylous effusion. Reports of systemic lymphatic disease in veterinary species are exceedingly rare. A five-month-old intact male domestic shorthair cat presented with progressive dyspnea and was diagnosed with chylothorax and chylous ascites. Computed tomography (CT) revealed contrast leakage from both the thoracic duct and aortic hiatus, along with diffuse subcutaneous edema, indicating a systemic lymphatic disorder. Histopathology demonstrated proliferative lymphatic channels within the subcutaneous tissues, consistent with GLA, while imaging findings suggested concurrent CCLA, supporting classification as an overlapping CLA phenotype. Despite medical and surgical interventions, the cat developed progressive edema and recurrent pleural effusion and ultimately died. This case demonstrates that cats can develop systemic lymphatic disorders analogous to human CLAs and highlights the diagnostic value of CT lymphangiography. Furthermore, it underscores the utility of applying the ISSVA classification to enhance comparative understanding of lymphatic diseases in veterinary medicine. Full article

Background: Recent research suggests that damage to right hemisphere regions homotopic to the left hemisphere language network affects language abilities to a greater extent than previously thought. However, few studies have investigated acute disruption of language after lesion to the right hemisphere. Here, we examined lesion correlates of acute speech deficits following left and right hemisphere ischemic stroke to clarify the neural architecture underlying early language dysfunction. Methods: We retrospectively analyzed 410 patients (225 left, 185 right hemisphere lesions) from the Stroke Outcome Optimization Project dataset. Presence and severity of speech deficits was measured using the National Institute of Health Stroke Scale Best Language subscore within 48 h of onset. Manual lesion masks were derived from clinical MRI scans and normalized to MNI space. Lesion-symptom mapping was conducted using voxelwise and region-of-interest analyses with permutation correction (5000 iterations; p < 0.05), controlling for total lesion volume. Results: Speech deficits were observed in 53.7% of the cohort (58.2% left, 48.1% right hemisphere lesions). In the full sample, the presence of speech deficits was associated with bilateral subcortical and perisylvian damage, including the external and internal capsules, insula, putamen, and superior fronto-occipital fasciculus. Severity of speech deficits localized predominantly to left hemisphere structures, with peak associations in the external capsule (Z = 6.39), posterior insula (Z = 5.64), and inferior fronto-occipital fasciculus (Z = 5.43). In the right hemisphere cohort, the presence and severity of speech deficits were linked to homologous regions, including the posterior insula (Z = 3.70) and external capsule (Z = 3.63), although with smaller effect sizes relative to the left hemisphere cohort. Right hemisphere lesions resulted in milder deficits despite larger lesion volumes compared with left hemisphere lesions. Conclusions: Acute speech impairment following right hemisphere stroke is associated with damage to a homotopic network encompassing perisylvian cortical and subcortical regions analogous to the dominant left hemisphere language network. These findings demonstrate that damage to the right hemisphere consistently results in acute speech deficits, challenging the traditional left-centric view of post-stroke speech impairment. These results have important implications for models of bilateral language representation and the neuroplastic mechanisms supporting language recovery. Full article

The Tarim Basin is currently the largest petroliferous basin in China, with hydrocarbons primarily hosted in Ordovician marine carbonate paleokarst fracture–vug reservoirs—a typical example being the Tahe Oilfield located in the northern structural uplift of the basin. The principle of “the present is the key to the past” serves as a core method for studying paleokarst fracture–vug reservoirs in the Tahe Oilfield. The deep and ultra-deep carbonate fracture–vug reservoirs in the Tahe Oilfield formed under humid tropical to subtropical paleoclimates during the Paleozoic Era, belonging to a humid tropical–subtropical paleoepikarst dynamic system. Modern karst types in China are diverse, providing abundant modern karst analogs for paleokarst research in the Tarim Basin. Carbonate regions in Eastern China can be divided into two major zones from north to south: the arid to semiarid north karst and the humid tropical–subtropical south karst. Karst in Northern China is characterized by large karst spring systems, with fissure–conduit networks as the primary aquifers; in contrast, karst in Southern China features underground river networks dominated by conduits and caves. From the perspective of karst hydrodynamic conditions, the paleokarst environment of deep fracture–vug reservoirs in the Tarim Basin exhibits high similarity to the modern karst environment in Southern China. The development patterns of karst underground rivers and caves in Southern China can be applied to comparative studies of carbonate fracture–vug reservoir structures in the Tarim Basin. Research on modern and paleokarst systems complements and advances each other, jointly promoting the development of karstology from different perspectives. Full article

The replacement of ionizable functional groups that are predominantly charged at physiological pH with neutral bioisosteres is a common strategy in medicinal chemistry; however, its impact on binding affinity is often context-dependent. Here, we investigated a series of amide derivatives of a glycomimetic E-selectin ligand, in which the carboxylate group of the lead compound is substituted with a range of amide and isosteric analogs. Despite the expected loss of the salt-bridge interaction with Arg97, several amides retained or even improved the binding affinity. Co-crystal structures revealed conserved binding poses across the series, with consistent interactions involving the carbonyl oxygen of the amide and the key residues Tyr48 and Arg97. High-level quantum chemical calculations ruled out a direct correlation between carbonyl partial charges and affinity. Instead, a moderate correlation was observed between ligand binding and the out-of-plane pyramidality of the amide nitrogen, suggesting a favorable steric adaptation within the binding site. Molecular dynamics (MD) simulations revealed that high-affinity ligands exhibit enhanced solution-phase pre-organization toward the bioactive conformation, likely reducing the entropic penalty upon binding. Further analysis of protein–ligand complexes using Molecular mechanics/Generalized born surface area (MM-GB/SA) decomposition suggested minor lipophilic contributions from amide substituents. Taken together, this work underscores the importance of geometric and conformational descriptors, beyond classical electrostatics, in driving affinity in glycomimetic ligand design and provides new insights into the nuanced role of amides as carboxylate isosteres in protein–ligand recognition. Full article

Plant-based meat analogs, particularly those produced by high-moisture extrusion, are prone to quality deterioration during frozen storage due to poor freeze–thaw stability. This study aimed to develop a synergistic stabilization strategy for soy protein isolate (SPI)-based extrudates using glucose oxidase (GO), phytase (PA), and tamarind gum (TG). The effects of individual additives (GO, PA, TG) and their combination (GO + TG) were systematically evaluated over seven freeze–thaw cycles, with a pure soybean-protein meat analog (PSM) as a control. The results showed that repeated freeze–thaw cycles severely degraded the control groups, leading to reduced water-holding capacity (WHC), increased hardness, and color darkening. While all additives mitigated these changes, the GO + TG combination exhibited the most pronounced protective effect, maintaining the highest WHC (0.993 ± 0.000), optimal texture (hardness 66.0 ± 0.0 N, elasticity 3.7 ± 0.0 mm), and minimal color variation. Structural analyses revealed that GO + TG effectively suppressed protein oxidation, minimized sulfhydryl loss, preserved protein secondary and tertiary structures, and inhibited the conversion of immobilized water to free water. The synergistic mechanism is attributed to the formation of a dual-network structure, wherein GO enhances covalent cross-linking and TG provides steric stabilization. This study offers a practical and effective approach for enhancing the freeze–thaw stability of extruded plant-based meat products, with potential industrial applications. Full article

Background: Eczematous dermatitis refers to a group of inflammatory skin disorders—including seborrheic, atopic, and contact dermatitis—characterized by epidermal barrier dysfunction and chronic inflammation. Disrupting the itch–scratch cycle and reversing microscopic skin changes are key to improving patient outcomes and quality of life. Aims: This study aimed to assess the clinical and microscopic effects of a topical medical device containing N-butanoyl glutathione (GSH-C4) and hyaluronic acid in patients with inflammatory eczematous dermatitis, combining clinical scores with in vivo confocal and OCT imaging. Methods: A prospective clinical trial enrolled 30 patients with active eczematous lesions. Participants applied a GSH-C4/hyaluronic acid-based product (GSEBA^®) for 28 days. Clinical improvement was evaluated at baseline, day 14, and day 28 using the Investigator’s Global Assessment (IGA), a Visual Analog Scale (VAS) for itching, and a self-reported index of disease impact on quality of life (IDL). Microscopic changes were assessed using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Results: After 28 days, the mean IGA score improved from 2.48 to 0.18 (p < 0.001), VAS itching score decreased from 4.52 to 0.32 (p < 0.001), and IDL dropped from 4.86 to 0.79 (p < 0.001). RCM analysis showed significant reductions in key inflammatory features such as spongiosis, vesiculation, and inflammatory infiltrate. OCT revealed a significant decrease in vascularization at 150 μm depth, with no change in collagen density. Conclusions: The GSH-C4/hyaluronic acid-based mousse (GSEBA^®) demonstrated strong clinical efficacy and excellent tolerability in managing eczematous dermatitis. It effectively reduced both symptoms and microscopic markers of inflammation without compromising dermal structure. Full article

Background/Objectives: Spinal cord stimulation (SCS) is an established therapy for chronic pain, but uncertainties remain regarding long-term real-world outcomes and the role of standardized selection pathways. This study aimed to evaluate real-world, longitudinal outcomes of SCS over 24 months within a structured clinical pathway, focusing on pain intensity, neuropathic symptoms, and health-related quality of life. Methods: A single-center, retrospective observational cohort study was conducted at the Fondazione Istituto G. Giglio (Cefalù, Italy). Data were drawn from the continuing, prospective institutional “SCS Pathway” and included consecutive patients implanted between May 2021 and September 2024. Eligible patients were ≥18 years of age with chronic pain refractory to conventional medical management. Outcomes included pain intensity (VAS, visual analog scale), neuropathic features (DN4, douleur neuropathique 4), and health-related quality of life (EQ-5D, EuroQol 5 Dimensions), assessed at baseline and 3, 6, 12, 18, and 24 months post-implantation. Multilevel models with full information maximum likelihood (FIML) were applied to repeated measures. Results: Seventy-six patients were included (mean age 67.3 ± 10.3 years; 39.5% female). The most frequent diagnoses were post-surgical pain syndrome (42.1%, 32/76) and chronic back and leg pain (40.8%, 31/76). 42.1% (32/76) had previous spine surgery, and 78.9% (60/76) reported neuropathic pain. Across 452 observations, mean VAS scores decreased from 7.9 ± 0.7 at baseline to 3.1 ± 1.1 at 3 months (61% reduction, p < 0.001), with sustained benefit at 24 months (4.5 ± 1.5; 43% reduction, p < 0.001). DN4 scores improved from 7.4 ± 0.8 to 3.2 ± 1.0 at 3 months (56% reduction, p < 0.001), with persistent decreases at 24 months (4.2 ± 1.2; 43% reduction, p < 0.001). EQ-5D improved from 22.8 ± 6.6 at baseline to 70.2 ± 10.6 at 3 months (increase of 208%, p < 0.001), with clinically meaningful gains sustained at 24 months (55.4 ± 13.7, increase of 143%, p < 0.001). Conclusions: In this real-world cohort, SCS therapy results in sustained, clinically significant improvements in pain, neuropathic symptoms, and quality of life. Findings highlight the value of structured selection and follow-up pathways. These data provide a benchmark for multicenter studies linking standardized referral frameworks to long-term, patient-centered outcomes. Full article

Prussian blue (PB) and its analogs (PBAs) are interesting materials for electrochemical applications due to their tunable redox chemistry and open framework structure. In this study, hexacyanoferrates (HCF) containing iron (FeHCF), cobalt (CoHCF), and nickel (NiHCF) were synthesized via potentiostatic electrodeposition. Cyclic voltammetry revealed distinct redox behaviors. Morphological characterization (SEM, EDX) demonstrated uniform, pyramidal film growth for FeHCF and CoHCF. Otherwise, NiHCF presented a cracked film with cubic clusters on top due to residual stress. Despite this, homogeneous element distribution was found for all samples. Structural characterization (TEM and XRD) confirmed a cubic lattice crystal structure for all films, with systematic lattice contraction from Fe to Co to Ni due to decreasing atomic radius. Raman and XPS data revealed a shift toward Fe²⁺ dominant oxidation states and modifications in C≡N bonding, with the influence of K⁺ and water occupancy in the PBAs framework. These findings illustrate how metal substitution and deposition parameters can tune the structural and electrochemical properties of PBA films, presenting a strategic route to design tailored electrodes. Full article

This research conducts a comparative analysis of the Environmental Impact Assessment’s (EIA’s) legal frameworks in Laos and China, utilising a qualitative methodological approach rooted in comparative law. This research systematically examines primary legal documents, case studies from the hydropower and mining sectors, and recent government data to evaluate the two systems based on three core criteria: the robustness of the legal structure, the effectiveness of enforcement mechanisms, and the depth of public participation. The analysis indicates that although both countries require Environmental Impact Assessments (EIAs), China’s framework is more structured and efficient, as demonstrated by its clearer legal hierarchy, strict penalties for non-compliance, and established public disclosure procedures. In contrast, Laos’s framework, although established, is marked by its early stage of development, evident in fragmented legislation, limited enforcement due to capacity constraints, and reduced public engagement. The study contributes by providing a direct bilateral comparison and empirically demonstrating how institutional divergences account for disparities in environmental outcomes and foreign investment. Recommendations are provided to improve transparency, enforcement capabilities, and substantive public engagement in both nations. This research is based on comparative legal theory and institutional analysis to transcend a mere descriptive narrative. It utilises a qualitative comparative methodology that combines doctrinal research of legal texts with practical case studies from the hydropower and mining industries. This method enables us to systematically investigate how differing institutional capacity, enforcement mechanisms, and governance models between an emerging and a developed system account for variations in EIA outcomes. The study questions are formulated to evaluate theoretical claims regarding the influence of legal frameworks and administrative authority on the attainment of good environmental governance, providing a transferable analytical model for analogous developing environments. Full article

The assessment of Chinese text readability plays a significant role in Chinese language education. Due to the intrinsic differences between alphabetic languages and Chinese character representations, the readability assessment becomes more challenging in terms of the language’s inherent complexity in vocabulary, syntax, and semantics. The article proposed the conceptual analogy between Chinese readability assessment and music’s rhythm and tempo patterns, in which the syntactic structures of the Chinese sentences could be transformed into an image. The Chinese Knowledge and Information Processing Tagger (CkipTagger) tool developed by Sinica-Taiwan is utilized to decompose the Chinese text into a set of tokens. These tokens are then refined through a user-defined token pool to retain meaningful units. An image with part-of-speech (POS) information will be generated by using the token versus syntax alignment. A discrete cosine transform (DCT) is then applied to extract the temporal characteristics of the text. Moreover, the study integrated four categories: linguistic features–type–token ratio, average sentence length, total word, and difficulty level of vocabulary for the readability assessment. Finally, these features were fed into the Support Vector Machine (SVM) network for the classifications. Furthermore, a bidirectional long short-term memory (Bi-LSTM) network is adopted for quantitative comparisons. In simulation, a total of 774 Chinese texts fitted with Taiwan Benchmarks for the Chinese Language were selected and graded by Chinese language experts, consisting of equal amounts of basic, intermediate, and advanced levels. The finding indicated the proposed POS with the linguistic features work well in the SVM network, and the performance matches with the more complex architectures like the Bi-LSTM network in Chinese readability assessments. Full article

Antibodies against low-molecular-weight compounds exhibit cross-reactivities (CRs) with their structural analogs, varying by orders of magnitude for different substances. This variability limits the informativeness of antibody applications as analytical reagents and for other aims when samples contain several members of the same family, their derivatives, or partial degradation products. Therefore, there is a demand to find some criteria for understanding the relationships between the structural characteristics of antigens of a given chemical class and their immunochemical activity. This study presents an experimental and theoretical investigation of the properties of a monoclonal antibody (MAb) against the S-stereoisomer of gatifloxacin, a member of the widely used (fluoro)quinolone (FQ) family of antibiotics, characterized by high structural diversity. The aim was to determine FQs that form complexes with MAb and suggest a methodology to predict their CRs in silico. For this, the interaction of MAb with 26 FQs was studied using the enzyme-linked immunosorbent assay and presented as CR values to the target antigen. The most pronounced CRs were observed for lomefloxacin, sarafloxacin, and ciprofloxacin. Molecular dynamics (MD) simulations were performed to identify differences in analyte interactions at the MAb antigen-binding site, which determines binding affinity. It has been shown that molecular docking fails to discriminate cross-reactive from non-cross-reactive compounds because FQs have similar cores. Therefore, advanced analysis of MD trajectories was carried out. It allowed for clarification of the dynamic features of analyte–antibody interactions responsible for binding. It was shown by the dynamical network analysis that the sum of betweenness centrality between a node corresponding to the quinolone ring and nodes representing MAb amino acids is higher for cross-reactive haptens. The found regularities can be transferred to other analyte–antibody systems as a binary classifier that discriminates cross-reactive and non-cross-reactive compounds. Full article

No pharmacological interventions exist that can restore or preserve auditory function in the mammalian cochlea. Auditory hair cells (HCs) do not spontaneously regenerate, leading to permanent hearing loss. In non-mammalian vertebrates, HC regeneration happens through proliferation and differentiation of their clonally related supporting cells (SCs). The present study supports the potential of quinoxaline (Qx), a nonsteroidal anti-inflammatory compound, to stimulate SC proliferation in the auditory sensory epithelium, a process that may prime the tissue for future HC regeneration. We synthesized a series of Qx derivatives by introducing various substitutions, ranging from hydrophilic to lipophilic. Seventy analogs were generated and tested in vitro and in vivo. Among those, only one (Qx-100) exhibited the best medicinal chemistry profile and was further modified to expand the structure–activity relationship of the chemotype, develop additional analogs, and optimize potency, bioavailability, and in vivo efficacy. Ten new lead variants were generated. Of those, Qx-294 and Qx-301 demonstrated promising in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) profiles and were selected for further testing. Overall, both compounds were rapidly absorbed in zebrafish and mice and promoted cell proliferation in vitro and in vivo without signs of apoptosis, supporting their potential for sensory HC regeneration. Full article

In the face of the urgent need for sustainable practices in the coal industry, we propose a novel green cut-and-fill mining method aimed at achieving material self-sufficiency and mitigating overburden subsidence. This method leverages the goaf roof as an in situ filling material, integrating long-wall caving mining efficiency with partial filling techniques. Through laboratory analog material modeling, numerical simulations, and structural mechanics modeling, we compare the performance of cut-and-fill mining and traditional caving mining methods. The results show that the cut-and-fill method offers more uniform and controlled deformation behavior. Specifically, vertical and horizontal displacements along 40 m survey lines are significantly reduced, with a maximum reduction on the order of millimeters, compared to caving mining. Furthermore, the floor stress concentration coefficient is lower, and the total number of fractures decreases, with shear fractures reduced by 8.8% and tensile fractures reduced by 66.9%. The gangue column in the cut-and-fill method effectively supports the goaf roof, preventing fracture formation and extending the deformation time. The results demonstrate the effectiveness of the cut-and-fill method for subsidence control, suggesting its potential for achieving green and sustainable coal mining practices. Full article