Search Results (48)

Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer’s disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25–35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer’s pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer’s disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders. Full article

Background and Objectives: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed metabolic bariatric surgery procedures worldwide. However, conventional LSG generally requires liver retraction for adequate visualization of the operative field. This study aimed to evaluate the feasibility, perioperative safety, and metabolic outcomes of a modified three-port LSG technique performed without the use of a liver retractor. Materials and Methods: This retrospective single-center cohort study included 2000 consecutive individuals with obesity who underwent three-port laparoscopic sleeve gastrectomy between January 2020 and December 2023. All procedures were performed without mechanical liver retraction by two experienced bariatric surgeons. Operative outcomes, postoperative complications, weight loss parameters, metabolic variables, and histopathological findings were evaluated during a 12-month follow-up period. All included patients completed the predefined follow-up schedule. Postoperative complications were classified according to the Clavien–Dindo classification system. Results: The mean operative time, defined as skin-to-skin duration, was 30 ± 15 min, and the median hospital stay was 2.3 days. No conversion to open surgery, additional trocar placement, or rescue liver retractor use was required. The overall complication rate was 9.4%, with most complications classified as Clavien–Dindo grade I–II. Reoperation was required in three patients (0.15%), and no mortality was observed. Significant metabolic improvements were detected following surgery. Mean HbA1c levels decreased from 7.23% preoperatively to 5.67% at 12 months (p < 0.001), while BMI decreased from 42.6 kg/m² to 28.7 kg/m² (p < 0.001). Excess weight loss and total weight loss at 12 months reached 82.4% and 34.2%, respectively. Diabetes remission was achieved in 65.4% of patients with baseline type 2 diabetes mellitus. Continuous glucose monitoring findings demonstrated reduced postoperative glycemic variability. Conclusions: Three-port laparoscopic sleeve gastrectomy performed without a liver retractor appears to be a feasible and effective surgical approach when performed by experienced bariatric surgeons. The technique was associated with acceptable perioperative safety and favorable metabolic outcomes. However, because of the retrospective single-center design and absence of a conventional comparison group, definitive conclusions regarding superiority or equivalence to standard techniques cannot be established. Prospective multicenter comparative studies are required to validate these findings. Full article

Background: Contextual interference (CI), defined as interleaved practice, improves motor skill learning in powerlifters. However, previous protocols lacked ecological validity. This study evaluated an alternative, highly specific CI exercise (the seal row) to provide a more practical approach for powerlifting routines. Methods: Fifteen powerlifters (10 males and 5 females, age: 23 ± 2 years, 1RM: 78 ± 32 kg) were randomized in a high CI group (HCI) and low CI group (LCI) undergoing a 6-week training intervention. Powerlifters were tested on their bench press exercise strength and technical execution. Technical execution was assessed using a 13-item Likert scale. Results: Strength significantly increased in both groups (F (3.32, 46.5) = 9.553, p < 0.05, pes = 0.42). Global technique analysis showed a group × time interaction (F (4, 952) = 2.547, p = 0.038). A significant group × time interaction occurred for scapular adduction/retraction (F (4, 52) = 3.753, p = 0.009), with the HCI group showing greater improvement. Conclusions: Alternating a primary task (bench press) with antagonist overloads (seal row) improves technical execution over six weeks without hindering strength gains. These findings support practical CI strategies in resistance training to optimize skill acquisition. Full article

Viscoelastic testing (VET) is widely used to guide hemostatic therapy in patients with coagulopathy. One important application is the detection of fibrinolysis, defined as a reduction in clot amplitude after maximum clot firmness (MCF), quantified as maximum lysis (ML). Low ML values have recently been associated with adverse outcomes in trauma and sepsis. However, the biological basis of low ML remains unclear. Objective: To determine whether low ML values reflect reduced plasmin-mediated fibrinolysis in tissue factor (TF) activated viscoelastic assays (EX-assay). Methods: A total of 120 healthy adults (52.5% female; mean age 38.2 ± 14.1 years) were studied. EX-assay without fibrinolysis inhibition were compared with assays containing the antifibrinolytic agent tranexamic acid (AP-assay). VET parameters obtained with and without fibrinolysis inhibition were compared using paired analyses, Pearson correlation, and Bland–Altman methods. Results: Clot firmness at 10 min (CA10) was similar with or without fibrinolysis inhibition; although MCF differed statistically, the difference was clinically negligible. ML ranged from 1% to 13% in both assays, with nearly identical mean values (5.9 ± 2.6% vs. 6.0 ± 2.6%). Correlation analysis demonstrated strong agreement for CA10, MCF, and ML between assays, and Bland–Altman analysis confirmed minimal bias for ML. Conclusions: Low ML values in TF-triggered viscoelastic assays were unaffected by tranexamic acid, suggesting that they are unlikely to reflect plasmin-mediated fibrinolysis. These findings support the contribution of alternative mechanisms, such as platelet-mediated clot retraction. Full article

In this article, we study the homotopy aspects of intersection graphs of topological semigroups. We begin by defining the top intersection graph $T{G}_{\mathbb{X}}$ and investigating how the algebraic and topological properties of a topological semigroup are reflected in the global structure of this graph. In particular, we characterize when $T{G}_{\mathbb{X}}$ is totally disconnected, bipartite, or planar in terms of the order and factorization of the underlying semigroup. We then introduce the notions of $HTG$-semigroups, graphical homomorphisms, and graphical homotopy relations, thereby developing a graphical homotopy framework. Within this setting, we study $Gr$-homotopy equivalences, $Gr$-contractible spaces, and retraction phenomena, including $DGr$-retracts and homotopy extension properties. Finally, we introduce graphical total semigroups and equip the set of $Gr$-path homotopy classes $\left[{\mathbb{X}}_{pe}\right]$ with a natural $\Delta$-uniform topology. We show that this topology is compatible with the induced semigroup operation, yielding a topological semigroup structure. Overall, this work provides a unified algebraic, topological, and graph-theoretic perspective, and opens the door to further applications of homotopy theory in the study of intersection graphs of topological semigroups. Full article

In this work, we construct a homotopy theory for a class of intersection graphs arising from topological monoids. We introduce the M-intersection graph of a ${\tau }_e$-monoid, where the vertices correspond to proper ${\tau }_e$-submonoids and adjacency is defined by trivial intersection. Several structural properties of the graph, including total disconnectedness, bipartiteness and planarity, are investigated and shown to be closely related to the algebraic structure and decomposition of finite ${\tau }_e$-monoids. Based on this framework, we develop a graphical homotopy theory by introducing graphical ${\tau }_e$-monoids, graphical homomorphisms, and graphical homotopies. We study graphical homotopy equivalence, graphical contractibility, and path monoids, and examine retraction properties through graphical retracts, D-graphical retracts and graphical homotopy extension properties. Furthermore, we present an example of graphical comprehensive monoids and construct a $\theta$-homogeneous topology on the set of graphical path homotopy classes. We show that this topology is compatible with the induced monoid operation, yielding a well-behaved functorial topological monoid structure. Full article

Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability. Full article

Background: Closing extraction spaces with clear aligners remains a significant biomechanical challenge, frequently involving difficulties in sagittal control, torque expression, and intra-arch anchorage. Although various sequential or phased retraction strategies exist, the Caterpillar Motion protocol has not yet been formally defined. This clinical report describes the Caterpillar Motion staging protocol and illustrates its application through representative extraction cases, rather than providing a systematic review or experimental comparison. Case Presentation: Two adult patients with extraction-based malocclusions were treated using the Caterpillar Motion staging protocol. Case 1 involved bimaxillary first-premolar extractions with maximum anchorage requirements and periodontal limitations in the mandibular incisors. Case 2 presented as a full Class II malocclusion requiring maxillary first-premolar extractions with moderate anchorage for sagittal camouflage. In both cases, tooth movement was organized into alternating functional groups, with waves limited to 2 mm of sagittal closure. Discussion: The Caterpillar Motion protocol reduces the risk of aligner bowing effect, increases effective crown engagement, and redistributes anchorage demands by preventing simultaneous shortening of both arch extremities. Both cases demonstrated controlled anterior retraction, stable posterior anchorage, and favorable root parallelism. Conclusions: Caterpillar Motion offers a biomechanically coherent and clinically reproducible staging strategy for clear aligner extraction therapy. Further controlled studies are needed to validate its advantages over traditional linear and en-masse protocols. Full article

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A₂ (TXA₂), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA₂-mediated signaling offers strong antithrombotic potential. TXA₂-antagonistic effects were evaluated using U46619, a stable TXA₂ analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ₃, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP₃RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ₃ and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA₂-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity. Full article

As biodiversity continues to decline under the combined pressures of climate change and urbanization, there is an urgent need for comprehensive risk assessment. Given the close interconnection between biodiversity and ecosystem functions, two major risk factors have been identified: (1) habitat loss (destruction) and (2) habitat gain expansion (disturbance). To address these challenges, this study proposes an integrated approach for biodiversity risk assessment that spatially and quantitatively evaluates risks from a holistic perspective. Specifically, an integrative modeling framework (BIOMOD2–LCM–MigClim) was developed to predict biodiversity patterns under the simultaneous impacts of climate change and urbanization. In parallel, novel indices, the Persistence Index (PI) and Disturbance Index (DI), were designed to assess biodiversity risks from multidimensional temporal and spatial perspectives. Based on the biodiversity risk types defined as Risk 1 (habitat loss; climate change risk species) and Risk 2 (habitat gain–expansion; invasive species), the study derived spatial distribution patterns and conducted a time series analysis of risk characteristics. Results highlight the dynamic ecological interactions in competitive areas, where Risk 2 advances by intruding into Risk 1 zones, thereby accelerating Risk 1 retraction. These findings confirm the need for integrated methodologies to capture shifting biodiversity responses and provide robust decision support for fundamental biodiversity policies. Full article

Background: Personalized medicine in breast cancer surgery aims to tailor therapeutic strategies not only to tumor biology but also to patient-specific risk factors and surgical outcomes. The Alexis^® retractor, originally designed for abdominal and pelvic surgery, may represent an innovative tool to optimize axillary surgical procedures in selected patients. Its atraumatic design and protective sheath provide enhanced visibility, minimized tissue trauma, and a potentially lower risk of postoperative complications, thus contributing to individualized surgical care. Methods: We conducted a retrospective, single-center study at Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2024 and April 2025. Patients undergoing breast-conserving surgery or mastectomy with axillary access were included. The Alexis^® retractor was used for axillary tissue retraction in procedures such as sentinel lymph node biopsy and axillary dissection. Outcomes were assessed at 7, 14, and 30 days postoperatively, with particular focus on complication rates and surgical efficiency. Results: Thirty-seven patients (38 procedures) were analyzed. Seromas occurred in four patients (10.8%) and were managed with ultrasound-guided aspiration. Wound dehiscence occurred in two patients (5.4%) and was treated with advanced dressings. No infections, hemorrhages, or flap necrosis were observed. No systemic complications occurred. Conclusions: The preliminary results suggest that the Alexis^® retractor may support a more personalized approach to axillary surgery in breast cancer, by reducing early postoperative complications and improving surgical ergonomics. Its atraumatic design and protective sheath may help tailor surgical management to individual patient risk profiles, minimizing tissue damage and infection risk while enhancing intraoperative visibility and efficiency. Further prospective, controlled studies with larger cohorts are needed to confirm its role in precision breast surgery and to define which patient subgroups may benefit the most. Full article

Vitiligo is a chronic autoimmune dermatosis defined by selective melanocyte depletion and patchy depigmentation. IFN–γ-driven recruitment of autoreactive CD8⁺ T cells and induction of melanocyte apoptosis are central to its pathogenesis. Current therapies—including UVB phototherapy, tacrolimus, vitamin D3 analogs, and surgical methods—show limited and inconsistent efficacy. Emerging treatments like JAK inhibitors and WNT activators offer potential but require further validation. Translational progress is hindered by a lack of scalable human models. Here, we describe a tunable in vitro vitiligo platform in which human iPSC-derived melanocytes (iMc) are co-cultured with keratinocytes on Matrigel and exposed to precise graded IFN-γ concentrations. Our data revealed dose-dependent decreases in iMc survival and dendritic structure, faithfully mirroring derived melanocyte pathology. Leveraging this platform, we first evaluated the short-term efficacy of the ROCK inhibitor Y27632 under early-stage patient IFN-γ concentrations representative of patient lesional thresholds. At three days, Y27632 significantly upregulated adhesion molecules E-cadherin and DDR1, and two central factors—ET1 and bFGF. Importantly, ROCK inhibition reversed dendritic retraction and improved overall viability of iMc-keratinocytes. These findings position ROCK blockade as a promising adjunctive strategy and establish a pre-clinical platform for evaluating combination therapies for durable pigment restoration. Full article

This study presented an autonomous shield-cutting end-effector for maize surrounding weeding (SEMSW), addressing the challenges of the low weed removal rate (WRR) and high seedling damage rate (SDR) in northern China’s 3–5 leaf stage maize. The SEMSW integrated seedling positioning, robotic arm control, and precision weeding functionalities: a seedling positioning sensor identified maize seedlings and weeds, guiding XYZ translational motions to align the robotic arm. The seedling-shielding anti-cutting mechanism (SAM) enclosed crop stems, while the contour-adaptive weeding mechanism (CWM) activated two-stage retractable blades (TRWBs) for inter/intra-row weeding operations. The following key design parameters were determined: 150 mm inner diameter for the seedling-shielding disc; 30 mm minimum inscribed-circle for retractable clamping units (RCUs); 40 mm ground clearance for SAM; 170 mm shielding height; and 100 mm minimum inscribed-circle diameter for the TRWB. Mathematical optimization defined the shape-following weeding cam (SWC) contour and TRWB dimensional chain. Kinematic/dynamic models were introduced alongside an adaptive sliding mode controller, ensuring lateral translation error convergence. A YOLOv8 model achieved 0.951 precision, 0.95 mAP50, and 0.819 mAP50-95, striking a balance between detection accuracy and localization precision. Field trials of the prototype showed 88.3% WRR and 2.2% SDR, meeting northern China’s agronomic standards. Full article

Background: Chronic postsurgical pain (CPSP) poses a major clinical challenge due to unresolved links between neurotrophic pathways and endoplasmic reticulum (ER) stress. While Neurotrophic Tyrosine Kinase Receptor Type 1 (NTRK1) modulates ER stress in neuropathic pain, its interaction with Insulin-Like Growth Factor II (IGF2) in CPSP remains uncharacterized, impeding targeted therapy. This study defined the spinal NTRK1-IGF2-ER stress axis in CPSP. Methods: Using a skin/muscle incision–retraction (SMIR) rat model, we integrated molecular analyses and intrathecal targeting of NTRK1 (GW441756) or IGF2 (siRNA). Results: SMIR surgery upregulated spinal NTRK1, IGF2, and ER stress mediators. NTRK1 inhibition reduced both NTRK1/IGF2 expression and ER stress, reversing mechanical allodynia. IGF2 silencing attenuated ER stress and pain but did not affect NTRK1, revealing a unidirectional signaling cascade where NTRK1 drives IGF2-dependent ER stress amplification. These findings expand understanding of stress-response networks in chronic pain. Conclusions: We show that spinal NTRK1 drives IGF2-mediated ER stress to sustain CPSP. The NTRK1-IGF2-ER stress axis represents a novel therapeutic target; NTRK1 inhibitors and IGF2 biologics offer non-opioid strategies for precision analgesia. This work advances CPSP management and demonstrates how decoding unidirectional signaling hierarchies can transform neurological disorder interventions. Full article

Background/Objectives: Spread through air spaces (STAS) is defined as the spread of tumor cells into the parenchymal alveolar space beyond the margins of the main tumor, and it is associated with worse clinical outcomes in resected lung adenocarcinoma. This study aimed to evaluate the preoperative computed tomography (CT) findings of primary lung adenocarcinoma in surgically resected T1 cases and to compare CT findings with and without STAS. Methods: A total of 145 patients were included in this study. The following factors were evaluated on CT images: nodule type (pure ground-glass nodule [GGN], part-solid nodule, or solid nodule), margin (smooth or irregular), the presence of lobulation, spicula, cavity, calcification, central low attenuation, peripheral opacity (well-defined or ill-defined), air bronchogram, satellite lesions, pleural retraction, pulmonary emphysema, and interstitial pneumonia; CT values (maximum, minimum, and mean); volume (tumor and solid component); and diameter (tumor and solid component). CT criteria were compared between the presence and absence of STAS. Results: Lobulation and central low attenuation were significantly more frequent in patients with STAS (p < 0.05). The mean CT value, and the volume, rate, and diameter of the solid component were significantly larger in cases with STAS (p < 0.05). A multiple logistic regression analysis identified central low attenuation as an indicator of the presence of STAS (p < 0.001; odds ratio, 3.993; 95% confidence interval, 1.993–8.001). Conclusions: Quantitative and qualitative analyses are useful for differentiating between the presence and absence of STAS. Full article