Search Results (276)

This paper critiques Hava Tirosh-Samuelson’s view of transhumanism as techno-idolatry by applying Derrida’s notion of the unconditional “to-come” and the generalized fetish. While acknowledging Tirosh-Samuelson’s stance that fetishes should not be reduced to idols, I argue that she fails to extend this understanding to transhumanism, instead depicting its fetishes as fixed idols. Drawing on Derrida’s notion of the generalized fetish, I argue that religious objects in Judaism (like the shofar or tefillin) function not as objects of worship but as material mediators of divine relation—tangible signs that carry symbolic, spiritual, and covenantal meaning while gesturing toward the divine without claiming to contain or represent it. Similarly, in transhumanism, brain-computer interfaces and AI act as fetishes that extend human capability and potential while remaining open to future reinterpretation. These fetishes, reflecting Derrida’s idea of the unconditional “to-come,” resist closure and allow for ongoing change and reinterpretation. By reducing transhumanism to mere idolatry, Tirosh-Samuelson overlooks how technological fetishes function as dynamic supplements, open to future possibilities and ongoing reinterpretation, which can be both beneficial and harmful to humanity now and in the future. Full article

Pharmaceuticals are increasingly being detected in coastal ecosystems globally, but contamination and bioaccumulation levels are understudied in temporarily closed estuaries. In these systems, limited freshwater inputs and periodic closure may predispose them to pharmaceutical accumulation. We quantified in situ water column pharmaceutical levels at five sites in a temporarily closed model urban estuary (Zandvlei Estuary) in Cape Town, South Africa, that has been heavily anthropogenically modified. The results indicate an almost 100-fold greater concentration of pharmaceuticals in the estuary relative to False Bay, into which the estuary discharges, with acetaminophen (max: 2.531 µg/L) and sulfamethoxazole (max: 0.138 µg/L) being the primary pollutants. Acetaminophen was potentially bioaccumulative, while nevirapine, carbamazepine and sulfamethoxazole were bioaccumulated (BAF > 5000 L/kg) by sandprawns (Kraussillichirus kraussi), which are key coastal endobenthic ecosystem engineers in southern Africa. The assimilative capacity of temporarily closed estuarine environments may be adversely impacted by wastewater discharges that contain diverse pharmaceuticals, based upon the high bioaccumulation detected in key benthic engineers. Full article

Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. Full article

Anthyllis vulneraria is a traditional medicinal plant with confirmed anti-inflammatory properties, attributed to its high polyphenolic content. This study aimed to evaluate the wound-healing potential of A. vulneraria leaf extract in a rat burn model. Four groups of eight Wistar rats each received the following daily topical applications for 14 days: vehicle cream (negative control); silver sulfadiazine (positive control); or plant-based creams containing either 1 mg/cm² or 2 mg/cm² of polyphenols (experimental groups 1 and 2, respectively). On days 7 and 14, four animals per group were euthanized for histological and oxidative stress evaluations. LC-MS/MS analysis of the leaf extract identified hyperoside, ferulic acid, and p-coumaric acid as major constituents. Experimental group 1 showed significantly enhanced wound closure on days 5 and 7, while group 2 exhibited a significant effect on day 5. All oxidative stress markers, except catalase activity, differed significantly among the groups, with the most favorable results observed in group 2. IL-8 levels decreased after the extract treatment, while no significant microscopic changes were observed. These results indicate that A. vulneraria leaf extract may serve as a valuable adjuvant in burn wound healing. Full article

Background/Objectives: Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P)—a common and highly heritable birth defect with a multifactorial etiology. Methods: To identify new risk loci, we conducted a genome-wide gene–environment interaction (GEI) analysis of CL/P with maternal smoking and vitamin use in Filipinos (N_cases = 540, N_controls = 260). Since GEI analyses are typically low in power and the results can be difficult to interpret, we applied multiple testing frameworks to evaluate potential GEI effects: a one degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. Results: While no genome-wide significant interactions were detected, we identified 11 suggestive GEIs with smoking and 24 with vitamin use. Several implicated loci contain biologically plausible genes. Notable interactions with smoking include loci near FEZF1, TWIST2, and NET1. While FEZF1 is involved in early neuronal development, TWIST2 and NET1 regulate epithelial–mesenchymal transition, which is required for proper lip and palate fusion. Interactions with vitamins encompass CECR2—a chromatin remodeling protein required for neural tube closure—and FURIN, a critical protease during early embryogenesis that activates various growth factors and extracellular matrix proteins. The activity of both proteins is influenced by folic acid. Conclusions: Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics. Full article

Silk fibroin has recently gained considerable attention as a promising biomaterial for use in medical and bioengineering technologies due to its biocompatibility and favorable mechanical properties. In this study, composite gel based on silk fibroin microparticles and carboxymethyl cellulose was developed, characterized by a viscous, homogeneous white mass containing uniformly distributed fibroin microparticles ranging from 1 to 20 μm in size. The gel exhibited a kinematic viscosity of 36.5 × 10⁻⁶ St, allowing for convenient application to wounds using a syringe or spatula while preventing uncontrolled spreading. The cytocompatibility of the gel was confirmed using the methylthiazol tetrazolium (MTT) assay, which showed no cytotoxic effects on 3T3 fibroblast cells. Furthermore, the gel remained stable for over one year when stored at 10 °C, in contrast to conventional fibroin solutions, which typically lose stability within a month under similar conditions. In a full-thickness skin wound model in rats, the application of the gel significantly accelerated skin regeneration, with complete wound closure observed by day 15, compared with 30 days in the control group. Histological analysis confirmed the restoration of all skin layers. These findings demonstrate the high potential of the gel for applications in regenerative medicine and tissue engineering. Full article

Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes. Full article

Naturally occurring antioxidants have attracted significant research interest, owing to their radical scavenging ability that can be improved via structural modifications. In this study, aromaticity-extended resveratrol analogues (3–5) containing chalcogens were designed and synthesized using ring closure and Horner–Wadsworth–Emmons reactions. The antioxidant activities of the derivatives were evaluated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABST) assay. All resveratrol derivatives (3–5) exhibited higher radical scavenging activities than resveratrol 1 and analogue 2, with benzoselenophene-conjugated derivative 5 demonstrating the highest activity. The improved antioxidant performance of the resveratrol derivatives was attributed to the extended π conjugation resulting from the incorporation of fused rings, benzoheteroles. Additionally, the integration of benzoheteroles into resveratrol contributed to an efficient reduction in HOMO-LUMO gaps. This study demonstrates that aromaticity extension by introducing benzofuran, benzothiophene, and benzoselenophene is a feasible strategy for improving the antioxidant activity of naturally occurring oxidants. Full article

Carbon Capture and Storage (CCS) is a critical strategy for reducing CO₂ emissions from hard-to-abate sectors. Reliable and efficient reservoir simulation tools are essential for supporting the safe and effective deployment of CCS projects. This study presents a twofold contribution to CCS modeling in saline aquifers: (1) the validation of the Black Oil Model (BoM) as a computationally efficient alternative to compositional simulators, and (2) a systematic assessment of the impact of grid resolution on plume prediction accuracy. The BoM was benchmarked against three commercial compositional simulators—Eclipse E300, CMG-GEM, and TNavigator. The comparison focused on key aspects of CO₂ storage operations, including plume evolution to assess containment and storage security, as well as injection safety and efficiency through pressure and saturation profile analysis, evaluated across both the injection and the post-closure monitoring phases. The BoM successfully reproduced plume extent and CO₂ saturation distributions, with mean deviations of 3% during injection, 5% during post-closure, and an overall average of 4% across the entire project duration. Additionally, simulation times were reduced by a factor of four compared to compositional models. These results confirm the BoM’s practical utility as a robust and efficient tool for CO₂ storage simulation. In parallel, the study investigated the influence of vertical and lateral grid resolutions/coarsening on the accuracy of CO₂ modeling. Seven models were developed and evaluated using a hybrid qualitative–quantitative framework, consistent with the BoM validation methodology. Vertical resolution was found to be particularly critical during the monitoring phase. While a 5 m resolution proved adequate during injection, deviations in plume shape and magnitude during post-injection increased to an average of 15% compared to a fine 2 m vertical resolution model, highlighting the necessity of fine vertical discretization (≤2 m) to capture gravity-driven plume dynamics during the monitoring phase. Conversely, lateral grid resolution had a stronger effect during the injection phase. A lateral cell size of 150 m was required for accurate plume prediction, with 200 m remaining moderately acceptable for early-phase assessment and prospect ranking, whereas coarser lateral grids led to significant underestimation of plume spread and dissolution extent. These findings demonstrate that the BoM, when combined with informed grid resolution strategies, enables accurate and computationally efficient simulation of CO₂ storage in saline aquifers. The study provides practical guidelines for fluid model selection and spatial discretization, offering critical input to subsurface experts involved in CCS project development, monitoring design, and regulatory compliance. Full article

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth (EOB) phenotype due to disrupted MAPK signaling, abnormal epithelial differentiation, and morphogenesis. To further explore the roles of MAP3K1 in ocular development, we generated a Cre-inducible gain-of-function transgenic mouse, designated as Map3k1^TG, and crossed it with Lens epithelial (Le)-Cre mice to drive MAP3K1 overexpression in developing ocular surface epithelium (OSE). Map3k1^TG;Le-Cre embryos exhibited ocular defects including premature eyelid closure, lens degeneration, and corneal edema. While corneal epithelial differentiation remained intact, the lens epithelium degenerated with lens formation compromised. Eyelid epithelium was markedly thickened, containing cells with aberrant keratin (K)14/K10 co-expression. Genetic rescue experiments revealed that Map3k1^TG;Le-Cre restored eyelid closure in Map3k1 knockout mice, whereas MAP3K1 deficiency attenuated the epithelial thickening caused by transgene expression. Mechanistically, MAP3K1 overexpression enhanced c-Jun phosphorylation in vivo and activated JNK-c-Jun, WNT, TGFβ, and Notch signaling and promoted keratinocyte proliferation and migration in vitro. These findings highlight a dose-sensitive role for MAP3K1 in regulating epithelial proliferation, differentiation, and morphogenesis during eyelid development. Full article

This article contains a synthetic proof of the following proposition: consider a conic $c_1$ and its variable chord $AB$, which subtends a right angle at a given point P. Then, the foot E of the perpendicular dropped from P onto the line $AB$ lies on a certain circle (the line being the limiting case of the circle). To prove this proposition, we show how Poncelet’s closure theorem for quadrilaterals can be derived by elementary projective considerations only (without any computations, either in Cartesian or projective coordinates). Finally, the limiting case of the proposition, where the point P lies on the conic, is also mentioned. The problem can then be reduced to Frégier’s theorem and may represent a slightly different perspective on this theorem. Full article

STRAP (serine-threonine kinase receptor-associated protein), a WD domain-containing 38.5 kDa protein, was first identified in TGF-ß signaling and participates in scaffold formation in numerous cellular multiprotein complexes. It is involved in the regulation of several oncogenic biological processes, including cell proliferation, apoptosis, migration/invasion, tumor initiation and progression, and metastasis. STRAP upregulation in epithelial tumors regulates several signaling pathways, such as TGF-ß, MEK/ERK, Wnt/β-Catenin, Notch, PI3K, NF-κB, and ASK-1 in human cancers, including colon, breast, lung, osteosarcoma, and neuroblastoma. The upregulation of STRAP expression is correlated with worse survival in colorectal cancer following post-adjuvant therapy. Strap knockout sensitizes colon tumors to chemotherapy, delays APC-induced tumor progression, and reduces cancer cell stemness. The loss of Strap disrupts lineage differentiation, delays neural tube closure, and alters exon skipping, resulting in early embryonic lethality in mice. Collectively, the purpose of this review is to update and describe the diversity of targets functionally interacting with STRAP and to rationalize the involvement of STRAP in a variety of signaling pathways and biological processes. Therefore, these in vitro and in vivo studies provide a proof of concept that lowering STRAP expression in solid tumors decreases tumorigenicity and metastasis, and targeting STRAP provides strong translational potential to develop pre-therapeutic leads. Full article

Optimizing airflow organization is essential for ensuring the energy-efficient and secure operation of data centers. To address common airflow distribution issues in air-cooled systems, such as uneven air supply and cooling capacity imbalance, this study investigates a bidirectional airflow data center room located in a hot-summer and warm-winter region. A computational fluid dynamics (CFD) model was developed based on field-measured data to analyze the airflow distribution characteristics and evaluate the existing thermal conditions. Three optimization strategies were systematically examined: (1) Installation of rack blanking panels, (2) cold aisle containment with varying degrees of closure, and (3) combined implementations of these measures. Performance evaluation was conducted using three thermal metrics: the Return Temperature Index (RTI), Supply Heat Index (SHI), and Rack Cooling Index (RCIHI). The results demonstrate that among individual optimization strategies, rack blanking panels achieved the most significant improvement, reducing SHI by 42.61% while effectively eliminating local hotspots. For combined optimization strategies, the rack blanking panels and fully contained cold aisle containment showed optimal performance, improving cooling utilization efficiency by 88.26%. The optimal retrofit solution for this data center is the rack blanking panels with fully contained cold aisle containment. When considering budget constraints, the secondary option would be rack blanking panels with cold aisle top-only containment. These findings provide practical guidance for energy efficiency improvements in similar data center environments. Full article

Fractures and voids are widely distributed in slope rock masses. These defects promote crack initiation and propagation, ultimately leading to rock mass failure. Investigating their damage evolution mechanisms and strength characteristics is of significant importance for slope hazard prevention. A numerical simulation study of Brazilian splitting tests on disk samples containing prefabricated holes and fractures was conducted using the Finite Element Method with Cohesive Zone Modeling (FEM-CZM) in ABAQUS by embedding zero-thickness cohesive elements within the finite element model. This 2021 study analyzed the effects of fracture angle and length on tensile strength and crack propagation characteristics. The results revealed that when the fracture angle is small, cracks initiate near the fracture and propagate and intersect radially as the load increases, ultimately leading to specimen failure, with the crack coalescence pattern exhibiting local closure. As the fracture angle increases, the initiation location of the crack shifts. With an increase in fracture length, the crack initiation position may transfer to other parts of the fracture or near the hole, and longer fractures may result in more complex coalescence patterns and local closure phenomena. During the tensile and stable failure stages, the load–displacement curves of samples with different fracture angles and lengths exhibit similar trends. However, the fracture angle has a notable impact on the curve during the shear failure stage, while the fracture length significantly affects the peak value of the curve. Furthermore, as displacement increases, the proportion of tensile failure undergoes a process of rapid decline, slow rise, and then rapid decline again before stabilizing, with the fracture angle having a significant influence on the proportion of tensile failure. Lastly, as the fracture angle and length increase, the number of damaged cohesive elements shows an upward trend. This study provides novel perspectives on the tensile behavior of fractured rock masses through the FEM-CZM approach, contributing to a fundamental understanding of the strength characteristics and crack initiation mechanism of rocks under tensile loading conditions. Full article

Background/Objectives: Periodontal disease involves chronic immunoinflammatory processes and microbial dysbiosis, making phytochemicals with anti-inflammatory properties potential therapeutic agents. This study aimed to assess the modulatory effects of yellow passion fruit bagasse extract (PFBE) on periodontal cells under microbial condition. Methods: A human periodontal ligament (PDL) cell line was exposed to F. nucleatum ATCC 25586 to simulate a microbial environment in vitro in the presence and absence of PFBE containing three different concentrations (0.25, 0.50, and 1.00 µg/mL) of piceatannol. Pro-inflammatory markers (TNF-α, IL-8, CCL2), the antioxidant enzyme SOD2, and the protease marker MMP-1 were analyzed by real-time PCR. Protein levels were assessed via ELISA and NF-κB nuclear translocation by immunofluorescence. Cell viability was investigated using live/dead and alamarBlue assays, and in vitro wound healing was evaluated by an automated scratch assay. Results: PDL cells exposed to F. nucleatum significantly increased the gene and protein expression of all inflammatory markers. The stimulatory effects of F. nucleatum were significantly reduced when PDL cells were simultaneously exposed to PFBE. F. nucleatum triggered the NF-κB nuclear translocation while PFBE abrogated the F. nucleatum-stimulated NF-κB nuclear translocation at 60 min. Viability assays demonstrated that neither PFBE nor F. nucleatum were toxic or significantly affected PDL cell viability. In vitro wound closure was improved by the addition of PFBE to F. nucleatum. Conclusions: PFBE exhibited anti-inflammatory and anti-proteolytic effects while improving in vitro wound healing, suggesting a potential modulatory role of PFBE in periodontal disease prevention and treatment. Full article