Search Results (718)

This paper proposes a novel sound source localization system that combines parametric homomorphic deconvolution with neural network regression to estimate the angle of arrival from a single-channel signal. The system uses an analog adder to sum signals from three spatially arranged microphones, reducing system hardware complexity and requiring the estimation of time delays from a single-channel signal. Time delay features are extracted through parametric homomorphic deconvolution methods—Yule–Walker, Prony, and Steiglitz–McBride—and input to multilayer perceptrons configured with various structures. Simulations confirm that Steiglitz–McBride provides the sharpest and most accurate predictions with reduced model order, while Yule–Walker shows slightly better performance than Prony at higher orders. A hybrid learning strategy that combines synthetic and real-world data improves generalization and robustness across all angles. Experimental validations in an anechoic chamber support the simulation results, showing high correlation and low deviation values, especially with the Steiglitz–McBride method. The proposed sound source localization system demonstrates a compact and scalable design suitable for real-time and resource-constrained applications and provides a promising platform for future extensions in complex environments and broader signal interpretation domains. Full article

Arginine vasotocin (AVT) is well known for its role in steroidogenesis and estradiol biosynthesis during early brain development in Epinephelus coioides. Despite its hormonal functions, the biological significance of AVT across different taxa remains poorly understood. Hence, the present study aims to unravel the evolutionary conservation and functional annotation of AVT in different taxa. Additionally, the antimicrobial properties of AVT were investigated across multiple conserved domains. From the sequence comparison results, AVT is highly conserved and a core motif across teleosts, mammals, plants, and bacteria, suggesting functional constraints under strong evolutionary selective pressure. Phylogenetic analyses highlighted AVT and its homologs evolved from a common ancestral gene. The functional enrichment analyses of the genes revealed different taxa that share an analogy with AVT genes. The major pathways for AVT and its homologs are identified in neuroendocrine, immune, and stress signaling. Importantly, a conserved AMP-like motif within the AVT sequence (GIRQCMSCGPGDRGR) was identified. The motif is predicted for its potential role in membrane permeabilization and antimicrobial defense. Physicochemical properties of this peptide showed cationic and amphipathic features, with cysteine residues conferring structural stability. Overall, the results underscore the pleiotropic role of AVT across different taxa, showing its evolutionary stability. AMP-like AVT motif was predicted as a promising candidate for synthetic peptide design. Experimental evaluation with peptides will determine their antimicrobial potential in infection models. Full article

Molecularly imprinted polymers (MIPs) have emerged as promising materials for selectively targeting biomolecules, including quorum sensing autoinducers that regulate bacterial communication and biofilm formation. In this study, both single-template and dual-template strategies were employed to design and synthesize MIPs capable of capturing autoinducer-2 analogs using (3R,4S)-tetrahydro-3,4-furandiol (T1) or (R/S) 2,2-dimethyl-1,3-dioxolane-4-methanol (T2) as the templates. This approach offers translational potential of a complementary or non-antibiotic strategy to conventional antimicrobial therapies in mitigating biofilm-associated infections. Computational modeling guided the rational selection of functional monomers, predicting favorable interaction energies (ΔE_C up to −135 kcal·mol⁻¹) and optimal hydrogen-bonding patterns to enhance template–polymer affinity. The synthesized MIPs were characterized using spectroscopic and microscopic techniques to confirm imprinting efficiency and structural integrity. The adsorption capacity measurements demonstrated higher adsorption capacity and selectivity of MIPs compared to non-imprinted polymers, with the highest selectivity equal to 3.36 for T1 and 3.14 for T2 on MIPs fabricated from methacrylic acid. Preliminary microbiological evaluations using Chromobacterium violaceum ATCC 12472 reveal that the MIPs prepared from 2-hydroxyethyl methacrylate effectively inhibited violacein production by up to 78.2% at 5.0 mg·mL⁻¹, consistent with quorum sensing interference. These findings highlight the feasibility of employing molecular imprinting to target autoinducer-2 analogs, introducing a novel synthetic strategy for disrupting bacterial communication. This further suggests that molecular imprinting can be leveraged to develop potent quorum-sensing inhibitors, an approach that offers translational potential as an alternative to conventional antimicrobial strategies to mitigate biofilm-associated infections. Full article

Lipoxins were discovered 40 years ago, and since then, their beneficial roles for human health have been confirmed in numerous studies. These small molecules belong to the eicosanoid class of compounds, which are generated metabolically by lipoxygenases. Lipoxins are released during various diseases and conditions, including but not limited to systemic inflammation, infection, asthma, cancer, diabetes, and cardiovascular disorders. Recently, several synthetic lipoxin analogs have been developed that also exhibit potent anti-inflammatory properties. In this review, we discuss the inflammation-resolving roles of lipoxins in various major diseases. Further, we summarize the latest reports on the use of synthetic lipoxins as potential therapeutic agents and discuss the role of aspirin-dependent lipoxin production in alleviating various diseases, including cancer. Full article

Background/Objectives: Oxytocin as well as carbetocin, a synthetic analog of oxytocin with a longer duration of action, can affect the cardiovascular system, which can be recorded in electrocardiographic Holter recordings. The choice of the appropriate dose of oxytocin or carbetocin should take into account potential cardiovascular effects. Methods: A total of 70 pregnant women who previously qualified for elective cesarean section and enrolled in the study were divided into two groups. The oxytocin group (OXY) received 5 IU of oxytocin intravenously (i.v.). The carbetocin group (CARBE) received 100 µg of carbetocin intravenously. Both drugs were used alternatively to contract the uterine muscle. Continuous Holter electrocardiograph recording started 30 min before the procedure and continued until about 3 h after the procedure. Results: No abnormalities were observed in either of the analyzed groups during intraoperative ECG recordings at either the highest or lowest recorded heart rate values. The incidence of ST-segment-lowering episodes, the depth of the denivelation and its duration did not differ between the groups studied. The incidence of additional ventricular beats was comparable in the OXY and CARBE groups, both before and after the administration of uterotonic drugs. In the CARBE group, no significant changes in MAP were recorded during the entire ST-segment-lowering period. Analysis of heart rate changes during ST lowering showed no differences between the study groups. Conclusions: A thorough analysis of perioperative ECG recordings revealed no significant alterations in ECG patterns, neither in response to oxytocin nor carbetocin administration during cesarean sections. Full article

As artificial intelligence (AI) systems attain greater autonomy, recursive reasoning capabilities, and complex environmental interactions, they begin to exhibit behavioral anomalies that, by analogy, resemble psychopathologies observed in humans. This paper introduces Psychopathia Machinalis: a conceptual framework for a preliminary synthetic nosology within machine psychology intended to categorize and interpret such maladaptive AI behaviors. Drawing structural inspiration from psychiatric diagnostic manuals, we propose a taxonomy of 32 AI dysfunctions encompassing epistemic failures, cognitive impairments, alignment divergences, ontological disturbances, tool and interface breakdowns, memetic pathologies, and revaluation dysfunctions. Each syndrome is articulated with descriptive features, diagnostic criteria, presumed AI-specific etiologies, human analogs (for metaphorical clarity), and potential mitigation strategies. This framework is offered as an analogical instrument—eschewing claims of literal psychopathology or consciousness in AI, yet providing a structured vocabulary to support the systematic analysis, anticipation, and mitigation of complex AI failure modes. Drawing on insights from psychiatric classification, cognitive science, and philosophy of mind, we examine how disordered AI behaviors may emerge from training instabilities, alignment conflicts, or architectural fragmentation. We argue that adopting an applied robopsychological perspective within a nascent domain of machine psychology can strengthen AI safety engineering, improve interpretability, and contribute to the design of more robust and reliable synthetic minds. Full article

Silicon has a striking similarity to carbon and is found in plant cells. However, there is no specific role that has been assigned to silicon in the life cycle of plants. The amount of silicon in plant cells is species specific and can reach levels comparable to macronutrients. Silicon is used extensively in artificial intelligence, nanotechnology, and the digital revolution, and thus can serve as an informational molecule such as nucleic acids. The diverse potential of silicon to bond with different chemical species is analogous to carbon; thus, it can serve as a structural candidate similar to proteins. The discovery of large amounts of silicon on Mars and the moon, along with the recent development of enzyme that can incorporate silicon into organic molecules, has propelled the theory of creating silicon-based life. The bacterial cytochrome has been modified through directed evolution such that it could cleave silicon–carbon bonds in organo-silicon compounds. This consolidates the idea of utilizing silicon in biomolecules. In this article, the potential of silicon-based life forms has been hypothesized, along with the reasoning that autotrophic virus-like particles could be used to investigate such potential. Such investigations in the field of synthetic biology and astrobiology will have corollary benefits for Earth in the areas of medicine, sustainable agriculture, and environmental sustainability. Full article

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

The increasing complexity and scale of electronic health records (EHRs) demand advanced tools for efficient data retrieval, summarization, and comparative analysis in clinical practice. MERA (Medical Electronic Records Assistant) is a Retrieval-Augmented Generation (RAG)-based AI system that addresses these needs by integrating domain-specific retrieval with large language models (LLMs) to deliver robust question answering, similarity search, and report summarization functionalities. MERA is designed to overcome key limitations of conventional LLMs in healthcare, such as hallucinations, outdated knowledge, and limited explainability. To ensure both privacy compliance and model robustness, we constructed a large synthetic dataset using state-of-the-art LLMs, including Mistral v0.3, Qwen 2.5, and Llama 3, and further validated MERA on de-identified real-world EHRs from the MIMIC-IV-Note dataset. Comprehensive evaluation demonstrates MERA’s high accuracy in medical question answering (correctness: 0.91; relevance: 0.98; groundedness: 0.89; retrieval relevance: 0.92), strong summarization performance (ROUGE-1 F1-score: 0.70; Jaccard similarity: 0.73), and effective similarity search (METEOR: 0.7–1.0 across diagnoses), with consistent results on real EHRs. The similarity search module empowers clinicians to efficiently identify and compare analogous patient cases, supporting differential diagnosis and personalized treatment planning. By generating concise, contextually relevant, and explainable insights, MERA reduces clinician workload and enhances decision-making. To our knowledge, this is the first system to integrate clinical question answering, summarization, and similarity search within a unified RAG-based framework. Full article

As the most unstable crystalline form of calcium carbonate, vaterite is rarely found in nature due to being highly prone to phase transitions. However, its high specific surface area, excellent biocompatibility, and high solubility properties have led to a research boom and the following breakthroughs in the last two decades: (1) From primitive calculations and spectroscopic analyses to modern multidimensional research methods combining calculations and experiments, the crystal structure of vaterite has turned from early identifications in orthorhombic and hexagonal crystal systems to a complex polymorphic structure within the monoclinic crystal system. (2) The formation process of vaterite not only conforms to the classical crystal growth theory but also encompasses the nanoparticle aggregation theory, which incorporates the concepts of oriented nanoparticle assembly and mesoscale transformation. (3) Regardless of the conditions, the formation of vaterite depends on an excess of CO₃²⁻ relative to Ca²⁺, and its stability duration relates to preservation conditions. (4) Vaterite demonstrates significant value in biomedical applications—including bone repair scaffolds, targeted drug carriers, and antibacterial coating materials—leveraging its porous structure, high specific surface area, and exceptional biocompatibility. While it also shows utility in environmental pollutant adsorption and general coating technologies, the current research remains predominantly concentrated on its medical applications. Currently, the rapid transformation of vaterite presents the primary limitation for its industrial application. Future research should prioritize investigating its formation kinetics and stability. Full article

In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with R_f and R_r exceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH⁻) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds. Full article

A new, simple machine was developed to address a long-standing challenge in biomedical and mechanical engineering: how to enhance the primary stability and long-term integration of screws and implants in low-density or heterogeneous materials, such as bone or composite substrates. Traditional screws often rely solely on external threading for fixation, leading to limited cohesion, poor integration, or early loosening under cyclic loading. In response to this problem, we designed and built a novel device that leverages a unique mechanical principle to simultaneously perforate, collect, and compact the substrate material during insertion. This mechanism results in an internal material interlock, enhancing cohesion and stability. Drawing upon principles from physics, chemistry, engineering, and biology, we evaluated its biomechanical behavior in synthetic bone analogs. The maximum insertion (MIT) and removal torques (MRT) were measured on synthetic osteoporotic bones using a digital torquemeter, and the values were compared directly. Experimental results demonstrated that removal torque (mean of 21.2 Ncm) consistently exceeded insertion torque (mean of 20.2 Ncm), indicating effective material interlocking and cohesive stabilization. This paper reviews the relevant literature, presents new data, and discusses potential applications in civil infrastructure, aerospace, and energy systems where substrate cohesion is critical. The findings suggest that this new simple machine offers a transformative approach to improving fixation and integration across multiple domains. Full article

Post-traumatic stress disorder (PTSD) has traditionally been viewed as a psychiatric disorder of fear, memory, and emotional regulation. However, growing evidence implicates systemic and neuroinflammation as key contributors. Individuals with PTSD often exhibit elevated blood levels of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and C-reactive protein, indicating immune dysregulation. Dysfunctions in the hypothalamic–pituitary–adrenal (HPA) axis marked by reduced cortisol levels impair the body’s ability to regulate inflammation, allowing persistent immune activation. Circulating cytokines cross a weakened blood–brain barrier and activate microglia, which release additional inflammatory mediators. This neuroinflammatory loop can damage brain circuits critical to emotion processing including the hippocampus, amygdala, and prefrontal cortex, and disrupt neurotransmitter systems like serotonin and glutamate, potentially explaining PTSD symptoms such as hyperarousal and persistent fear memories. Rodent models of PTSD show similar inflammatory profiles, reinforcing the role of neuroinflammation in disease pathology. Bromo-epi-androsterone (BEA), a synthetic analog of dehydroepiandrosterone (DHEA), has shown potent anti-inflammatory effects in clinical trials, significantly reducing IL-1β, IL-6, and TNF-α. By modulating immune activity, BEA represents a promising candidate for mitigating neuroinflammation and its downstream effects in PTSD. These findings support the rationale for initiating clinical trials of BEA as a novel therapeutic intervention for PTSD. Full article

During the Swern oxidation of 3-methylbut-3-en-1-ol, an unexpected C-C bond formation product, 3-methyl-2-(methylthio)but-2-enal, was obtained. Its structure was characterized using ¹H-NMR, ¹³C-NMR, and HRMS. Based on the classical Swern oxidation mechanism and the unique structural features of the substrate, we propose a plausible reaction pathway. This discovery not only provides insights into the selection of oxidation conditions for 1, 1-disubstituted homoallylic alcohols with analogous structures but also offers a viable synthetic route for the preparation of compounds containing the 3-methyl-2-(methylthio)but-2-enal motif. Full article

The efficient synthetic routes and evaluates cytotoxic profiles of denitroaristolochic acids II–V (DAA-II–V) were demonstrated in this study. Based on retrosynthetic analysis, a modular synthetic strategy was developed through Suzuki–Miyaura coupling, Wittig reaction, and bismuth triflate-catalyzed intramolecular Friedel–Crafts cyclization to efficiently construct the phenanthrene core. Process optimization significantly improved yields: aryl bromide intermediate A reached 50.8% yield via bromination refinement, while arylboronic ester intermediate B overcame selectivity limitations. Combining Darzens condensation with Wittig reaction enhanced throughput, achieving 88.4% yield in the key cyclization. Structures were confirmed by NMR and mass spectra. CCK-8 cytotoxicity assays in human renal proximal tubular epithelial cells revealed distinct toxicological profiles: DAA-III and DAA-IV exhibited IC₅₀ values of 371 μM and 515 μM, respectively, significantly higher than the nitro-containing prototype AA-I (270 μM), indicating that the absence of nitro group attenuates but does not eliminate toxicity, potentially via altered metabolic activation. DAA-II and DAA-V showed no detectable cytotoxicity within assay limits, suggesting reduced toxicological impact. Structure–activity analysis exhibited that the nitro group is not essential for cytotoxicity, with methoxy substituents exerting limited influence on potency. This challenges the conventional DNA adduct-dependent toxicity paradigm, implying alternative mechanisms like oxidative stress or mitochondrial dysfunction may mediate damage in denitro derivatives. These systematic findings provide new perspectives for AA analog research and a foundation for the rational use and safety assessment of Aristolochiaceae plants. Full article