Search Results (711)

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 MERA is designed to overcome key limitations of conventional LLMs in healthcare, such as hallucinations, outdated knowledge, and limited explainability.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

Despite advances in automation, the global manufacturing sector continues to rely heavily on manual package inspection, creating bottlenecks in production and increasing labor demands. Although disruptive technologies such as big data analytics, smart sensors, and machine learning have revolutionized industrial connectivity and strategic decision-making, real-time quality control (QC) on conveyor lines remains predominantly analog. This study proposes an intelligent package integrity monitoring system that integrates waste reduction strategies with both narrow and Generative AI approaches. Narrow AI models were deployed to detect package damage at full line speed, aiming to minimize manual intervention and reduce waste. Using a synthetically generated dataset of 200 paired top-and-side package images, we developed and evaluated 10 distinct detection pipelines combining various algorithms, image enhancements, model architectures, and data processing strategies. Several pipeline variants demonstrated high accuracy, precision, and recall, particularly those utilizing a YOLO v8 segmentation model. Notably, targeted preprocessing increased top-view MobileNetV2 accuracy from chance to 67.5%, advanced feature extractors with full enhancements achieved 77.5%, and a segmentation-based ensemble with feature extraction and binary classification reached 92.5% accuracy. These results underscore the feasibility of deploying AI-driven, real-time QC systems for sustainable and efficient manufacturing operations. Full article

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A₂-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides’ dual role in cytotoxicity and immunomodulation, ilimaquinone’s induction of the DNA damage response, and Aplidin’s disruption of protein synthesis via eEF1A2 binding. Pharmacokinetic challenges and structure–activity relationships are critically analyzed, emphasizing nanodelivery systems and synthetic analog development. This review bridges mechanistic insights with translational potential, offering a cohesive framework for future drug development. Full article

Background: Among the alkaloids from Cassia siamea, cassiarin A has outstanding antiprotozoal activity, but structure–activity relationships for this chemotype were only poorly understood until now. Methods: We worked out efficient approaches to hitherto underexplored analogs (12 examples) on three synthesis routes which mainly comprised variations in the methyl groups at C-2 and C-5. The new compounds were tested for antiprotozoal and cytotoxic activities. Results: Introduction of a (substituted) benzene ring at C-2 led to a significant enhancement of activity against Plasmodium falciparum, while modifications of the methyl group at C-5 and the phenolic group had detrimental effects. Two of the 2-phenyl analogs further showed a resistance index comparable to the one of the reference drug chloroquine. Although the novel derivatives did not show hemolytic effects, investigation on human endothelial (HUVEC) cells at relevant concentrations indicated strong cytotoxic effects on human cells. Conclusions: Systematic structure modifications of cassiarin A led to a significant enhancement of antiplasmodial activity, but the observed strong cytotoxicity to human cells renders this library of cassiarin A derivatives inadequate for drug development. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

N,N,N′-tris(trimethylsilyl)-carboximidamides are effective reagents in synthetic chemistry in reactions with both non-metal and metal halides, because the side product is the mild and volatile ClSi(CH₃)₃ rather than corrosive HCl. The title compound inserts the 2-pyridylamidinate fragment into several non-metal systems, including custom chelating radical ligands. The single-crystal X-ray diffraction structure was determined and modeled by Hirshfeld atom refinement using custom aspherical atomic scattering factors. Excellent data quality led to a model with enhanced precision of all interatomic distances and free refinement of H-atom positions and anisotropic displacement ellipsoids. This structure model is compared to the four previously published analogous structures. Full article

Metal–organic frameworks (MOFs) are a novel type of porous crystalline materials assembled from metal ions and organic linkers. Their derivatives can inherit characteristics such as high specific surface area, tunable porosity, and unique topological structures, which make MOF-derived metal oxides ideal catalysts for the selective catalytic reduction (SCR) of NO_x. This review focuses on the synthetic strategies of MOF-derived metal oxides and the latest progress of oxides derived from various typical MOFs materials (including MILs, ZIFs, UiO, BTC series, MOF-74, MOF-5, and Prussian blue analogs, etc.) in the catalytic reduction in NO_x, and analyzes the mechanisms for the enhanced catalytic performance. In addition, the challenges and prospects of MOF derivatives in catalytic applications are discussed. It is hoped that this review will help researchers understand the latest research progress of MOF-derived metal oxide materials in the catalytic removal of NO_x pollution. Full article

This study describes the synthesis of a series of dideaza analogs of methotrexate and their preliminary pharmacological and metabolic evaluation. The 5,8-dideazamethotrexate was efficiently obtained in five steps using a new synthetic route. Oxygenated and thiolated analogs of dideazamethotrexate were prepared following the devised pathway. Their cytotoxicity was studied in the A549 lung cancer cell line, as well as their DHFR dihydrofolate reductase inhibition activity and in vitro metabolism. The two new analogs showed strong activity on cancer cells and the enzymatic target. These compounds were not metabolized, a clear advantage over methotrexate, which is rapidly converted to the toxic metabolite 7-hydroxymethotrexate. Full article