Search Results (17,419)

Hydrophobicity has limited the efficiency of many drugs. To improve this, gold–silver alloy nanocomposites covered with carbon-based quantum dots were synthesized as a platform to reduce the drugs’ hydrophobicity. Using the hydrophobic drug Andrographolide as a model, it was demonstrated that these nanocomposites can decrease Andrographolide’s hydrophobicity (Log P from 2.632 to 0.56) without encapsulating the drug. Entry within prostate cancer (PC-3) cells and in vitro localization of the nanocomposites and Andrographolide was observed qualitatively via confocal microscopy and their identity confirmed by SERS inside the PC-3 cells. MTS assays demonstrated the carbon-based quantum dot layer covering the metal core of the nanocomposites stabilizes the oxidation rate of the nanocomposite’s core metals. This was observed by a decrease in cytotoxicity in PC-3 cells when compared to other gold or silver nanosystems for similar timeframes published in the literature. Full article

The reaction mechanism of the gold-catalyzed hydrothiolation of alkenes (1) with thiols (2) has been investigated in detail. The tetranuclear gold complex, (PPh₃)₄Au₄(SPh)₂(NTf)₂ (A), is a key intermediate in the catalytic hydrothiolation of alkenes. It forms instantaneously when PPh₃AuNTf₂ and PhSH are mixed in THF. Monitoring the reaction over time using ³¹P NMR spectroscopy revealed that gold complex A remained stable in the reaction system throughout the hydrothiolation process. In addition, we successfully observed a rapid ligand-exchange reaction between the thiolate group of gold complex A and thiols in solution. The gold-catalyzed alkene hydrothiolation reaction has been applied to the catalytic hydrothiolation of allenes, which have degenerate double bonds. Hydrothiolation of allenes proceeded regioselectively at the terminal double bond. However, the yield was lower than that observed for alkenes, and catalyst deactivation occurred. The hydrothiolation products of allenes were difficult to detach from the gold catalyst, necessitating an increase in the reaction temperature. Since high periodic transition metals such as gold and platinum are effective for hydrothiolation of alkenes and allenes, it is interesting to clarify whether iridium complexes, which belong to the same period as gold and platinum, could also catalyze alkene hydrothiolation. Through a detailed investigation of iridium ligands and reaction conditions, it was found that, in iridium systems, disulfide formation via oxidative coupling of thiols occurs preferentially over hydrothiolation reactions. This is likely due to steric hindrance around the iridium center, which inhibits alkene coordination to the iridium. Additionally, the hydrothiolation proceeding at low yields is believed to be a radical reaction involving electron transfer through the iridium complex. Full article

Background: Staphylococcus aureus bacteremia (SAB) is a common and life-threatening bloodstream infection often caused by methicillin-resistant SA (MRSA) isolates. Up to 35% of SAB patients fail to clear infection with gold-standard anti-MRSA antibiotics, even if the isolate meets susceptibility breakpoints in conventional assays in vitro. Such outcomes are termed persistent and may involve small colony variant (SCV) adaptation of SA in vivo. Methods: In this study, we assessed virulence phenotypes and mechanisms in persistent (PB) vs. resolving (RB) MRSA isolates from SAB. Results: Overall, PB isolates caused less hemolysis or biofilm formation than RB isolates, but proteolysis was equivalent. Attenuation of these virulence phenotypes increased longitudinally during the course of SAB. Although PB vs. RB isolates had similar human endothelial cell invasion rates, PB isolates more frequently formed SCVs intracellularly and inversely correlated with pH. Study PB and RB isolates exhibited distinct susceptibilities to prototypic human host defense peptides (HDPs), which were influenced by antibiotics and pH. Furthermore, mechanistic signatures of HDPs differed between PB and RB isolates. Conclusions: Together, these results reveal that MRSA isolates from PB vs. RB outcomes of SAB have differential virulence profiles that suggest coordinated immune subversion in PB. Understanding MRSA adaptations that promote persistence in SAB may enable innovative agents and strategies to address these challenging infections. Full article

Cardiac sarcoidosis (CS) is a critical and frequently underdiagnosed phenotype of sarcoidosis, characterized by non-caseating granulomatous infiltration of the myocardium. This review synthesizes current knowledge regarding the pathogenesis, diagnosis, and management of CS. The disease manifests with a heterogeneous clinical spectrum ranging from asymptomatic conduction abnormalities to life-threatening ventricular arrhythmias and heart failure. Diagnosis remains challenging due to the patchy distribution of granulomas, which limits the sensitivity of endomyocardial biopsy. Consequently, a multimodal diagnostic approach is essential, integrating advanced imaging modalities such as cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). These tools not only facilitate detection but also enable the differentiation of active inflammation from chronic fibrosis. Histopathological assessment, supported by specific immunophenotyping and electron microscopy, remains the gold standard for confirming diagnosis and excluding mimics like giant cell myocarditis or infectious granulomatous diseases. Management requires a multidisciplinary strategy combining immunosuppressive therapy, primarily corticosteroids and steroid-sparing agents, with guideline-directed cardiac care, including implantable cardioverter-defibrillators for arrhythmia risk stratification. Emerging biomarkers and artificial intelligence-driven imaging analysis promise to further refine risk stratification and therapeutic monitoring, advancing precision medicine in this complex disorder. Full article

Oxidative stress induced by excessive hydrogen peroxide (H₂O₂) is a critical pathological factor in skin aging, inflammatory disorders, and photodamage. While tocopherol (TCP) is a gold-standard antioxidant in cosmetics, its potential in H₂O₂-responsive systems remains underexplored. In this study, we report the design and characterization of ditocopheryl peroxalate (TOT), a novel tocopherol dimer linked via a H₂O₂-cleavable peroxalate linkage. TOT remains chemically stable under physiological conditions but undergoes selective chemiluminescence-like degradation upon exposure to H₂O₂, simultaneously scavenging H₂O₂ and liberating two TCP molecules. Notably, TOT demonstrated superior H₂O₂-scavenging efficiency and enhanced antioxidant and anti-inflammatory effects in H₂O₂-stimulated cells compared to monomeric TCP, while maintaining excellent biocompatibility. Structural analysis revealed that the rigid, linear configuration of TOT facilitates seamless integration into dipalmitoylphosphatidylcholine (DPPC) bilayers, yielding highly stable H₂O₂-responsive liposomes. These findings highlight TOT as a sophisticated multifunctional antioxidant platform for advanced cosmeceutical applications targeting photo-induced oxidative damage. Full article

The Jiaodong gold-mineralized area is one of the most significant gold districts in China. The newly discovered Moshan gold deposit is hosted in the Late Jurassic Queshan granite, previously considered a prospecting blind zone. In this study, pyrite from the Moshan gold deposit is examined as the primary research subject. To elucidate the ore-forming processes and genetic mechanisms of this deposit, we conducted a comprehensive mineralogical and geochemical study on pyrite, the principal gold-bearing mineral. EPMA and LA-MC-ICP-MS analyses reveal that the pyrite is slightly sulfur-deficient (average S/Fe ratio of 1.976) and exhibits trace element variations (As, Co, and Ni) strongly correlated with distinct metallogenic stages. Gold occurs in various forms, including visible inclusion gold, fracture gold, and invisible nano-particulate gold (Au⁰). The in situ sulfur isotope δ³⁴S values range from 7.11‰ to 9.40‰ (average 8.00‰), displaying high homogeneity and a positive deviation from the troilite in the Canyon Diablo iron meteorite. By integrating pyrite S-Fe relationships, Co-Ni-As systematics, and sulfur isotope characteristics, the study indicates that the Moshan gold deposit originates from a magmatic-hydrothermal source. The ore-forming materials predominantly derive from Mesozoic granite-derived magmatic-hydrothermal fluids, with a minor contribution from crustal basement materials. The depth of mineralization is interpreted as mid-shallow. These findings not only highlight the metallogenic potential of the Queshan granite and clarify the genetic relationship between the Moshan gold deposit and other regional gold deposits but also provide a novel theoretical foundation and technical support for deep gold exploration in the Jiaodong region. Full article

Surface plasmon resonance (SPR) sensors based on nanostructured metasurfaces offer enhanced sensitivity through engineered electromagnetic responses. In this study, we present an analytical and numerical investigation of the plasmonic behavior of gold nanopillar (Au-NP) and nanohole (Au-NH) arrays under both p- and s-polarized illumination, employing the Effective Medium Theory (EMT) in combination with the Transfer Matrix Method (TMM). The study combines Effective Medium Theory (EMT) and the Transfer Matrix Method (TMM) to describe the macroscopic optical response of multilayer plasmonic systems. For p-polarization, the nanostructure geometry strongly modulates the real and imaginary parts of the effective permittivity, with nanoholes supporting stronger SPR coupling and reduced optical losses compared to nanopillars. Under s-polarization, the effective permittivity remains largely invariant, primarily driven by the filling fraction. The analysis reveals that polarization-dependent behavior arises from boundary-condition-mediated coupling mechanisms governing surface plasmon excitation, aligning with classical plasmonic theory. Benchmarking against analytical dispersion relations and published experimental data for Au/BK7 systems shows close agreement within ±2°, confirming the physical consistency of the EMT–TMM framework. These results provide a systematic description of how polarization and filling fraction jointly modulate SPR coupling. The results offer a foundation for the rational design of plasmonic coatings and SPR-supporting metasurfaces by elucidating macroscopic coupling trends; however, no quantitative sensor performance metrics, such as refractive index sensitivity or figure of merit, are evaluated in this work. Full article

In search of a non-surgical alternative for male animal sterilization, this study investigated the use of gold-coated maghemite nanoparticles (γ-Fe₂O₃@Au) functionalized with citrate to produce testicular photohyperthermia (PHT). Wistar rats received an intratesticular injection of the fluid containing the nanoparticles (150 µL/testicle) followed by testicular irradiation with an LED light (808 nm). Testicular temperature was maintained at ~45 °C for 15 min. The results demonstrated a significant reduction in testicular volume and weight and sperm motility and normal morphology in PHT-treated animals, together with histopathological degeneration of seminiferous tubules. No treatment-related side effects or signs of systemic toxicity were observed. The biodistribution of the gold (Au) and iron (Fe) from the nanoparticles showed that the testes were the primary site of nanoparticle accumulation until day 56 post-treatment with possible renal excretion of Au. These findings support the prospect of testicular PHT mediated by γ-Fe₂O₃@Au nanoparticles as a neutering method for male animals. Full article

For nearly two decades, 12 months of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been the standard recommendation. Recent evidence suggests that abbreviated DAPT durations may reduce bleeding without compromising ischemic protection in selected patients. This review synthesizes randomized controlled trials, meta-analyses, and guideline updates published between 2023 and 2025, evaluating abbreviated DAPT strategies after ACS with percutaneous coronary intervention. Immediate aspirin withdrawal after PCI increased early stent thrombosis in NEO-MINDSET and STOPDAPT-3. One-month DAPT followed by ticagrelor monotherapy reduced bleeding without increasing ischemic events in ULTIMATE-DAPT and T-PASS. Three-month strategies demonstrated the most consistent safety profile, with TWILIGHT showing 50% bleeding reduction without increased death, myocardial infarction, or stroke (noting that TWILIGHT included 35% chronic coronary syndrome patients). Clopidogrel monotherapy after abbreviated DAPT increased myocardial infarction in STOPDAPT-2 ACS, highlighting the importance of potent P2Y12 inhibition. Meta-analyses confirmed bleeding reductions with early P2Y12 inhibitor monotherapy across broader populations, though benefits were more pronounced in East Asian cohorts. Abbreviated DAPT strategies offer personalized alternatives to standard 12-month therapy. Three-month DAPT followed by ticagrelor monotherapy represents a reasonable and evidence-supported strategy in selected patients with ACS. Risk stratification tools and individual patient factors should guide therapy duration decisions. Full article

Background: Fecal calprotectin (FC) is a well-established, non-invasive biomarker of intestinal inflammation and is widely used to differentiate inflammatory bowel disease (IBD) from functional gastrointestinal disorders. Although enzyme-linked immunosorbent assays (ELISA) remain the reference method, rapid immunochromatographic tests (ICTs) offer important operational advantages for point-of-care (POC) diagnostics. However, variability in analytical performance among available ICTs remains a concern. Objective: This study aimed to evaluate the diagnostic accuracy of the CerTest Calprotectin one-step card (CerTest Biotec S.L., Zaragoza, Spain) in comparison with the Actim^® Calprotectin lateral flow assay and the reference Calprest^® ELISA (Eurospital Diagnostics, Italy). Methods: A total of 128 fresh stool samples from patients clinically suspected of IBD were analyzed in parallel using all three assays. For the reference ELISA (Calprest^®), a cutoff value of >40 µg/g was applied according to the manufacturer’s instructions. For discrepant results between assays, a cutoff of 200 ng/mL (equivalent to 200 µg hCp/g stool) was employed for ELISA Calprest^® to resolve inconsistencies. The results of the lateral flow assays (CerTest^® Calprotectin ICT and Actim^® Calprotectin) were interpreted using their respective manufacturer-recommended thresholds. Diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using ELISA as the reference standard. Agreement between methods was assessed using Cohen’s κ coefficient. Results: Using ELISA, 47 of 128 samples (36.7%) exceeded the 40 µg/g cutoff. Compared with the Actim^® assay, the CerTest card demonstrated a sensitivity of 88.0% (95% CI: 75.7–95.5), a specificity of 100.0% (95% CI: 95.4–100), and a strong agreement (κ = 0.90). When compared with ELISA, the CerTest assay showed a sensitivity of 87.2% (95% CI: 74.3–95.2), a specificity of 96.3% (95% CI: 89.6–99.2), a PPV of 93.2%, an NPV of 93.2%, and a strong agreement (κ = 0.85). Conclusions: The CerTest Calprotectin one-step card provides a rapid and reliable detection of fecal calprotectin, demonstrating a high sensitivity and specificity that are comparable to both other lateral flow assays and the ELISA reference method. These findings support the use of rapid immunochromatographic testing as a valuable tool for preliminary screening and clinical decision-making in patients suspected of IBD, while acknowledging that histology remains the gold standard for definitive diagnosis. Full article

Background: African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars. While live attenuated vaccines (LAVs) provide protection, their use raises safety concerns. Therefore, the aim of the present study was to identify viral B-cell antigens associated with protection and to test their potential using highly immunogenic vaccine delivery platforms. Methods: We employed a microarray of 169 ASFV proteins expressed in a cell-free prokaryotic system to identify immunodominant antigens using sera from immune pigs. Six structural proteins were selected and formulated into AP205 virus-like particles (VLPs). Additionally, replication-defective vesicular stomatitis virus (VSV)-based vaccine candidates expressing glycosylated CD2v and EP153R proteins were generated. Three groups of specific pathogen-free pigs were immunized with either VLP- or VSV-based vaccines and challenged with the virulent ASFV Georgia 2007 strain. Control groups included pigs immunized with the attenuated ASFV Estonia 2014 strain and a naïve group. Results: Most vaccine candidates induced detectable antibody responses against target ASFV proteins. However, neither VLP- nor VSV-based vaccines provided protection, as clinical scores, hematology, cytokine responses, and viremia levels were similar to those in the negative control group. In contrast, only the ASFV Estonia 2014 strain elicited a robust T-cell response and protective immunity. Conclusions: These findings highlight the challenges in identifying protective B-cell antigens of ASFV and emphasize the pivotal role of cellular immunity in mediating protection. Full article

The Jiaodong gold concentration area, one of the most important gold metallogenic belts in China, has long been the focus of contentious debates regarding the genetic mechanisms and timing of gold mineralization. This study presents the new monazite U-Pb and pyrite Rb-Sr isotopic chronology data for the No. I ore zone of the Xidouya gold deposit, integrated with H-O-S isotopic geochemical analyses, to systematically investigate the mineralization age, ore-forming fluid sources and material provenance of the deposit. The main mineralization age of the deposit is constrained to 117 Ma, which is highly consistent with the regional mineralization peak of 120 ± 5 Ma in the Jiaodong gold concentration area. The δD values of the fluids range from −88.0‰ to −75.0‰ (mean = −82.6‰), while the δ¹⁸O_H2O values are calculated to be between 4.6‰ and 6.1‰. H-O isotopic data indicate that the ore-forming fluids of the Xidouya gold deposit originated from a mixed magmatic and meteoric source. As mineralization progressed from Stage I through Stage III, there was a detectable trend of increasing meteoric water involvement and a general decrease in δD and δ¹⁸O_H2O values. This signature indicates that the initial mineralizing system was dominated by primary magmatic water which subsequently underwent significant water–rock interaction with Early Cretaceous granitic bodies and progressive dilution by meteoric fluids in an open tectonic environment. Furthermore, sulfur isotopes (average δ³⁴S = +7.43‰) and the initial strontium isotope ratio (⁸⁷Sr/⁸⁶Sr = 0.71012) support a mixed-source model for the ore-forming materials, likely dominated by the anatexis of ancient crust with potential minor mantle-derived contributions. During the Early Cretaceous, lithospheric thinning and extension in the North China Craton (NCC) triggered large-scale magmatism and mineralization. The Xidouya gold deposit is a direct product of these regional tectono-magmatic-mineralizing events. This study provides new high-precision isotopic dating data for the Xidouya gold deposit, clarifies the evolutionary history of ore-forming fluids and the supply mechanism of ore-forming materials, and provides important theoretical insights and practical references for gold prospecting and exploration in the eastern part of the Jiaodong gold concentration area. Full article

The brittleness of 18-karat purple gold originates from the AuAl₂ intermetallic compound. This study investigates the microstructural modification of the AuAl₂ intermetallic compound by adding silicon (Si) and cobalt (Co) and by rapid solidification in copper molds. The samples with alloy additions from a traditional investment casting were compared with copper mold casting for grain boundary characteristics using SEM, EBSD, and TEM. SEM micrographs showed a reduction in grain size of copper mold casting from approximately within 150–200 μm to within 12–20 μm. EBSD showed a narrow grain size distribution in the Si–Co-modified alloy than in the Si-modified alloy, using the copper mold casting technique. TEM observations show that grain boundaries were closely packed, with ~80 nm-sized voids. XRD confirmed that all alloys retained the AuAl₂ intermetallic phase, with peak broadening in the modified and fast-cooling samples indicating crystallographic refinement. These results confirm that Si-Co additions with a fast cooling rate effectively refine the microstructure of the AuAl₂ intermetallic compound, making the alloy less brittle while preserving the purple gold color. Full article

Machine Learning (ML) models trained on large-scale datasets learn useful predictive patterns, but they may also memorize undesired information, leading to risks such as information leakage, bias, copyright violations, and privacy attacks. As these models are increasingly deployed in real-world and regulated settings, the consequences of such memorization become practical and high-stakes, reinforced by data-protection frameworks that grant individuals a Right to be Forgotten (e.g., the GDPR). Simply removing a record from the training dataset does not guarantee the elimination of its influence from the model, while retrain-from-scratch procedures are often prohibitive for modern architectures, including Transformers and Large Language Models (LLMs). In this work, we provide a perspective on Machine Unlearning (MU) in supervised learning settings, with a particular focus on Natural Language Processing (NLP) scenarios, grounded in a PRISMA-driven systematic review. We propose a multi-level taxonomy that organizes MU techniques along practical and conceptual dimensions, including exactness (exact versus approximate), unlearning granularity, guarantees, and application constraints. To complement this perspective, we run an illustrative benchmark evaluation using a standardized unlearning protocol on DistilBERT trained on a public corpus of news headlines for topic classification, contrasting the retraining gold standard with representative design-for-unlearning and approximate post hoc techniques. For completeness, we also report two oracle-assisted upper-bound baselines (distillation and scrubbing) that rely on a clean retrained reference model, and we account for their incremental cost separately. Our analysis jointly considers model utility, probabilistic quality, forgetting and privacy indicators, as well as computational efficiency. The results highlight systematic trade-offs between accuracy, computational cost, and removal effectiveness, providing practical guidance for selecting machine unlearning techniques in realistic deployment scenarios. Full article

Background: The biopsychosocial model positions fibromyalgia (FM) as the result of altered pain modulation shaped by trauma, psychological vulnerability, and structural stressors. The Sense of Coherence (SOC) may be a key resilience factor explaining differences in symptom severity after similar hardships. Objectives: To evaluate whether SOC mediates and/or moderates associations between trauma-related adversity and symptom burden in FM and whether comorbidities, medication use, healthcare factors, or treatment engagement modify these relationships. Methods: In this cross-sectional study, 2099 women with FM completed an online survey assessing adversity, psychosocial factors, core symptoms, healthcare support, treatment engagement, and medication use. A theory-driven SOC composite followed Antonovsky’s model (comprehensibility, manageability, meaningfulness) using the proxy SOC composite derived from a theory-driven framework that underwent internal construct validation, including discriminant validity analyses and latent structure evaluation, but it was not benchmarked against a gold-standard SOC questionnaire. Linear regression evaluated adversity–symptom associations, SOC mediation, and moderation by SOC and medication classes. Results: Higher adversity predicted lower SOC (e.g., cumulative abuse: B = −0.25), and lower SOC predicted higher symptom burden (e.g., Fibromyalgia Impact Questionnaire (FIQ): B = −6.77), producing significant indirect effects (cognitive symptoms: 0.22; FIQ: 1.69). SOC also moderated the effects of adversity on fatigue and global impact, weakening associations at higher SOC. Comorbidities showed modest influence: hypertension had minor indirect effects (ab = 0.27), scheduled consultation produced small interactions (cognition β = −0.38 to −0.46; fatigue β = ~0.05–0.06), and stroke showed the only clinically meaningful moderation (β ≈ 4.9–5.2), all far smaller than SOC effects. Conclusions: SOC functions as a central psychosocial pathway and resilience-related factor in the association between trauma and FM symptoms. Targeting SOC-related processes may help reduce symptom burden and improve outcomes. Full article