Search Results (3,625)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a substantial public health threat worldwide. This trend is undoubtedly exacerbated by biofilm formation, which is closely related to bacterial virulence. Small RNAs (sRNAs) are post-transcriptional regulators of many biological processes in bacteria, including biofilm formation and virulence. The purpose of this study was to investigate the regulatory mechanisms of a novel sRNA (sRNA002) on biofilm formation and the virulence of CRKP. Through the CRISPR-Cas9 gene editing system, proteomic sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), crystal violet staining, scanning electron microscopy, hydrophobicity assay, a mouse intraperitoneal infection model, and the green fluorescent protein reporter system, we confirmed that the knockout of sRNA002 significantly downregulated the expression of the mrkA and mrkB genes, and weakened the virulence and biofilm formation ability of CRKP. Full article

Background: Scabies is a World Health Organization–designated neglected tropical disease of rising incidence with increasingly reported treatment failure, making objective verification of cure important. Dermoscopy is well established for diagnosis, but its role in assessing treatment response has never been mapped. Objectives: To map how dermoscopy assesses treatment response in scabies—which markers, timepoints and cure definitions are applied, and how it relates to clinical and microscopic standards. Methods: A scoping review following PRISMA-ScR searched PubMed/MEDLINE, Web of Science, EBSCO and Scopus (2016–2026, English) using a two-concept strategy (scabies × dermoscopy); eligibility required baseline dermoscopy plus at least one further, separately reported dermoscopic assessment during or after therapy. Two reviewers screened independently, supplemented by citation searching. Results: Ten studies were included. The same mite structure appeared under at least four names; assessment timepoints (day 2 to beyond day 28) and cure definitions were inconsistent. Dermoscopy was the genuine object of investigation in few studies; only one used ultraviolet-induced fluorescence to track response. Conclusions: Despite the disease’s recognised importance, dermoscopic monitoring of scabies remains a declared rather than a designed research aim. No standardised marker, timepoint or cure definition exists; consensus standards analogous to the 2020 IACS diagnostic criteria are needed. Full article

New deep-blue-emitting materials are crucial for Organic Light-Emitting Diode (OLED) technology, as iridium-based blue emitters often suffer from degradation and inadequate colour purity. Indium(III) complexes offer an alternative, since the d¹⁰ configuration of In³⁺ precludes metal-centred transitions, and emission arises from ligand-centred states via the chelation-enhanced fluorescence (CHEF) effect. We previously reported complexes 1 ([In(L^H)(H₂O)Cl₃]) and 2 ([In(L^Me)₂Cl₂][InCl₄]), which exhibited excitation-dependent emission, and the electronic transitions were assigned as ILCT for 1 and mixed ILCT/LL’CT for 2. Herein, we present a new complex, complex 3, i.e., [In(L^Morph)₂Cl₂][InCl₄], where L^Morph contains electron-donating morpholine substituents, in contrast to the acceptor chloride group in L^H and L^Me. Complex 3 was characterised by elemental CHN analysis, infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), ultraviolet–visible spectroscopy (UV-Vis), single-crystal X-ray diffraction analysis (SC-XRD), and photoluminescence. The ionic structure of 3 is analogous to 2, with a cis-octahedral [In(L^Morph)₂Cl₂]⁺ cation and tetrahedral [InCl₄]⁻ anion. The UV-Vis spectrum of 3 shows a significant bathochromic shift relative to 1 and 2 which is attributable to the morpholine group. TD-DFT calculations were employed to assign the electronic transitions. The introduction of a morpholino group into the pyridazine ring resulted in significant changes to the solid-state photoluminescence properties of the indium complex: (i) the emission maximum shifted to the red region (CIE 1931 coordinates: 0.1725, 0.2487), (ii) the lifetime increased by an order of magnitude, and (iii) the quantum yield rose to 15%. This work highlights that substituent variation on the pyrazolyl–pyridazine scaffold provides a versatile route to tune the structural and photophysical properties of indium(III) complexes. Full article

Despite the rapid expansion of targeted protein degradation (TPD), early characterization of PROTACs and molecular glues still relies predominantly on cellular degradation assays, making it difficult to determine whether poor degradation results from suboptimal E3 ligase engagement or from subsequent steps in the degradation mechanism. Moreover, productive degradation depends on balanced binary interactions, as both insufficient and excessively strong binding to either the E3 ligase or the protein of interest (POI) can impair degrader activity. Here, we report robust fluorescence polarization (FP) assays for the quantitative determination of ligand binding to the two most widely exploited E3 ligases, cereblon (CRBN) and von Hippel–Lindau (VHL). Using proprietary fluorescent tracers, the assays were validated with chemically diverse molecular glues, clinically relevant PROTACs, and canonical ligands, yielding affinity values in excellent agreement with published data. Both assays were successfully miniaturized to 384-well format while maintaining analytical performance and subsequently implemented in standardized ready-to-use formats, facilitating reproducible affinity measurements across laboratories. These assays establish a rapid and accessible binding-first platform that complements cellular degradation studies; supports rational degrader discovery, profiling, and optimization; and enables the identification of structurally novel E3 ligase recruiters. Full article

Background: Polydatin has shown anti-inflammatory, antioxidant, and cytoprotective effects in preclinical studies. Its development is limited by low oral bioavailability, extensive metabolism, and poorly defined tissue exposure. Objectives: This review summarizes the pharmacology and delivery systems of polydatin, distinguishes nano from non-nano formulations, and examines the evidence for improved exposure, tissue delivery, safety, and clinical translation. Methods: Relevant studies were identified through a structured PubMed search and assessed by formulation type, administration route, comparator, and reported endpoints. Results: Delivery strategies include liposomes, polymeric and polysaccharide nanoparticles, lipid-based formulations, inclusion complexes, solid-state systems, hydrogels, local matrices, and targeted systems. Only a few oral formulations have been compared directly with free polydatin using quantitative pharmacokinetic measurements. Many injectable and local studies report release, cellular uptake, fluorescence distribution, or pharmacodynamic effects, but these findings do not by themselves demonstrate improved bioavailability or drug-specific targeting. Evidence on repeat-dose toxicity, immunogenicity, carrier clearance, and manufacturing consistency remains limited. No clinical study of a polydatin nanocarrier was identified. Conclusions: Further development requires appropriate free-polydatin controls, measurement of polydatin and its metabolites, exposure–response analysis, fuller safety assessment, and reproducible product characterization. Full article

Nipah virus (NiV) is a zoonotic virus that causes severe encephalitis and respiratory disease with a mortality rate often exceeding 70%. Currently, there are no licensed vaccines or therapeutics for NiV disease. This study aimed to identify and experimentally evaluate small-molecule inhibitors targeting the NiV-G (attachment) glycoprotein using integrated in silico and in vitro approaches. A high-throughput virtual screening of >215,000 compounds was conducted against the NiV-G glycoprotein, using docking and molecular dynamics (MD) simulations. The next potential candidates were evaluated using an established, BSL-2-compatible recombinant Cedar virus (rCedV)-based green fluorescent protein (GFP) reporter virus expressing the NiV-F (fusion) and G glycoproteins (rCedV-NiV-B-GFP). During MD simulations, quercetin demonstrated the most stable binding, maintaining a consistent RMSD (3.25 ± 0.3 Å). In vitro testing showed dose-dependent inhibition of rCedV-NiV-B-GFP infection. Although quercetin alone was less potent (IC₅₀ = 24 µM; 95% CI: 7.6–93.6 µM) than a reference NiV-neutralizing monoclonal antibody mAb-7B7 (IC₅₀ = 0.027 μg/mL; approximately 0.00018 μM; 95% CI: 0.0108 to 0.0735), combination with ascorbic acid enhanced neutralization (IC₅₀ = 4.4 µM; 95% CI: 2.9–6.8 µM). Quercetin demonstrated a high Selectivity Index of >20.8. The study identifies quercetin as a promising small-molecule inhibitor of NiV cellular infection, potentially through a stable interaction with NiV-G at the ephrin-B2/B3 binding interface identified computationally. These findings highlight the importance of combining computational screening with BSL-2 cell-based bioassays to accelerate NiV countermeasure discovery. Full article

Compounds isolated from the macroalga Caulerpa sertularioides have been reported to exhibit cytotoxic activity. The objective of this study was to assess the antioxidant effects of compounds isolated from C. sertularioides as well as their antiproliferative effect against cancerous cell lines and to elucidate their chemical structure. The antiproliferative activity of C. sertularioides extracts was evaluated using the MTT standard assay in cancerous and non-cancerous cell lines. Morphological changes were observed via fluorescence microscopy, and the chemical structure of bioactive compounds was determined by nuclear magnetic resonance. Antioxidant activity was assessed using ABTS and DPPH methods. Among all extracts, the acetone extract exhibited the highest antioxidant activity (IC₅₀ of 27.3 ± 6.1 μg/mL) in the ABTS assay, which classifies it as a very potent antioxidant. Among the tested extracts, the hexane extract showed the strongest antiproliferative activity in breast (MDA-MB-231) and cervical cancer (HeLa) cell lines. The most active fraction (F15), obtained by open-column chromatography of hexane extract, exhibited the highest bioactivity against the MDA-MB-231 cell line (IC₅₀ of 55 ± 3.1 µg/mL); these cells exhibited morphological changes consistent with apoptosis. NMR analysis revealed signals tentatively assigned to 1-monolinolein, glycerol, bis(2-ethylhexyl) phthalate and bis(2-ethylhexyl) terephthalate. These findings support the potential of C. sertularioides as a source of bioactive compounds with antioxidant and antiproliferative properties. Full article

Oral nanocarrier development for inflammatory bowel disease (IBD) is complicated by inflammation-dependent changes in mucus, epithelial integrity, and immune-cell interactions. This critical narrative review examines comparative evidence from in vitro systems, animal models, and human intestinal tissue, alongside clinical studies, to assess how barrier state modifies formulation performance. Across the reviewed studies, particle size alone does not consistently predict lesion accumulation, while surface chemistry, coating, geometry, and stability in gastrointestinal fluids influence mucus interaction, cellular access, and payload release. Tissue-associated fluorescence, increased permeability, and cellular uptake do not independently establish intact-carrier transport or productive delivery. Clinical trials of selected oral nano-enabled formulations report improvements in some disease outcomes but do not establish inflammation-selective delivery as the underlying mechanism. We propose an evidence-informed benchmarking framework linking characterization in biological media to mucus transport or retention, epithelial–immune responses, spatial localization, target engagement, and safety. Matched healthy and inflamed comparators are central to testing selectivity, and preclinical findings must be distinguished from clinical validation. Artificial intelligence may support barrier-state-aware formulation optimization but requires standardized datasets and prospective experimental validation. Given the heterogeneous evidence base and limited direct human delivery studies, prospective validation should prioritize local payload delivery and therapeutic benefit without exacerbating intestinal barrier injury. Full article

One method for removing neonicotinoids from the environment that is considered safe, eco-friendly, and sustainable is phytoremediation. The aim of this study was to determine the effect of the sewage sludge-based compost rate on substrate activity in the presence of rapeseed (Brassica napus L.) and the effectiveness of the phytoremediation of substrate contaminated with imidacloprid (IM). A pot experiment was conducted using mineral substrate amended with sewage sludge-based compost (4 kg/m² and 8 kg/m²). IM aqueous solutions (250 ng/L and 500 ng/L) were applied to rapeseed seedlings, alongside compost substrate without IM (control). The following were determined: the content of IM in the substrate/rapeseed shoots, the main substrate properties, the activities of dehydrogenases and β-glucosidase, the number of bacteria, mold fungi and fluorescing Pseudomonas, and the number of ammonia-oxidizing archaea (AOA). It was reported that the application of compost significantly increased rapeseed shoot biomass and substrate enzymatic activity. However, the efficiency of IM uptake by plants decreased (by approximately 40%) with an increase in its dose in the substrate. At the same time, IM had a negative effect on the abundance of AOA (on average, 12% less than in the control), while the compost rate caused an increase in AOA abundance but with a lower IM dose. The obtained results indicate that direct phytoextraction from the shoots was limited, and the low apparent yield may be explained by unmeasured processes including transformation, sorption, retention by the roots or other losses. It should also be noted that an important limitation of these studies was the lack of determination of the IM content in roots and the identification of IM metabolites. Full article

Multimodal luminescent materials integrating spectral and temporal information are highly desirable for dynamic optical information encoding. However, constructing such systems often requires complicated molecular design or multiple synthetic steps. Herein, we report a simple Sb-introduction strategy to regulate excited-state dynamics in the zero-dimensional (0D) organic–inorganic hybrid metal halide (AP)₂ZnCl₄ (AP = 2-aminoacetophenone). The pristine host intrinsically combines prompt AP⁺ fluorescence with long-lived AP⁺-derived room-temperature phosphorescence (RTP). Upon Sb introduction, an additional broad Sb-related localized/self-trapped excitonic emission appears and the excited-state relaxation kinetics are redistributed while the native RTP pathway remains operative. These composition-dependent responses enable a proof-of-concept sequential time-gated optical encoding/decoding scheme with “WWW”, “SUV”, and “RTP” outputs. The results highlight dopant-mediated excited-state regulation in 0D hybrid metal halides for dynamic optical information encoding. Full article

Background and Objectives: Bile duct injury remains a major safety concern during laparoscopic cholecystectomy, and reliable interpretation of hepatocystic anatomy is fundamental to safe dissection. Artificial intelligence (AI)-based computer vision may support anatomical recognition, critical view of safety (CVS) assessment, and intraoperative decision support. This narrative review synthesized the current evidence, clinical applications, readiness for implementation, and future requirements of anatomy-aware AI during laparoscopic cholecystectomy. Materials and Methods: Five bibliographic databases were searched through 15 August 2026, supplemented by citation tracking and targeted searches. Studies were classified according to clinical task, dataset, reference standard, validation design, performance metrics, real-time capability, human factor assessment, and clinical readiness stage. The evidence base comprised 105 verified references: 50 primary AI reports and 55 contextual or methodological sources; 39 direct model development or evaluation reports were characterized in detail. Results: Investigated applications included landmark detection, semantic segmentation, CVS assessment, safe and hazard zone mapping, multimodal analysis incorporating indocyanine green fluorescence, automated documentation, education, and real-time perceptual prompting. Among the 39 direct reports, 24 remained at the offline proof of concept or internal validation stage, eight achieved temporal, external, or multicenter validation, six demonstrated prospective operating-room feasibility, and one reached post-deployment surveillance. The latter evaluated a surgical-process outcome rather than patient morbidity. Generalizability was constrained by dataset overlap, heterogeneous reference standards and metrics, domain shift, and underrepresentation of difficult cholecystectomy. No included study demonstrated reduced bile duct injury or other patient-level benefit. Conclusions: Despite progression to prospective feasibility and one post-deployment process surveillance report, no included study demonstrated a reduction in bile duct injury or another patient-level outcome. Current evidence supports adjunctive applications in documentation, video triage, education, coaching, and quality assurance, while surgeon-facing deployment requires further multicenter, human factor, and comparative-effectiveness evaluation. Full article

Inflammatory and nested testicular sex cord tumor (IN-TSCT) is a recently recognized, rare testicular sex cord–stromal neoplasm characterized by a recurrent EWSR1::ATF1 fusion and potentially aggressive clinical behavior. Because of its nested epithelioid morphology accompanied by prominent inflammatory infiltrates, IN-TSCT may be mistaken for seminoma, while frequent diffuse CD30 expression further complicates the differential diagnosis with lymphoma. We report a case of IN-TSCT in a 54-year-old man presenting with intermittent left testicular pain. Scrotal ultrasonography demonstrated a well-defined, heterogeneously hypoechoic intratesticular mass with minimally increased internal vascularity. Radical orchiectomy revealed a 1.5 × 1.4 cm epithelioid neoplasm arranged in nests and cords with a prominent inflammatory infiltrate. The tumor cells expressed the sex cord–stromal markers SF-1 and calretinin and showed diffuse CD30 expression. RNA-based next-generation sequencing identified an EWSR1::ATF1 fusion, establishing the diagnosis of IN-TSCT. Unexpectedly, the tumor also demonstrated strong ALK immunoreactivity with both the ALK1 and D5F3 antibody clones, despite the absence of an ALK fusion by RNA sequencing or an ALK rearrangement by fluorescence in situ hybridization. The combined expression of CD30 and ALK may mimic anaplastic large cell lymphoma and represents an important diagnostic pitfall. The patient remained free of recurrence or metastasis 18 months after orchiectomy. This case expands the recognized immunophenotypic spectrum of IN-TSCT and demonstrates that strong ALK immunoreactivity does not necessarily indicate an underlying ALK fusion or rearrangement. Given the potentially aggressive clinical behavior reported in IN-TSCT, long-term oncologic surveillance is warranted. Full article

Nanostructured carbon materials are low-dimensional systems relevant to oncology biosensing, with their utility arising from an electronic structure coupled to defect and edge states, a charge-transfer behavior and optical response that report molecular binding, an interfacial chemistry governing contact with the analyte, and, in selected cases, magnetic properties enabling manipulation and readout. In functional terms, these behaviors trace to specific quantum-relevant features—quantum confinement, edge and defect states, and the resulting size-dependent optical and charge-transfer responses—rather than to a generic quantum-material designation. This critical review treats nanocarbons as engineered biointerfaces whose performance is set by how the carbon surface behaves in biological fluid, how recognition chemistry is anchored, and how the binding event is transduced, with magnetic responsiveness, stability, reproducibility, and fabrication control as decisive constraints. The analysis separates three material classes—non-magnetic nanocarbon sensors, hybrid carbon–magnetic systems, and defect-associated or potentially metal-free magnetic carbons—while grading evidence as direct, adjacent, comparator-derived, or prospective. Directly, graphene, carbon nanotubes, carbon dots, graphene quantum dots, and magnetic carbon hybrids serve in electrochemical, optical and fluorescent, field-effect, and magnetic-assisted formats. Clinical translation, however, remains constrained by biofouling, protein-corona formation, matrix interference, unstable functionalization, batch variability, incomplete standardization, and scarce validation in real samples and patient cohorts. Metal-free or defect-associated magnetic carbons therefore warrant caution, remaining prospective platforms until the preservation of magnetic response, reproducible functionalization, matrix compatibility, safety, and measurable analytical advantage are directly demonstrated. Full article

Platelets express several glycophosphatidylinositol-(GPI-) anchored receptors, mainly involved in protection against lysis by activated complements. Most of these are well-characterised and are expressed on other blood cells. More recently, CD109 with a mass of 175 kDa was also shown to be a GPI-anchored receptor, surface expressed only on activated platelets, with a role as a co-receptor for transforming growth factor-β (TGF-β). CD109 is expressed on a wide range of cells and is a marker for various types of tumors. Activated platelets express an even larger GPI-anchored receptor at about 500 kDa. We have now isolated this and identified it as fibrocystin L, also known as polycystic kidney hepatic disease L1 (PKHD1L1). Fibrocystin L, like other platelet GPI-anchored receptors, is missing or deficient in paroxysmal nocturnal hemoglobinuria. Fibrocystin L is also expressed in activated T-cells and may be involved in immune responses. Recently, there have been additional reports of PKHD1L1 expression and roles as a coat protein of hair-cell stereocilia essential for normal hearing, as well as reports of them in the dentate gyrus in mice involved in susceptibility to seizure. In all these cases, GPI anchors were not reported, but neither were they tested for. During the fluorescence microscopy studies, we used CD109 as a control and observed that it is also a granule protein that had not been previously reported. Full article

Background/Objectives: The recent advances in pulmonary delivery have shifted the paradigm to the development of inhalable drug-loaded polysaccharide particles that can be positioned at the respiratory interface while reducing the systemic exposure. Quercetin has broad anticancer activity but remains difficult to translate because of its poor aqueous solubility, limited bioavailability and rapid metabolic loss. Here, we report quercetin-loaded chitosan/Salvia hispanica polysaccharide nanoparticles as a natural polyelectrolyte nanocarrier for pulmonary delivery in lung cancer. Methods: Central composite design (CCD) and artificial neural network (ANN) models were used for mapping the factors to responses. Results: The models displayed a higher predictive accuracy and optimization reliability for identifying the optimized formulation. The optimized nanoparticles showed a quasi-spherical morphology (mean hydrodynamic diameter = 331 ± 14.34 nm) with cationic ζ-potential of +36.3 ± 2.56 mV and polydispersity index of 0.15. The optimized formulation showed acceptable powder-flow characteristics, an encapsulation efficiency of 73.8 ± 0.73%, drug loading of 14.20 ± 0.22%, and biphasic release with sustained quercetin release over 48 h. In A549 and H460 cell lines, nanoencapsulation increased the antiproliferative effect of quercetin relative to the free compound, yielding lower IC₅₀ values after 48 h of exposure. The nanoparticles showed greater suppression of wound closure, increased reactive oxygen species fluorescence and clear cellular uptake. Blank nanoparticles produced only limited effects. Conclusions: These results indicate that CCD/ANN-guided chitosan/Salvia hispanica polysaccharide nanoparticles provide a promising nanodelivery tool for quercetin delivery and enhanced in vitro activity in lung cancer cells, while the observed aerosol performance advocates further investigation of their pulmonary delivery potential. Full article