Four novel alkaloids, including three γ-lactam alkaloids (1-3) and one diketopiperazine (4), along with eight previously known compounds (5-12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the tentative stereochemical assignments of the side-chain double bonds in 2 and 3, were elucidated through comprehensive spectroscopic analysis and in comparison with the literature's data. All isolated compounds were evaluated for their anti-leukaemic activities against human leukaemia cell lines K562 and RS4;11 using the MTT assay. Compounds 4, 6, 7, and 9-12 exhibited notable cytotoxic activities against both RS4;11 and K562 cell lines, with IC₅₀ values ranging from 5.02 ± 2.33 to 31.85 ± 0.50 μM. The results of Western blotting and Annexin V-FITC/PI staining elucidated that compounds 4, 7, and 10 could induce apoptosis in both RS4;11 cells and K562 cells.

Nanoemulsions are promising nanotechnology-based delivery systems that may improve the stability, bioavailability, and cellular uptake of therapeutic agents. Silver nanoparticles (AgNPs) have been reported to exhibit high antibacterial and anticancer activities via several mechanisms, such as the generation of oxidative stress and disruption of cellular membrane integrity. Breast cancer (MCF-7) and ovarian cancer (SK-OV-3) represent two highly aggressive malignancies that pose major global health challenges. Brown algae oil is a natural marine-derived product with a number of bioactive compounds, including fatty acids, sterols, and antioxidants, responsible for its numerous biological activities. Oil extracted from the brown alga Turbinaria turbinata, using hexane as an organic solvent, was formulated with silver nitrate (AgNO₃) using a surfactant-stabilized spontaneous emulsification method to prepare a silver-loaded T. turbinata oil nanoemulsion (Ag-TTO-NE). The biological performance of the system was evaluated against human cancer cell lines, including MCF-7 (breast cancer) and SK-OV-3 (ovarian cancer), in addition to pathogenic bacterial strains, and for antioxidant activity. The results demonstrated that the silver-loaded oil nanoemulsion (Ag-TTO-NE) exhibited anticancer activities against MCF-7 (breast cancer) and SK-OV-3, with IC50 values of 105.86 and 72.45 µg/mL and a Selectivity Index of 2.34 and 3.41, respectively. The silver-loaded oil nanoemulsion (Ag-TTO-NE) possessed antioxidant and antimicrobial activities against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC90274) and Salmonella typhi (ATCC 6539). These results indicate that T. turbinata-based silver nanoemulsions deserve further exploration as multifunctional marine-derived nanoformulations. In silico ADMET analysis projected moderate to high oral absorption for most of the discovered compounds and suggested favorable pharmacokinetic properties of the individual ingredients. ADMET analysis suggested that the major compounds discovered by GC-MS have good medication-like characteristics. These computational predictions are supplemental information and are not to be taken as the pharmacokinetic behavior of the nanoemulsion itself. Overall, the present results are based on in vitro biological assays together with exploratory computational studies and constitute preliminary evidence for the subsequent exploration of this marine-derived nanoformulation.

Melanoma remains highly lethal with frequent resistance to current therapies. Here we identify a marine-derived cyclopentapeptide, turnagainolide B, as a potent anti-melanoma agent that selectively kills B16-F10 melanoma cells (IC₅₀ = 50 μM) with low toxicity to normal skin cells. Using bioassay-guided isolation, we also obtained a new analogue, turnagainolide H, and elucidated their structures and biosynthetic pathways. Mechanistically, turnagainolide B induces a previously undescribed "dual-hit" autophagic signature: it simultaneously promotes autophagy initiation (via PI3K/mTOR suppression, evidenced by ATG5 and LC3B-II upregulation) and blocks autophagic degradation (evidenced by p62 accumulation). Co-treatment with chloroquine partially rescued cell viability and decreased LC3B levels, confirming that cell death depends on active autophagic flux disruption. Transcriptomic analysis, together with AI target prediction and docking, identified PI3K as a potential direct target, with downregulation of PI3K, mTOR, and BNIP3 supporting an imbalanced autophagic state. In a syngeneic mouse melanoma model, turnagainolide B significantly suppressed tumor growth, reduced melanin content and Ki67 expression, and enhanced CD8⁺ T cell infiltration. Collectively, this work expands the chemical diversity of the turnagainolide family, uncovers a unique "dual-hit" autophagic mechanism, and establishes turnagainolide B as a promising lead for melanoma therapy.

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC-MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment.

Cardiac calcified amorphous tumours (CATs) are rare non-neoplastic intracardiac masses characterized by calcified nodules within an amorphous fibrinous matrix and may clinically mimic thrombi or cardiac neoplasms. We report two uncommon cases of right atrial CAT occurring in young women and provide a narrative review of the literature.

Two patients with right atrial CAT underwent multimodality imaging evaluation, including echocardiography, computed tomography, and cardiac magnetic resonance, followed by surgical excision and histopathological examination. A narrative review of published cases identified through PubMed and Embase between 1972 and 2025 was also performed.

The first patient presented with a calcified right atrial mass extending into the superior vena cava, associated with superior vena cava syndrome and autoimmune disease. The second patient, affected by end-stage renal disease on hemodialysis and thrombophilia, presented with a large calcified right atrial mass associated with a retained dialysis catheter fragment. Histopathological examination confirmed CAT in both cases. The literature review identified 112 published reports comprising 143 patients, including the two cases presented herein, highlighting frequent associations with end-stage renal disease, mitral annular calcification, and embolic complications.

Cardiac CAT remains a rare and likely underrecognized entity with heterogeneous clinical presentation and significant embolic potential. Multimodality imaging is essential for diagnosis and surgical planning, while early surgical excision should be considered in symptomatic or high-risk patients.

Background/Objectives: Sinonasal osteomas are benign, slow-growing tumors that are typically asymptomatic and incidentally detected. However, in rare cases, they may present with atypical and potentially serious complications involving other sinonasal, orbital, or intracranial structures. This review aims to synthesize these unusual manifestations and to highlight the underlying mechanisms, diagnostic challenges, and management implications. Methods: A narrative review of the literature was conducted, focusing on reported cases of sinonasal osteomas with rare or complicated presentations. Studies were analyzed with emphasis on clinical features, imaging findings, pathophysiological mechanisms, and treatment strategies. Results: Unusual presentations of sinonasal osteomas are primarily driven by sinus obstruction, progressive expansion, and skull-base erosion. These processes may result in complications such as pneumocephalus, intracranial mucoceles, cerebrospinal fluid leaks, orbital compression, and secondary infections. Clinical manifestations are often nonspecific, including headache, seizures, visual disturbances, or focal neurological deficits, which may delay diagnosis. High-resolution computed tomography is essential for identifying the osseous lesion and associated bone changes, while magnetic resonance imaging is critical for assessing soft-tissue involvement and intracranial extension. Management is individualized, with surgical resection indicated in most symptomatic or complicated cases, using endoscopic, open, or combined approaches. Conclusions: Although rare, atypical manifestations of sinonasal osteomas can result in significant morbidity. A mechanism-based understanding, supported by appropriate imaging, is essential for accurate diagnosis and timely management. Increased clinical awareness is crucial to improving outcomes in these uncommon but clinically significant cases.

Recovery after major head-and-neck reconstruction extends beyond flap survival and wound closure, involving swallowing, psychological adaptation, body image, and overall quality of life. Integrated multidimensional assessments remain limited in routine reconstructive outcomes research.

The aim of this study was to characterize and compare six-month multidimensional recovery-clinical, functional, nutritional, psychological, and body-image outcomes-between microvascular free-flap and regional pedicled-flap reconstruction and to identify factors that stratify risk for persistent functional and psychosocial impairment.

We conducted a single-center prospective cohort study at the "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania, enrolling 87 adults undergoing major reconstructive surgery after ablative treatment of head-and-neck defects (52 microvascular free flaps; 35 regional pedicled flaps). Patients were assessed at baseline and 6 months using the SF-36, WHOQOL-BREF, Body Image Scale (BIS), HADS, PHQ-9, GAD-7, Functional Oral Intake Scale (FOIS), speech intelligibility, and PEG/tracheostomy dependence.

At 6 months, most SF-36 and WHOQOL-BREF domains improved with moderate effect sizes (d = 0.3-0.7; all p ≤ 0.009), and body image distress decreased significantly (ΔBIS -2.9 ± 4.6; p < 0.001), whereas social functioning showed no robust gain (p = 0.098; not surviving false-discovery-rate correction). Pedicled reconstruction was associated with higher PEG dependence (37.1% vs. 9.6%; p = 0.005) and worse FOIS (4.7 ± 1.4 vs. 5.6 ± 1.2; p = 0.003). Major complications were linked to blunted or worsening psychological trajectories and a threefold higher rate of clinically significant depression (HADS-D ≥ 11: 66.7% vs. 18.7%; p = 0.001). In a reduced four-predictor multivariable model, pedicled flap (aOR 4.6), adjuvant radiotherapy (aOR 2.8), major complication (aOR 3.3), and lower baseline FOIS (aOR 0.5 per point) were independently associated with PEG dependence (optimism-corrected AUC 0.79). Clustering identified three recovery phenotypes-functional/emotional responders, psychological/body-image responders, and global slow recovery-with significantly different PEG rates (5.9%, 21.4%, 40.0%; p = 0.006). Exploratory mediation analysis suggested that the association between reconstruction technique and mental quality-of-life recovery was partly statistically accounted for by swallowing and body-image improvement.

Recovery after major head-and-neck reconstruction is multidimensional and heterogeneous. Baseline swallowing function, reconstruction technique, radiotherapy, and major complications jointly stratify risk for persistent functional and psychosocial impairment, supporting risk-adapted multidisciplinary rehabilitation and early psycho-oncologic screening.

Nano-carbon biointerfaces offer versatile platforms for cancer biomarker detection, but their progression from analytical proof-of-concept to clinically usable diagnostic evidence remains uneven. This scoping review maps 191 primary studies published from 2024 to 2026, covering nano-carbon families, surface chemistries, transduction architectures, biological matrices, and translational endpoints in cancer biosensing. The evidence space spans four nano-carbon dimensional classes: zero-dimensional carbon dots and quantum dots, one-dimensional carbon nanotubes, two-dimensional graphene-derived materials, and three-dimensional hybrid composites. Across these platforms, analytical sensitivity did not scale monotonically with nano-carbon dimensionality; instead, performance was shaped by the interaction between material architecture, biointerface chemistry, recognition strategy, transduction modality, and matrix context. A Translational Readiness Matrix showed that approximately 67% of studies remained at Low Evidence Level, whereas only approximately 10% reached Strong Evidence Level. Five recurring bottlenecks constrained translation: incomplete reproducibility reporting, limited Real-matrix Validation, scarce comparator-based clinical evidence, insufficient manufacturing-scale data, and weak regulatory or deployment planning. To address these gaps, this review proposes a nine-item minimum reporting checklist and a four-stage validation roadmap to support more reproducible, comparable, and clinically oriented nano-carbon biosensor development.

Lymph node metastasis (LNM) is a key prognostic factor in esophageal squamous cell carcinoma (ESCC), and accurate preoperative prediction remains challenging. Blood biomarkers provide a conventional, preoperative diagnostic technique that is cost-effective and free from radiation risks. So far, previous studies have been published on the precise diagnosis of lymph node metastases using conventional ultrasound or CT techniques. While there is a lack of research studies that address the diagnosis of LNM from blood biomarkers. In this work, we acquired a cohort of blood biomarkers of 1933 patients and designed a weighted neural network (WNN) model for the accurate prediction of LNM from blood biomarkers. The WNN model is designed with a neural network classifier trained on blood biomarkers labeled with pathological nodal (pN) stages of LNM. The experimental findings demonstrate that the WNN model achieved 83.1% accuracy and an AUC of 0.88 on the original, non-augmented test set for diagnosing LNM, while CT only achieved 50.4% accuracy (AUC 0.60) and ultrasound achieved 60.5% accuracy (AUC 0.67). Additionally, SHAP analysis reveals that three blood biomarkers-white blood cells (WBC#), monocytes (Mono#), and neutrophils (Neut#)-significantly impact the WNN model's output. This WNN model shows promise as a research tool to diagnose LNM.

Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations ≤ 5 μM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies.