Search Results (2,094)

Three new pyrrole alkaloids, streptopyrroles D–F (1–3), along with four known analogs (4–7) were isolated from Sea Anemone-Associated Streptomyces sp. S1502 via an OSMAC (One Strain Many Compounds)-based strategy. Their structures were elucidated through comprehensive spectroscopic analyses, including HRESIMS and 1D/2D NMR experiments (COSY, HSQC, and HMBC), and further confirmed by X-ray crystallography. Biological evaluation identified streptopyrrole (4) as an anti-MRSA (methicillin-resistant Staphylococcus aureus) agent, while 4 and 6 displayed broad-spectrum cytotoxicity and good selectivity against a panel of human cancer cell lines. Notably, 4 and 6 showed particularly potent activity against the lung cancer cell lines H1299, SW1573, and A549, with IC₅₀ values ranging from 5.43 to 16.24 μM. Further mechanistic investigation revealed that both compounds suppress the proliferation of lung cancer cells by inducing cell cycle arrest at the G0/G1 phase and impair metastatic potential by inhibiting migration and invasion. These findings not only expand the structural diversity of marine-derived pyrrole alkaloids but also reveal the anticancer mechanisms of 4 and 6, highlighting their promise as active candidates for further antitumor drug development, particularly in lung cancer. Full article

Autologous fat grafting is the main surgical technique for soft tissue reconstruction. However, its clinical use with more extended volumes is limited by repeated procedures due to the little possibility of banking tissue, donor-site morbidity and unpredictable graft resorption rates. To overcome these problems, adipose tissue engineering has focused on developing injectable scaffolds. Most of them are hydrogels that closely mimic the biological, structural and mechanical characteristics of native adipose tissue. This review provides an overview of current injectable scaffolds designed to restore soft tissue volume defects, emphasizing their translational potential and future directions. Natural injectable scaffolds exhibit excellent biocompatibility but degrade rapidly and lack mechanical strength. Synthetic injectable scaffolds provide tunable elasticity and degradation rates but require biofunctionalization to support cell adhesion and tissue integration. Adipose extracellular matrix-derived injectable scaffolds are fabricated by decellularization of adipose tissue. Accordingly, they combine bio-mimetic structure with intrinsic biological cues that stimulate host-driven adipogenesis and angiogenesis, thus representing a translatable “off-the-shelf” alternative to autologous fat grafting. However, despite this broad spectrum of available injectable scaffolds, the establishment of clinically reliable soft tissue substitutes capable of supporting large-volume and long-lasting soft tissue reconstruction still remains an open challenge. Full article

Human exposure to persistent organic pollutants such as polychlorinated biphenyls (PCB) and brominated flame retardants (BFR), including both legacy and emerging compounds, remains a concern due to their bioaccumulative nature and potential health effects. Comprehensive analytical methods are necessary to monitor these substances in complex biological matrices, such as human serum. A gas chromatography–mass spectrometry (GC-MS) method was developed for the simultaneous determination of 44 analytes, encompassing PCB and a broad spectrum of BFR with diverse physicochemical properties. The extraction procedure and GC-MS parameters were optimized using a design of experiments approach to maximize performance while minimizing analysis time. The method demonstrated high sensitivity, precision, and accuracy, thereby meeting internationally recognized validation criteria for biomonitoring applications. To further ensure analytical reliability, compound confirmation was achieved using gas chromatography–high-resolution mass spectrometry, providing enhanced selectivity and confidence in identification, particularly for low-level analytes. Key advantages of the method include its applicability to analytes with significantly different chemical behaviors and its capacity to quantify a large number of target compounds simultaneously. This makes it a powerful tool for assessing human exposure to both regulated and emerging halogenated contaminants. Full article

Brown seaweeds are marine bioresources rich in bioactive compounds such as carbohydrates, proteins, pigments, fatty acids, polyphenols, vitamins, and minerals. Among these substances, brown algae-derived polysaccharides (alginate, fucoidan, and laminarin) have promising industrial prospects owing to their distinctive structural features and diverse biological activities. Consequently, processing technologies have advanced substantially to address industrial requirements for biopolymer quality, cost-effectiveness, and sustainability. Over the years, significant progress has been made in developing various advanced methods for the sake of extracting, purifying, and structurally characterizing polysaccharides. Aside from that, numerous studies reported their broad spectrum of biological activities, such as antioxidant, anti-inflammatory, anticoagulant, and antimicrobial properties. Furthermore, these substances have various industrial, pharmaceutical, bioenergy, food, and other biotechnology applications. The present review systematically outlines the brown algae-derived polysaccharides treatment process, covering the entire value chain from seaweed harvesting to advanced extraction methods, while highlighting their biological activities and industrial potential as well. Full article

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

This study evaluated the thermal properties, crystallinity, particle size, morphology, and in vivo local inflammation and persistence of two poly-L-lactic acid (PLLA) injectable implants, Sculptra^® (PLLA-SCA) and GANA V^® (PLLA-GA). PLLA-SCA and PLLA-GA underwent differential scanning calorimetry and X-ray powder diffraction to evaluate their thermal properties and degree of crystallinity. X-ray powder diffraction spectra displayed a sharper, more intense peak for PLLA-GA than PLLA-SCA, with smaller peaks on either side of the main peak of PLLA-GA but not PLLA-SCA. Differential scanning calorimetry thermograms indicated three thermal events for both PLLA-SCA and PLLA-GA. For PLLA-SCA, the first two events occurred between 65 °C and 90 °C, and the third event occurred at 165 °C. For PLLA-GA all three events occurred between 156 °C and 169 °C. Heating samples to 120 °C and cooling to room temperature prior to differential scanning calorimetry resulted in no thermal events being observed between 65–90 °C with either product, while three events were observed with PLLA-GA and one event with PLLA-SCA between 156 °C and 169 °C. The median volume distribution diameter was 46.4 µm for PLLA-SCA and 31.7 µm for PLLA-GA. Scanning electron microscopy showed PLLA-GA particles were irregular in shape, had no sharp edges and had a wrinkled and crimped surface, while PLLA-SCA particles displayed plate-like shapes and had smoother surfaces. In vivo inflammatory reactivity scores indicated a slight reaction for PLLA-SCA at all time points (3.7 ± 1.1, 6.1 ± 1.6, 5.7 ± 1.2 and 6.2 ± 1.2 at 2, 12, 26 and 52 weeks, respectively), while for PLLA-GA, a moderate reaction was observed at 12 and 26 weeks (2.9 ± 1.5, 10.1 ± 1.0, 9.4 ± 0.7 and 7.1 ± 1.3 at 2, 12, 26 and 52 weeks, respectively). PLLA-SCA and PLLA-GA had similar persistence scores at 2, 12 and 26 weeks, while at 52 weeks the score was markedly higher for PLLA-SCA versus PLLA-GA (1.9 ± 0.2 versus 0.7 ± 0.2). In conclusion, PLLA-SCA is more amorphous than PLLA-GA. The single melting point of PLLA-SCA contrasts with the broader spectrum of melting points for PLLA-GA suggests a more homogenous formulation of PLLA-SCA. This, and its less crystalline structure, result in the slower degradation rate and more sustained biological response of PLLA-SCA compared with PLLA-GA. The physiochemical properties of PLLAs affect the biological response in clinical practice and should be taken into consideration when selecting a PLLA treatment for aesthetic use. Full article

Background/Objectives: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and increasingly are recognized as a continuum of interconnected conditions rather than isolated entities. Methods: A structured narrative literature search was performed in PubMed, Scopus, and Google Scholar for publications from 2015 to 2025 using combinations of different keywords: “cardiovascular disease spectrum”, “multi-omics”, “precision cardiology”, “machine learning”, and “artificial intelligence in cardiology”. Results: Evidence was synthesized across seven major clusters of cardiovascular conditions, and across these domains, common biological pathways were mapped onto heterogeneous clinical phenotypes, and we summarize how multi-omics integration, AI-enabled imaging and digital tools contribute to improved risk prediction and more informed clinical decision-making within this spectrum. Conclusions: Interpreting cardiovascular conditions as components of a shared disease spectrum clarifies cross-disease interactions and supports a shift from organ- and syndrome-based classifications toward mechanism- and data-driven precision cardiology. The convergence of multi-omics, and AI offers substantial opportunities for earlier detection, individualized prevention, and tailored therapy, but requires careful attention to data quality, equity, interpretability, and practical implementation in routine care. Full article

Background: In melanoma diagnostics key molecular markers, such as BRAF, NRAS, and KIT mutations also paved the way for targeted therapies. Immunotherapies, including immune checkpoint inhibitors like anti-CTLA-4 and anti-PD-1/PD-L1, have revolutionized treatment, improving survival outcomes for advanced-stage melanoma patients. Despite these advances, challenges such as resistance to targeted therapies and variability in patient responses to immunotherapy remain critical issues. The purpose of the project is to characterize the molecular landscape of a set of 28 malignant melanomas using next-generation sequencing, identify the prevalence and nature of class 3–5 variants (e.g., NRAS, BRAF, KIT, TP53), assess the genetic complexity and molecular patterns, and use these insights to inform personalized therapies and optimize patient stratification for potential combination strategies (targeted therapy followed by immunotherapy). Methods: We analyzed a set of malignant melanoma of the skin of 17 women (61%) and 11 men (39%) at the age of 23 to 85 years (median: 63 years) by tumor-only next generation sequencing. Results: 22/28 cases (79%) present a pathogenic or likely pathogenic variant with an allelic frequency of ≥5%. In total 42 distinct somatic pathogenic or likely pathogenic variants with an allelic frequency of ≥5% could be detected. The most frequent pathogenic molecular alteration in these melanomas were found in NRAS (25%) and BRAF (25%). The most frequent molecular alteration of unknown significance was found in FANDC2 (46%), NOTCH3 (39%), ARID1A (32%), PMS2 (32%), POLE (29%), NOTCH1 (29%), TSC2 (25%), SMARCA4 (25%), ATR (25%) and TERT (21%). Conclusions: While NRAS and BRAF were the most frequent actionable alterations (each 25%), a broad spectrum of variants of unknown significance (e.g., FANDC2, NOTCH3, ARID1A, PMS2, POLE, NOTCH1, TSC2, SMARCA4, ATR and TERT) also predominates, underscoring the genetic complexity of melanoma. These variants complicate clinical decision-making because their contribution to tumorigenesis, therapeutic response, and prognosis remains uncertain. Nevertheless, these variants also offer a valuable resource for future research, as they may uncover novel pathogenic mechanisms or therapeutic targets once their significance is elucidated. Integrating comprehensive genetic profiling with immunologic markers can enhance patient stratification and support rational, potentially synergistic strategies, such as combining targeted therapies with immunotherapy, to optimize clinical outcomes. This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma. Full article

Syringic acid (SA) is a natural derivative of syringaldehyde (SD), derived from lignin depolymerization. Its application in the food industry focuses on the properties of natural functional ingredients; it is mainly used as a food antioxidant and food preservative, but can also be used as an ingredient to enhance food flavor and functional foods. This compound exhibits a remarkable spectrum of biological activities, including potent antioxidant, anti-inflammatory, neuroprotective, hypoglycemic, detoxifying, and anti-cancer effects, positioning it as a highly promising candidate for pharmaceutical and nutraceutical applications. In this study, suitable sites were first screened through homologous sequence alignment, and a variant of aryl-alcohol oxidase (CgAAO) with high efficiency in catalyzing the conversion of SD to SA was obtained via site-directed mutagenesis. A deep eutectic solvent (DES) system based on choline chloride/urea (ChCl/UR) in water was developed to enhance SA production. Additionally, key parameters of the biological reaction were optimized, including temperature, pH, metal ions, as well as the type and dosage of DES. The optimal performance was achieved using recombinant E. coli pRSFDuet-CgAAO-Y335F whole-cell biocatalysts, yielding 75% and producing 0.75 g/L SA in 100 mM KPB buffer (pH 7.0) containing 5 wt% ChCl/UR and 1 mM Fe³⁺. This study established a novel biosynthetic pathway for SA that was efficient, mild, green, and environmentally friendly. Full article

Background: Coffin–Siris syndrome 12 (CSS12) is a recently described neurodevelopmental disorder caused by heterozygous pathogenic variants in BICRA, a gene encoding a core subunit of the non-canonical BAF (ncBAF) chromatin-remodeling complex. The condition is characterized by developmental delay, hypotonia, hypertrichosis, and joint laxity. However, long-term data remain limited, and systemic manifestations are incompletely defined. Case Description: We report a 22-year-old male with a de novo BICRA frameshift variant, c.2479_2480delinsA (p.Ala827Thrfs*15), previously included in the original cohort reported by Barish et al. Longitudinal follow-up revealed an expanded phenotype extending beyond neurodevelopmental features. Early findings included global developmental delay, growth hormone deficiency, short stature, and joint hypermobility. In adolescence and adulthood, he developed severe intestinal dysmotility requiring total colectomy, recurrent spontaneous pneumothoraces from bilateral apical bullous disease, and portal-vein thrombosis, representing visceral and vascular complications not previously emphasized in BICRA-related disorders. The identified BICRA variant truncates the coiled-coil domain critical for BRD9/BRD4 interaction, consistent with a loss-of-function mechanism. The patient’s systemic features suggest that BICRA haploinsufficiency affects not only neurodevelopmental pathways but also smooth-muscle and connective-tissue integrity. Conclusions: This case expands the phenotypic spectrum of BICRA-related CSS12, demonstrating that visceral and vascular involvement can occur alongside neurodevelopmental and connective-tissue features. Recognition of these broader manifestations underscores the need for lifelong multidisciplinary surveillance and contributes to understanding the diverse biological roles of the ncBAF complex in human development. Full article

Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions can achieve >96% absorption across 250–2500 nm and photothermal efficiencies exceeding 98% under one-sun illumination (1000 W·m⁻², AM 1.5G). Next, we highlight advances in solar steam generation and desalination: floating photothermal receivers on carbonized wood or hydrogels reach >95% efficiency in solar-to-vapor conversion and >2 kg·m⁻²·h⁻¹ evaporation rates; three-dimensional architectures recapture diffuse flux and ambient heat; and full-spectrum nanofluids (LaB₆, Au colloids) extend photothermal harvesting into portable, scalable designs. We then survey photothermal-enhanced thermal energy storage: metal-oxide–paraffin composites, core–shell phase-change material (PCM) nanocapsules, and MXene– polyethylene glycol—PEG—aerogels deliver >85% solar charging efficiencies, reduce supercooling, and improve thermal conductivity. In biomedicine, gold nanoshells, nanorods, and transition-metal dichalcogenide (TMDC) nanosheets enable deep-tissue photothermal therapy (PTT) with imaging guidance, achieving >94% tumor ablation in preclinical and pilot clinical studies. Multifunctional constructs combine PTT with chemotherapy, immunotherapy, or gene regulation, yielding synergistic tumor eradication and durable immune responses. Finally, we explore emerging opto-thermal nanobiosystems—light-triggered gene silencing in microalgae and poly(N-isopropylacrylamide) (PNIPAM)–gold nanoparticle (AuNP) membranes for microfluidic photothermal filtration and control—demonstrating how nanoscale heating enables remote, reversible biological and fluidic functions. We conclude by discussing challenges in scalable nanoparticle synthesis, stability, and integration, and outline future directions: multicomponent high-entropy alloys, modular photothermal–PCM devices, and opto-thermal control in synthetic biology. These interdisciplinary innovations promise sustainable solutions for global energy, water, and healthcare demands. Full article

Background/Objectives: Autism spectrum disorder (ASD) exhibits remarkable genetic heterogeneity involving hundreds of risk genes; however, the mechanism by which these genes organize within biological networks to contribute to disease pathogenesis remains incompletely understood. This study aims to elucidate these organizational principles and identify critical network bottlenecks using a novel integrative computational framework. Methods: We analyzed 893 SFARI genes using a three-pronged computational approach: (1) a Machine Learning Dynamic Perturbation Propagation algorithm; (2) a hypergraph construction method explicitly modeling multi-gene complexes by integrating protein–protein interactions, co-expression modules, and curated pathways; and (3) Hypergraph Neural Network embeddings for gene clustering. Validation was performed using hub-independent features to address potential circularity, followed by a druggability assessment to prioritize therapeutic targets. Results: The hypergraph construction captured 3847 multi-way relationships, representing a 45% increase in biological relationships compared to pairwise networks. The perturbation algorithm achieved a 51% higher correlation with TADA genetic evidence than random walk methods. Analysis revealed a hierarchical organization where 179 hub genes exhibited a 3.22-fold increase in degree centrality and a 4.71-fold increase in perturbation scores relative to non-hub genes. Hypergraph Neural Network clustering identified five distinct gene clusters, including a “super-hub” cluster of 10 genes enriched in synaptic signaling (4.2-fold) and chromatin remodeling (3.9-fold). Validation confirmed that 8 of these 10 genes co-cluster even without topological information. Finally, we identified high-priority therapeutic targets, including ARID1A, POLR2A, and CACNB1. Conclusions: These findings establish hierarchical network organization principles in ASD, demonstrating that hub genes maintain substantially elevated perturbation states. The identification of critical network bottlenecks and pharmacologically tractable targets provides a foundation for understanding autism pathogenesis and developing precision medicine approaches. Full article

A promising direction for the creation of new biologically active derivatives of the alkaloid lupinine is the synthesis of “hybrid molecules” that combine a fragment of the alkaloid and the pharmacophore of 1,2,3-triazole in their structure. From a biological perspective, this work presents the first X-ray diffraction study of a single crystal of (1S,9aR)-1-({4-[4-(Benzyloxy)-3-methoxyphenyl]-1H-1,2,3-triazol-1-yl}methyl)octahydro-2H-quinolizine, a new, recently synthesized 1,2,3-triazole derivative of lupinine. A comparison of theoretically predicted and experimentally observed structural parameters was carried out. The FTIR spectroscopy study and vibrational properties calculations allowed us to interpret the FTIR absorption spectrum and localize specific vibrational modes in quinolizidine, 1,2,3-triazole, and benzene rings. Such information can be fruitful for further characterization of the synthesis process and products. The molecular docking of the compound was performed. It was shown that the studied molecules are capable of interacting with the Mpro binding site via non-covalent and hydrophobic interactions with subsites S3 (Met165, Glu166, Leu167, Pro168) and S5 (Gln189, Thr190, Gln192), which ensure the stabilization of the Mpro substrate. Blocking of the active site of the enzyme in the region of the oxyanion hole does not occur, but stable stacking interactions with the π-system of one of the catalytic amino acids, His41, are observed. Full article

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models Full article

Rising quantities of a broad spectrum of contaminants due to high industrial and residential wastewater effluent loads have further raised the stakes with respect to environmental and health concerns. These demands, coupled with limitations in existing wastewater treatment solutions, have culminated in innovative supplementary solutions in the form of alternative wastewater treatments that, in general, encompass physical, chemical, or biological methods. By quantifying the resource consumption, pollution emissions, and ecological effects across the life-cycle in wastewater treatments, Life-Cycle Assessment (LCA) has proven valuable as a fundamental methodology for assessing and quantifying environment-related sustainability in wastewater treatments. Although valuable in its current applications, LCA is limited in its assessment of the relevant data related to the impacts of construction activities, novel contaminants emerging in wastewater treatment plants, and sludge disposal options. By considering pollutant type, wastewater treatment options, and important LCA methodological considerations, all encompassed within a structured framework including synthesis tables and comparative figures, our hope is that this study will prove valuable to rigorous decision-making processes based on related notions underpinning sustainability concerns in this domain. Full article