Search Results (387)

A living organism can be regarded as a dissipative, self-organizing physical system operating far from thermodynamic equilibrium. Such systems can be effectively described within the framework of Markov jump processes subjected to an external driving force that sustains the system away from equilibrium—leading, in the special case of stabilization, to a non-equilibrium steady state (NESS). By combining the Markov formalism with concepts from stochastic thermodynamics, we demonstrate the temporal evolution of entropy in such systems: entropy decreases during growth and development, stabilizes at maturity under NESS conditions, and subsequently increases during aging, death, and decomposition. This characteristic trajectory, which we term the entropy bathtub, highlights the universal thermodynamic structure of living systems. We further show that the system exhibits continuous yet time-dependent positive entropy production, in accordance with fundamental thermodynamic principles. Perturbations of the driving force—whether reversible or irreversible—naturally capture the impact of external stressors, providing a conceptual analogy to pathological processes in biological organisms. Although the model does not introduce fundamentally new elements to the physics of life, it offers a simple tool for exploring entropy-driven mechanisms in living matter. Full article

The species Inula helenium belongs to the genus Inula (Asteraceae) and exhibits antibacterial and anti-inflammatory properties. It is used in respiratory and skin diseases. Its bioactivity is attributed to its eudesmanolide components, mainly to alantolactone and isoalantolactone. These components were isolated in high purity from the plant’s dried roots, either via multiple column chromatography separations or via repeated recrystallization. Two more eudesmanolides structurally similar to their parent compounds were isolated, namely 11,13-dihydro-alantolactone and 11,13-dihydro-isoalantolactone. The secondary metabolites and their derivatives were characterized in detail, for the first time, via NMR spectroscopy, GC-MS, and HRMS. Synthetic modification of the natural component structure was considered necessary for structure–activity relationship studies and biological tests. Thus, each compound was converted to its nitrile and then to the corresponding acid, or to its azide derivative and then corresponding amine. Antioxidant studies were conducted on the parent compounds, their derivatives, and the methanolic and hexane plant extracts using the DPPH radical method. The study revealed a strong antioxidant capacity of the methanolic extract. Acaricidal studies of both natural products and synthetic analogs against Varroa destructor and the comparison of their activity with the parent natural product costic acid, as well as one of its synthetic congeners, indicated that the “from nature to synthesis and vice versa” approach led to active compounds as well as to meaningful conclusions regarding the “pharmacophore” groups in the structural framework of the acaricides. Full article

Chondroitin sulfate is a glycosaminoglycan polysaccharide, playing key roles in a plethora of physiopathological processes typical of higher animals. The position of sulfate groups within CS disaccharide subunits composing the polysaccharide chain is able to encode specific functional information. In order to expand such a “sulfation code”, access to non-natural CS variants and mimics thereof can be pursued. In this context, an interesting topic concerns phosphorylated analogs of CS polysaccharides, as the replacement of sulfate groups with phosphates can lead to unreported activities of phosphorylated CS. In light of this, the phosphorylation reaction of a microbial-sourced, unsulfated chondroitin polysaccharide with phosphoric acid is reported in the present study, testing different microwave irradiation conditions and comparing them with conventional heating procedures. The obtained products were subjected to a detailed characterization, in terms of chemical structure and hydrodynamic properties, by 1D- and 2D-NMR spectroscopy and HP-SEC-TDA analysis, respectively. The characterization study showed how different reaction conditions can not only influence the regioselectivity and degree of phosphorylation but also trigger the formation of phosphate diester functionalities acting as cross-linkers between polysaccharide chains. The results from the screening presented in this work could be interesting for any research devoted to the regioselective phosphorylation of a polysaccharide. Full article

Polyphenols with antimicrobial and antibiofilm properties are gaining popularity due to their natural origins and relatively safe nature, and they have met the interest of the food industry because of their possible applicability as food preservatives. We have investigated the effect of different analogs of dimeric A-type proanthocyanidins (PACs) on four food matrix models, including unprocessed meat, fish, vegetables and dairy products previously contaminated with susceptible food pathogens. The best effects were achieved when cherry tomato was used as the food matrix for all the target bacteria (Staphylococcus aureus CECT 828, Listeria innocua CECT 910 and Bacillus cereus UJA27q) and for both temperatures tested (6 and 25 °C). Moreover, several combinations of these analogs also showed synergistic effects, mainly on S. aureus CECT 828, which may allow these antimicrobials to be used at lower levels in food matrices, which would promote their sensory acceptability. However, further studies should be conducted next to understand the mechanisms of these synergistic activities between the phenolic compounds against foodborne pathogens, as well as to ensure the absence of toxic effects when used as food preservatives. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Revodiol Calming Cream^® (RCC) is a novel dermocosmetic product containing cannabidiol (CBD) and Annona cherimola fruit extract, designed for the management of atopic-prone and sensitive skin. Objective: Clinically assess the efficacy and safety of RCC in the management of atopic-prone and/or sensitive skin. Materials and methods: A prospective study included 20 adults and 22 children with mild-to-moderate atopic-prone skin. RCC was applied daily, for 56 days. Clinical evaluation included the SCORAD index, pruritus and dryness scales; and a Visual Analog Scale (VAS). Biometric assessments (Mexameter^®, Tewameter^®, Visioscan^®, Corneofix^®) were performed. Subjective satisfaction and quality of life (DLQI) were also recorded. Results: RCC was well tolerated, with no significant adverse events. After 56 days, SCORAD scores decreased by 55% in adults and 60% in children. Pruritus and dryness were significantly reduced, and VAS scores indicated a 65% decrease in discomfort. Biometric assessments demonstrated improvements in erythema, skin barrier function, topography, and desquamation. Subjective satisfaction reached 75% in both populations, and DLQI improved by 23%. Conclusions: The synergistic combination of CBD, Annona cherimola extract, and natural humectants offers a safe and effective daily dermocosmetic care for both adults and children. Full article

The successful deployment of 3D printing in outdoor applications is contingent upon the selection of materials capable of withstanding the degrading effects of weather. This study evaluates the colorimetric performance of various 3D-printed polymers exposed to natural weathering conditions in Brasov, Romania, from November 2024 to March 2025. Color changes were monitored through spectrophotometry using a PCE-XXM 20 color meter, and data were recorded in the LAB color space. The results indicate substantial differences in color stability among the tested materials, with some exhibiting unacceptable levels of fading and discoloration. These findings have significant implications for the design and implementation of outdoor 3D-printed products in climates analogous to that of Brasov, underscoring the importance of selecting materials with demonstrated resistance to weathering and color change. Full article

Genome-based discovery provides a powerful approach for identifying bioactive natural products. In this study, Streptomyces sp. PSU-S4-23 was isolated from soil collected in southern Thailand. Genome analysis revealed a nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster highly similar to the reference actinomycin D cluster, including canonical NRPS genes and a cytochrome P450 associated with oxidative tailoring. Genomic comparison indicated that this strain is distinct from its closest relative S. caeni CGMCC 4.7426^T with ANIb and dDDH values below the species delineation thresholds. In agar diffusion assays, the crude extract exhibited antibacterial activity against Staphylococcus aureus (MSSA and MRSA), Bacillus subtilis, Bacillus cereus, Enterococcus faecalis, Staphylococcus epidermidis, as well as inhibition of Pseudomonas aeruginosa and Acinetobacter baumannii. LC–MS/MS profiling of the crude ethyl-acetate extract was performed. GNPS feature-based molecular networking revealed ions corresponding to actinomycin X₂ (m/z 1269.6), D (m/z 1255.6), and I (m/z 1271.6), confirming production of multiple actinomycin analogs. These findings highlight Streptomyces sp. PSU-S4-23 as a promising actinomycin-producing strain with potential relevance to antibiotic discovery. Full article

The proteasome β5 subunit plays a central role in protein degradation and is an established therapeutic target in glioblastoma. Marizomib (MZB), a natural β5 inhibitor, has shown promising anticancer activity, yet suboptimal pharmacological properties limit its clinical translation. Using a comprehensive computational approach, this study aimed to identify and characterize novel MZB analogs with improved binding affinity, stability, and drug-like profiles. An integrative in silico study was performed, including molecular docking, frontier molecular orbital (FMO) analysis, pharmacophore modeling, molecular dynamics (MD) simulations over 200 ns, MM/PBSA binding free energy calculations, and per-residue energy decomposition. ADMET profiling evaluated the pharmacokinetic and safety properties of MZB and top-performing analogs. Docking and pharmacophore modeling revealed strong complementarity between MZB analogs and the β5 catalytic pocket. MD simulations showed that MZBMOD-77 and MZBMOD-79 exhibited exceptional structural stability with low RMSD values (0.40–0.42 nm), persistent binding within the active site cavity, and significant disruption of hydrogen-bond networks in the active loop regions Ala19–Lys33 and Val87–Gly98. MM/PBSA analysis confirmed their superior binding free energies (−19.99 and −18.79 kcal/mol, respectively), surpassing native MZB (−6.26 kcal/mol). Per-residue decomposition highlighted strong contributions from Arg19, Ala20, Lys33, and Ala50. ADMET predictions indicated improved oral absorption, reduced toxicity, and favorable pharmacokinetics compared to native MZB. This integrative computational study identifies MZBMOD-77 and MZBMOD-79 as promising next-generation proteasome β5 inhibitors. These analogs mimic and enhance the inhibitory mechanism of native MZB, offering potential candidates for further optimization and preclinical development in glioblastoma therapy. Full article

Resource-based regions play an indispensable role as strategic bases for national energy and raw material supply in the global industrialization and urbanization process. However, intensive and large-scale natural resource exploitation—particularly mineral extraction—often triggers dramatic land use/cover changes, leading to a series of problems including cultivated land degradation, ecological function deterioration, and human settlement environment degradation. However, a systematic understanding of the functional transitions within the land use system and their drivers in such regions remains limited. This study takes Shenmu City, a typical resource-based city in the ecologically vulnerable Loess Plateau, as a case study to systematically analyze the transition characteristics and driving mechanisms of land use functions from 2000 to 2020. By constructing an integrated “element–structure–function” analytical framework and employing a suite of methods, including land use transfer matrix, Spearman correlation analysis, and random forest with SHAP interpretation, we reveal the complex spatiotemporal evolution patterns of production–living–ecological functions and their interactions. The results demonstrate that Shenmu City has undergone rapid land use transformation, with the total transition area increasing from 27,394.11 ha during 2000–2010 to 43,890.21 ha during 2010–2020. Grassland served as the primary transition source, accounting for 66.5% of the total transition area, while artificial surfaces became the main transition destination, receiving 38.6% of the transferred area. The human footprint index (SHAP importance: 4.011) and precipitation (2.025) emerged as the dominant factors driving land use functional transitions. Functional interactions exhibited dynamic changes, with synergistic relationships predominating but showing signs of weakening in later periods. The findings provide scientific evidence and a transferable analytical framework for territorial space optimization and ecological restoration management not only in Shenmu but also in analogous resource-based regions facing similar development–environment conflicts. Full article

Tyrosine kinases (TKs) and cyclin-dependent kinases (CDKs) contain reactive cysteines that can be exploited by targeted covalent inhibitors. In this exploratory computational study, we asked whether selected natural-product-like (NP-like) electrophiles bearing Michael-acceptor (MA) motifs could adopt geometries consistent with covalent approaches to these cysteines, in a manner analogous to approved covalent TKIs. Using AutoDockFR with cysteine-centered grids and explicit side-chain flexibility, we performed pocket-focused, within-receptor covalent docking for EGFR, VEGFR2/KDR, PDGFRβ (via PDGFRα surrogate), BTK, CDK7, and CDK12. Reference inhibitors (osimertinib–EGFR, ibrutinib–BTK, THZ1–CDK7, and THZ531–CDK12) reproduced the expected geometries and served as internal controls. NP-like electrophiles (parthenolide, withaferin A, celastrol, and curcumin as a low-reactivity geometry probe) displayed pocket-compatible orientations in several targets, particularly EGFR and BTK, suggesting feasible pre-reaction alignment toward the reactive cysteine. Although no quantitative affinity was inferred, the consistent geometric feasibility supports their potential as structural templates for covalent-binding natural scaffolds. These results provide a qualitative, structure-based rationale for further chemoproteomic and enzymatic validation of NP-derived or hybrid compounds as potential leads in cancer therapy, expanding covalent chemical space beyond existing synthetic scaffolds. Full article

Colletotrichum gloeosporioides causes rubber tree anthracnose and leads to serious loss in natural rubber production. Autophagy is a highly conserved process to maintain nutrient recycling and plays important roles in growth, development and pathogenicity in plant pathogenic fungi. The process of autophagy is modulated by a series of autophagy-related (ATG) genes. ATG16 is a subunit of the ATG12-ATG5-ATG16 complex which functions in a manner analogous to an E3-like enzyme which is essential for autophagosome formation. However, the function of the ATG16 homolog in C. gloeosporioides remains unknown. In this study, the ATG16 homolog of C. gloeosporioides was identified and named as CgATG16. The expression level of CgATG16 was particularly higher in conidium, germination, appressorium, and the early stage of infection, and significantly induced by nutritional deficiency. Absence of CgATG16 led to slower colony growth, decreased conidia production and germination rate, longer germ tube cells, lower appressorium formation rate and impaired pathogenicity to rubber tree leaves. Absence of CgATG16 resulted in lower melanin content with decreased expression of polyketide synthase gene CgPKS1 and scytalone dehydratase gene CgSCD1. Moreover, absence of CgATG16 also led to the universal autophagy marker ATG8-GFP failing to enter into the vacuoles in mycelium and during appressorium development with a significantly reduced autophagosome number. Both rapamycin and cyclic adenosine monophosphate (cAMP) partially restored the appressorium formation ability in CgATG16 knockout mutant. Absence of CgATG16 increased the activity of target of rapamycin (TOR) kinase and decreased the content of cAMP. These data suggest that CgATG16 contributes to the pathogenicity of C. gloeosporioides to the rubber tree by regulating the mycelium growth, melanin synthesis and the formation of invasion structure, and this process is related to autophagy mediated by TOR and cAMP signaling. Full article

Cembrane-type diterpenoids (cembranoids), natural compounds derived from soft coral Sclerophytum flexibile, exhibit diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral effects. Our previous research demonstrated that Sinulariolide, a member of this group, effectively inhibits TGF-β-induced IL-6 secretion, thereby suppressing inflammation-associated cancer development. Building on these findings, the present study employs a structure-activity relationship (SAR) approach to compare the anti-inflammatory properties of various cembranoids extracted from cultured soft coral Sclerophytum flexibile—a sustainable and environmentally friendly source that offers a consistent supply for research and therapeutic development. By isolating multiple cembrane-type analogs and analyzing their structural differences, we identified key chemical features that enhance their ability to interfere with TGF-β signaling and subsequent IL-6 production. The SAR analysis revealed distinct variations in anti-inflammatory efficacy among the tested compounds, pinpointing structural motifs crucial for inhibiting TGF-β-induced IL-6 secretion. These insights deepen our understanding of the molecular basis behind the anti-inflammatory action of cembranoids and guide the optimization of these compounds for potential therapeutic use. Full article

The search for sustainable and health-promoting food ingredients has positioned microalgae as promising candidates for the development of functional products. Haematococcus pluvialis, a unicellular green microalga, is the richest natural source of astaxanthin, a carotenoid with outstanding antioxidant, anti-inflammatory, and neuroprotective properties. In addition to astaxanthin, H. pluvialis provides high-value proteins, essential fatty acids, polysaccharides, and vitamins, which expand its potential applications in the food sector. This review compiles current knowledge on the biology and physiology of H. pluvialis, with emphasis on cultivation strategies, environmental stress factors, and biotechnological tools designed to enhance bioactive compound production. Advances in extraction and purification methods are also discussed, contrasting conventional solvent-based approaches with emerging green technologies. The integration of these strategies with biomass valorization highlights opportunities for improving economic feasibility and sustainability. Applications of H. pluvialis in the food industry include its use as a functional ingredient, natural colorant, antioxidant, and stabilizer in bakery products, beverages, meat analogs, and emulsified systems. Evidence from in vitro, in vivo, and clinical studies reinforces its safety and effectiveness. Looking ahead, industrial perspectives point to the adoption of omics-based tools, metabolic engineering, and circular economy approaches as drivers to overcome current barriers of cost, stability, and regulation, opening new avenues for large-scale applications in food systems. Full article

Isocyanide-based multicomponent reactions, such as the Ugi four-component reaction, are among the most relevant synthetic tools in modern organic chemistry. They have been successfully applied in natural product science for the synthesis of natural product analogs, for example, carbohydrates and steroids. However, the synthesis of analogs of other important groups, like triterpenoids, remains rarely studied. In the present work, we report the synthesis of four bis-amides via the Ugi reaction starting from masticadienonic acid, a triterpenoid isolated from Pistacia mexicana. Full article

Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents. Full article