Search Results (301)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by irreversible extracellular matrix deposition and high mortality, with aging representing its strongest risk factor. Increasing evidence suggests that cellular senescence is not merely a consequence of tissue injury but a central driver of disease progression. Senescent alveolar epithelial cells and fibroblasts contribute to impaired tissue repair and persistent fibrotic remodeling through the acquisition of a senescence-associated secretory phenotype (SASP), which promotes chronic inflammation and amplifies profibrotic signaling. This review provides a comprehensive synthesis of current evidence on the role of cellular senescence in IPF, focusing on key molecular mechanisms, including telomere attrition, mitochondrial dysfunction, oxidative stress, DNA damage response activation, and dysregulated transforming growth factor-β (TGF-β) signaling. A structured literature search was conducted using the PubMed, Scopus, and Web of Science databases to identify mechanistic, translational, and clinical studies related to cellular senescence in IPF. Relevant studies were selected based on conceptual relevance and scientific quality, and findings were qualitatively synthesized within a narrative-review framework. These interconnected pathways form self-reinforcing feedback loops that stabilize the senescent phenotype and sustain fibroblast activation. In addition, we critically evaluate emerging therapeutic strategies targeting senescence, including senolytic and senomorphic approaches, highlighting their potential to modify fundamental disease mechanisms rather than solely attenuating fibrotic progression. Preclinical and early clinical studies suggest that selective targeting of senescent cells may represent a promising avenue for intervention, although challenges related to specificity, safety, and biomarker development remain. Overall, this review positions cellular senescence as a central mechanistic link between aging and fibrosis and underscores its relevance as a translational target in IPF. Full article

Describing novel microbial species opens access to uncharted biosynthetic gene clusters and their associated secondary metabolites, offering fresh opportunities in the search for new antibiotics urgently needed to combat multidrug resistance. In this study, we describe a new species of Streptomyces, S. marxii sp. nov. (type strain VKM Ac-3100), an actinobacterium isolated from soil in the Yaroslavl Region of Russia. Using a polyphasic taxonomic approach that included whole-genome sequencing (WGS), we found that the strain’s average nucleotide identity (ANI) and digital DNA–DNA hybridisation (dDDH) values relative to its closest relative, S. maoxianensis, were 92.53% and 47.9%, respectively. Both values fell significantly below the species delimitation thresholds. Functional screening using the pDualrep2 dual fluorescent reporter system identified a unique SOS-silent antimicrobial profile characterised by growth inhibition without induction of the SOS response or translation stress. High-resolution mass spectrometry (HRMS) and genomic mining revealed that this activity is linked to the production of kinanthraquinone B ([M+H]⁺ m/z 275.0550), a rare polycyclic aromatic polyketide. Genomic analysis identified a specialised type II polyketide synthase (T2PKS) biosynthetic gene cluster (BGC) with evidence of acquisition via horizontal gene transfer (HGT). Our findings characterise S. marxii as a promising natural producer of rare catalytic inhibitors of DNA topoisomerases II and IV, offering a scaffold for the development of antibiotics with potentially lower genotoxicity. Full article

Intercellular mitochondrial trafficking has emerged as an important mechanism influencing tumor progression, metabolic adaptability, and cancer cell plasticity. Beyond their classical bioenergetic functions, mitochondria act as central regulators of redox homeostasis, signaling pathways, and epigenetic remodeling. Increasing evidence suggests that mitochondria can be transferred between tumor, stromal, and immune cells through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junctions, and cell fusion within the tumor microenvironment. This dynamic excshange enables metabolically compromised cancer cells to restore oxidative phosphorylation, optimize energy production, and survive under hypoxia and therapeutic stress. Mitochondrial transfer has been increasingly associated with enhanced cellular plasticity and adaptive phenotypic transitions, including the acquisition of stem-like features that contribute to tumor heterogeneity, metastasis, and treatment resistance. In addition to bioenergetic restoration, transferred mitochondrial DNA and metabolites participate in retrograde signaling, linking metabolic state to epigenetic regulation and transcriptional reprogramming. This metabolic epigenetic interplay supports tumor cell adaptation to environmental stress and therapeutic pressure. Although significant progress has been made, the precise mechanisms governing mitochondrial integration and their long-term impact on cellular phenotypes remain incompletely understood. A deeper understanding of these processes may reveal novel therapeutic strategies to disrupt tumor adaptability and progression. Specifically, targeting intercellular mitochondrial trafficking and its associated metabolic and epigenetic effects could help limit tumor plasticity, overcome treatment resistance, reduce disease recurrence, and improve overall clinical outcomes in cancer patients. Full article

Endophytic bacteria from plants adapted to arid and semi-arid environments represent an underexplored reservoir of microbial diversity with potential agricultural applications. Here, we report a polyphasic taxonomic and genome-based characterization of Achromobacter sp. isolates recovered from root and foliar tissues of Citrullus colocynthis and Peganum harmala, two medicinal plants thriving under harsh environmental conditions. Whole-genome sequencing, phylogenomic analyses, average nucleotide identity (ANI), digital DNA–DNA hybridization (dDDH), multilocus sequence typing, and detailed phenotypic profiling revealed three previously undescribed species, for which we propose the names Achromobacter colocynthi sp. nov., Achromobacter maghribensis sp. nov., and Achromobacter semiaridum sp. nov. Genome assemblies were highly complete (98.7–99.2%) with minimal contamination (<1%), supporting robust taxonomic inference. All three species displayed ANI and dDDH values below accepted thresholds relative to their closest phylogenetic neighbors, despite partial inconsistencies in 16S rRNA similarity for one isolate, highlighting the value of genome-wide metrics for species delineation. Phylogenomic analyses placed the novel taxa within Achromobacter sp. as distinct evolutionary lineages. Phenotypic characterization indicated broad metabolic versatility, including utilization of carbohydrates, organic acids, and amino acids, tolerance to moderate salinity and acidic pH, and resistance to multiple antimicrobial compounds, traits likely linked to adaptation to endophytic lifestyles under semi-arid conditions. Beyond their taxonomic novelty, the isolates exhibited in vitro traits associated with plant adaptation and stress tolerance, including IAA production, ACC deaminase activity, and tolerance to Zn, Cu, and Cd. Genomic analyses further indicated functions related to phosphate acquisition and stress response. These findings expand the taxonomic framework of Achromobacter sp., establish C. colocynthis and P. harmala as reservoirs of novel endophytic bacteria, and highlight their potential relevance for agricultural biotechnology in stress-prone environments. Full article

Reliable identification of deceased individuals may be difficult when conventional biometric methods such as facial recognition, fingerprint analysis, or DNA profiling cannot be applied. In such cases, medical imaging records acquired during a person’s lifetime may serve as an alternative source of identifying information. Certain anatomical structures visible in computed tomography (CT), including the sphenoid sinus, exhibit considerable inter-individual variability while remaining relatively stable within the same individual. This study investigates the feasibility of using sphenoid sinus morphology as an anatomical biometric for automated identification from head CT scans. Identification is formulated as a ranking problem in which a query CT examination is compared with a reference database using geometric descriptors derived from segmentation masks, reducing dependence on CT intensity values. The dataset consisted of CT scans from 816 individuals acquired in two patient positioning modes: Head First Supine (HFS) and Head First Prone (HFP). Several deep learning architectures, including YOLOv8 variants, YOLO11L-seg, UNet++, DeepLabV3+, HRNet, and SegFormer-B2, were evaluated for sphenoid sinus segmentation. Based on F1-score performance and cross-mode stability, YOLO11L-seg was selected and further trained to construct a database of binary masks representing individual sphenoid sinus anatomy. Identification was performed using pairwise mask comparison based on the Intersection over Union (IoU) metric. To reduce the influence of segmentation artifacts and slice-level variability, the final similarity score for each candidate was computed as the average of the four highest IoU values across slice comparisons. Individuals were ranked according to similarity, and identification was considered successful if the correct subject appeared among the top five candidates and exceeded a predefined similarity threshold. The proposed approach achieved Top-5 identification accuracies of 97.27% for HFP and 87.67% for HFS acquisitions. These results demonstrate the feasibility of using sphenoid sinus geometry as a stable anatomical biometric for automated identification. The key contribution of this study is the introduction of a ranking-based identification framework that utilizes anatomical biometrics derived from CT data for reliable patient matching. Full article

Gene amplification resulting from double strand breaks (DSBs) is a typical genetic alteration in tumorigenesis and drug-resistant progression. Amplified oncogenes and drug-resistant genes are present on extrachromosomal DNAs (ecDNAs), or chromosomal homogeneously staining regions (HSRs). Considering the role of mismatch repair (MMR) as a sensor of DSBs, we hypothesized that MMR may be involved in gene amplification. We used two MTX-resistant HT-29 colorectal cancer cell lines, which served as models with amplified genes mainly in HSRs or ecDNAs. Expression of MSH2, a key protein in MMR, was increased following the acquisition of MTX-resistant. MMR inhibition was achieved by depleting MSH2. Suppression of MMR led to decreased copy numbers of amplified genes as well as the quantity of ecDNAs and HSR. This was caused by the decreased efficiency of DSBs repair, which resulted from the reduced ability of MMR to recruit DSBs repair proteins. Additionally, it accelerated the formation of micronuclei (MN)/nuclear buds (NBUDs), which functioned to eliminate the amplified genes. Furthermore, the suppression of MMR was capable of inhibiting cell proliferation and enhancing MTX-sensitivity in ecDNA-containing cells. Conversely, suppression of MMR had no effect on gene amplification in HSR-containing cells. Our findings demonstrate that MMR plays a pivotal role in gene amplification through mediating DSBs repair pathways and facilitating the formation of MN/NBUDs in ecDNA-containing cells. MMR is likely to emerge as a prime therapeutic target worthy of in-depth exploration in future clinical investigations. Full article

Long non-coding RNAs (lncRNAs) and RNA–protein complexes (RNPs) are increasingly recognized as central to the regulatory complexity of modern eukaryotes. This review proposes that the remarkable diversity of eukaryotic systems arises from the long-term integration of ancient RNA/RNP mechanisms, layered with innovations introduced by successive symbioses. We outline four interconnected levels of symbiosis contributing to this process: (1) molecular symbiosis, involving dynamic assemblies of RNAs, proteins, and membraneless organelles (MLOs); (2) genome symbiosis, driven by the expansion of non-coding and repetitive DNA; (3) intracellular symbiosis, initiated by mitochondria acquisition; and (4) intercellular symbiosis, rooted in the cellular cooperation that enables multicellularity. We highlight lncRNAs and intrinsically disordered proteins (IDPs) as versatile mediators that interweave interactions across scales, predominantly within phase-separated condensates. Building upon these multi-level processes, we propose the framework of integrated symbiotic pleiotropy—a concept where molecular components acquire layered functional roles as a direct consequence of successive symbiotic acquisitions. This paradigm unites information layering, functional moonlighting, molecular tinkering, and exaptation into a coherent trajectory for eukaryotic evolution. Full article

Objectives: In the era of precision oncology, the management of lung cancer depends fundamentally on the acquisition of sufficient neoplastic material for both definitive histological subtyping and comprehensive molecular profiling. This study aimed to investigate molecular testing adequacy rates for small lung biopsy specimens obtained via minimally invasive procedures at three high-volume oncology centers. Recognizing that a significant subset of specimens remains insufficient for analysis, we evaluated the utility of cell pellets derived from residual fixative media as a supplemental resource for ancillary molecular testing. Methods: Over a six-month period, specimen handling workflows for small biopsies were assessed across three high-volume oncology centers. The pre-analytic molecular adequacy of formalin-fixed paraffin-embedded (FFPE) tissue sections from patients diagnosed with non-small cell lung cancer (NSCLC) was evaluated. During the final two months of the study, in cases where the primary FFPE tissue was deemed inadequate for molecular profiling, the residual fixative solution was recovered and processed to generate supplemental cell pellets. Results: Using adequacy thresholds of >200 tumor cells per section and a tumor cell fraction (TCF) of ≥10% or ≥5% (depending on specific assay requirements), the overall adequacy rates for FFPE samples were 80.6% (2986/3705) and 88.9% (3293/3705), respectively. During the final two months, 18.9% (154/816) of cases exhibited inadequate FFPE sections. However, of these cases, 56% (86/154) yielded adequate cell pellets based on cellularity evaluation and DNA quantification. These results indicate that cell pellets collected from the fixative medium of thoracic small biopsies are a valuable supplemental material for ancillary testing. Conclusions: This multi-center investigation demonstrates that a notable subset of NSCLC specimens obtained via minimally invasive biopsy remains insufficient for molecular analysis. Cell pellet samples obtained from residual fixative media serve as a critical supplemental resource, effectively increasing the success rate of molecular adequacy in clinical practice. Full article

Background/Objectives: FAM111A is a trypsin-like serine protease that has emerged as a regulator of DNA replication, and is directly related to genome stability, protein homeostasis, antiviral defense and cancer progression. Pathogenic variants in FAM111A are correlated with genetic syndromes such as Kenny–Caffey syndrome type 2 (KCS2) and gracile bone dysplasia/osteocraniostenosis (GCLEB/OCS). This study focuses on the evolutionary, genetic, and structural analysis of FAM111A, in order to identify key regions and candidate pharmacological targets that are related to this enzyme’s function. Methods: The methodology of this in silico study includes separate analyses at the sequence, structural and functional levels. Initially, data mining was carried out using NCBI/Protein (2025), and then data filtering was performed in order to identify representative FAM111A sequences for several species. Sequence analysis was then executed through multiple alignments and phylogenetic analyses. Through this, conserved domains and motifs were identified. For structural analysis, human pathogenic mutations and protein structures were identified through searches in biological databases including PDB and ClinVar, and then all data were analyzed in order to identify candidate pharmacological targets related to FAM111A function. Results: Approximately 1850 FAM111A protein sequences were retrieved for several species, and after filtering processes a dataset of 85 representative sequences was generated. Evolutionary analysis indicates that FAM111A originated in early metazoans, with progressive domain specialization leading to mammal-restricted acquisition of regulatory elements, including the PIP-box PCNA (proliferating cell nuclear antigen) interacting peptide and UBL (ubiquitin-like) domains. The ubiquitin-like/DNA binding domain and catalytic serine protease domain (SPD) are the most conserved, containing seven highly conserved motifs. The structural analysis was based on two protein structures and 34 critical mutations that accumulate in two distinct regions. Finally, by combining the results, six pharmacological targets and 100 inhibitors are proposed. Conclusions: Advancing the structural and function characterization of FAM111A, coupled with pharmacological target identification and evolutionary insights, will be critical to validate this underexplored protease as a therapeutic genetic target in genetic disorders, cancer, and antiviral responses. Full article

Orchid seed germination is heavily dependent on orchid mycorrhizal fungi (OMF) for nutrient acquisition in the field. Employing OMF to promote the germination and reproductive success of orchids is increasingly recognized as an effective conservation strategy. However, the success of this approach depends on identifying the most compatible fungal partners and integrating them properly into conservation programs. In this study, seeds of Anoectochilus roxburghii (Wall.) Lindl., a medicinal terrestrial orchid with Chinese national Level-II protected status, were co-cultured in vitro with 12 fungal strains from diverse sources to test seed preference to fungi and identify germination-promoting fungi. One strain (P2), isolated from host protocorms and identified as Ceratobasidium sp. based on rDNA-ITS phylogeny, showed the highest germination-promoting efficacy in in vitro symbiotic seed germination (SSG) experiments, yielding 41.09 ± 3.04% protocorm formation and 13.83 ± 3.15% seedling development at 60 days after sowing. Both values were significantly higher than those of other fungal treatments and the uninoculated control. Pilot trials of ex vitro and ex situ symbiotic seed germination demonstrated that strain P2 enhanced seedling development despite a low germination percentage caused by seed loss in artificial medium. These findings highlight the strong symbiotic preference of A. roxburghii seeds for strain P2 and demonstrate its potential as a valuable microbial resource for increasing seedling density in large-scale seedling propagation programs. Full article

Strain 11B20 was isolated from a commercial field of maize (Zea mays L.) located in the Yaqui Valley, Mexico. The draft genome sequence revealed a genomic size of 3,759,824 bp, 41.6% G + C content, 973,288 bp N50, 2 L50, and 29 contigs. According to the 16S rRNA gene, strain 11B20 belongs to the genus Bacillus. Genome annotation revealed 3952 coding DNA sequences (CDSs) grouped into 319 subsystems. Among these, several CDSs were associated with traits related to plant growth promotion, including (i) virulence, disease, and defense (33 CDSs); (ii) iron acquisition and metabolism (28 CDSs); and (iii) secondary metabolism (6 CDSs), among others. In vitro, metabolic analysis (IAA, siderophore biosynthesis; phosphorus solubilization; and tolerance to thermal, hydric, and saline stress) confirmed the genomic background of this strain. Finally, in planta assays showed that the inoculation of Bacillus sp. 11B20 significantly (p ≤ 0.05) increased the root length (48.2%) and root dry weight (35.4%) versus non-inoculated maize plants. Thus, this is the first report of Bacillus sp. 11B20 as a promising beneficial strain for sustainable corn production, and further research is needed to ensure the success of the application of this strain in agriculture. Full article

Human adenoviruses (HAdVs) remain prominent global human pathogens, particularly in dense, crowded populations. The advent of genomic and bioinformatic tools allows for high-resolution means to identify, characterize, and understand these pathogens. These tools also provide the basis for the standardization of names, as well as an accessible archive of all genotypes (“Human Adenovirus Working Group”). This overview and perspective of all the genotypes in one setting provides a better understanding of the mechanisms of their molecular evolution: genome recombination plays a major role in the emergence of novel adenoviral pathogens. In the context of the fidelity of their DNA polymerase replication machinery, this strategy provides entry into immune-naïve host populations through the acquisition of genome sequences that may include antigenic epitopes that have not circulated commonly, widely, or recently, as well as sequences encoding host cell entry proteins. Using the “chess” metaphor for describing the rapid evolution of RNA viruses, we propose a similar but diametrically opposed “White King Reigns in the Family of Human Adenoviruses”. Full article

Chronic ultraviolet (UV) exposure disrupts dermal collagen homeostasis and accelerates skin aging. This study evaluated the protective effects of black ginseng extract (BGE) against UV-induced photoaging in human dermal fibroblasts. BGE restored collagen-related markers, including COL5A1 and COL7A1, improved fibroblast proliferative capacity, and reduced senescence-associated changes under UV stress. Data-independent acquisition (DIA) proteomics identified broad pathway modulation by BGE, involving extracellular matrix remodeling, chromatin organization, and stress-response processes. To validate genome maintenance-related signals highlighted by proteomics, qPCR showed that BGE increased telomere/replication-associated genes compared with the UV group, including POT1 (2.29-fold) and ORC1 (6.70-fold). In addition, comet assay imaging indicated reduced UV-associated DNA damage features following BGE treatment. Overall, these findings indicate that BGE mitigates UV-induced photoaging phenotypes in fibroblasts, with collagen-related recovery and multi-level protective responses, supporting its potential as a natural bioactive ingredient for anti-photoaging skincare applications. Full article

Rare-earth-doped upconversion nanoparticles (UCNPs) exhibit upconversion luminescence upon excitation with infrared light and have been extensively utilized in the field of biosensing. In this study, a UCNPs-based biosensor with porous silicon (PSi) as the substrate was developed for the first time, enabling the detection of target DNA molecule concentration. First, a PSi substrate was prepared via electrochemical etching and subsequently functionalized to enable target DNA molecules to immobilize onto the inner walls of the PSi substrate’s pores. Then, UCNPs-labeled probe DNA molecules hybridized with the target DNA molecules, enabling indirect attachment of UCNPs to the inner walls of the PSi substrate. Subsequently, the sample surface is irradiated with a 980 nm laser. Upconversion fluorescence images of the sample, both before and after the biological reaction, are captured using an image acquisition device. Image processing software is employed to calculate the average change in grayscale values, enabling the determination of the molecular concentration of target DNA. The limit of detection (LOD) of this method for target DNA molecular concentration is 86 pM, demonstrating that it enables low-cost, highly sensitive, rapid, and convenient biological detection of target DNA molecules. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and limited patient compliance hinder widespread adoption. Recent advancements in artificial intelligence (AI) and bowel sound-based signal processing have enabled non-invasive approaches for gastrointestinal diagnostics. Among these, bowel sound analysis—historically considered subjective—has reemerged as a promising biomarker using digital auscultation and machine learning. Objective: This review explores the potential of AI-powered bowel sound analytics for early detection, screening, and characterization of colorectal cancer. It aims to assess current methodologies, summarize reported performance metrics, and highlight translational opportunities and challenges in clinical implementation. Methods: A narrative review was conducted across PubMed, Scopus, Embase, and Cochrane databases using the terms colorectal cancer, bowel sounds, phonoenterography, artificial intelligence, and non-invasive diagnosis. Eligible studies involving human bowel sound-based recordings, AI-based sound analysis, or machine learning applications in gastrointestinal pathology were reviewed for study design, signal acquisition methods, AI model architecture, and diagnostic accuracy. Results: Across studies using convolutional neural networks (CNNs), gradient boosting, and transformer-based models, reported diagnostic accuracies ranged from 88% to 96%. Area under the curve (AUC) values were ≥0.83, with F1 scores between 0.71 and 0.85 for bowel sound classification. In CRC-specific frameworks such as BowelRCNN, AI models successfully differentiate abnormal bowel sound intervals and spectral patterns associated with tumor-related motility disturbances and partial obstruction. Distinct bowel sound-based signatures—such as prolonged sound-to-sound intervals and high-pitched “tinkling” proximal to lesions—demonstrate the physiological basis for CRC detection through bowel sound-based biomarkers. Conclusions: AI-driven bowel sound analysis represents an emerging, exploratory research direction rather than a validated colorectal cancer screening modality. While early studies demonstrate physiological plausibility and technical feasibility, no large-scale, CRC-specific validation studies currently establish sensitivity, specificity, PPV, or NPV for cancer detection. Accordingly, bowel sound analytics should be viewed as hypothesis-generating and potentially complementary to established screening tools, rather than a near-term alternative to validated modalities such as FIT, multitarget stool DNA testing, or colonoscopy. Full article