Search Results (10,988)

Microbial degradation of pectin is a fundamental process for the carbon cycle and a strategic approach for treating industrial residues. This study characterizes a novel marine bacterium, Paenarthrobacter sp. FR1, isolated from East China Sea intertidal sediment, which exhibits the ability to utilize pectin. Its draft genome (4.83 Mb, 62.92% GC content) is predicted to encode 4498 protein-coding genes. Genomic analysis revealed a rich repertoire of Carbohydrate-Active Enzymes (CAZymes) crucial for this process, including 108 glycoside hydrolases (GHs), 7 polysaccharide lyases (PLs), 35 carbohydrate esterases (CEs), and 11 auxiliary activities (AAs). Genomic analysis provides supportive evidence that FR1 may target both homogalacturonan (HG) and rhamnogalacturonan (RG) pectin domains, potentially through complementary hydrolytic and oxidative pathways. Phylogenomic analysis based on Average Nucleotide Identity (ANI, 83.56%) and digital DNA-DNA Hybridization (dDDH, 27.8%) confirmed its status as a potential novel species. Notably, FR1 is a rare Paenarthrobacter isolate with innate pectinolytic capability, a characteristic not previously documented in this genus. This strain’s unique enzymatic machinery highlights its importance in marine carbon cycling and provides a valuable biotechnological resource for degrading pectin-rich wastes. Full article

Climate change and global warming are deeply impacting natural foraging dependent upon rain fall. To understand how xerophytes cope with these dramatic changes, comparative transcriptomic profiling of Atriplex halimus and Atriplex leucoclada was investigated under drought stress. The data revealed both shared and species-specific adaptive mechanisms. Differentially expressed genes (DEGs) clustered into major conserved gene families, including stress signaling, transcriptional regulation, antioxidant defense, metabolism, transport, and hormone signaling. In A. halimus, drought tolerance was characterized by strong transcriptional regulation, redox balance, and energy homeostasis, highlighted by the up-regulation of WRKY, MYB, and SET-domain transcription factors, calcium transporters, SnRK1 kinases, and stress-protective proteins such as HSPs and LEAs. On the other hand, A. leucoclada exhibited broader signaling flexibility and structural reinforcement through enrichment of MAPKs, CDPKs, 14-3-3 proteins, and cell wall-modifying enzymes (XTHs, expansins, chitinase-like proteins), as well as high expression of transporters and hormone-responsive genes. Such patterns indicated distinct drought adaptation strategies: A. halimus relied on rapid transcriptional and redox adjustments suited for fluctuating moisture regimes, while A. leucoclada employed multi-layered, constitutive defenses for persistent arid conditions. Together, these results elucidate complementary molecular strategies enabling ecological divergence and drought resilience among closely related halophytes. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. During the NCAM polysialylation process, polysialyltransferases (polySTs), such as polysialyltransferase IV (ST8SIA4) or polysialyltransferase II (ST8SIA2), can catalyze the addition of CMP-sialic acid (CMP-Sia) to the NCAM to form polysialic acid (polySia). In this study, the docking models of polysialyltransferase IV (ST8Sia4) protein and different ligands were predicted using Alphafold 3 and DiffDock servers, and the prediction accuracy was further verified using the NMR experimental spectra of the interactions between polysialyltransferase domain (PSTD), a crucial peptide domain in ST8Sia4, and a different ligand. This combination strategy provides new insights into a quick and effective screening for inhibitors of tumor cell migration. Full article

This study characterizes two novel Bacillus phages, B450T and B450C, isolated from Bacillus thuringiensis VKM B-450 via mitomycin C induction, along with their endolysin, PlyC19. Both phages, siphoviruses with 41,205 bp genomes, lysed 38% of the tested Bacillus cereus sensu lato strains, with B450C showing enhanced lytic activity due to mutations in the repressor protein. PlyC19 lysed 56% of the strains tested, including Priestia flexa, demonstrating broader efficacy. Its Amidase_2 domain and dual SH3 cell wall-binding domains enable targeted peptidoglycan hydrolysis, with optimal activity at pH 9.0 and thermal stability up to 40 °C. We propose the taxonomic designation Bquatquinnuvirus eskimopiis for these phages, with B450T and B450C representing distinct strains, based on genomic divergence in the repressor protein’s HTH_Xre domain, consistent with their turbid and clear plaque morphologies, respectively. PlyC19′s broad specificity underscores its potential as an enzybiotic against multidrug-resistant Bacillus cereus group strains in food safety and medicine. Full article

The evolution of robust DNA repair mechanisms was a prerequisite for the conquest of land by plants, a transition that exposed them to harsh new environmental stressors. The poly (ADP-ribose) polymerase (PARP) family is central to this adaptation, as it orchestrates DNA repair and stress signaling pathways essential for coping with the elevated UV radiation and desiccation of terrestrial environments. Yet its early evolutionary origins are unknown. Here, we present a comprehensive reconstruction of the PARP family’s history across the plant kingdom. Our phylogenomic analysis reveals that PARP evolution ignited during the bryophyte radiation, expanding from a single ancestral algal gene into three distinct subfamilies (PARP1, PARP2, and PARP3). This diversification was driven by structural innovations in DNA-binding domains and a rewiring of transcriptional networks to respond to terrestrial challenges. We provide direct experimental support for this hypothesis through functional analysis of PARPs from the extremotolerant moss Syntrichia caninervis. We show that its PARP proteins provide multifaceted protection against UV radiation, heat, and genotoxic agents, and that recently duplicated PARP2 genes are already diverging in function. Our work pinpoints the molecular adaptations in a key DNA repair family that enabled the greening of Earth and uncovers novel genetic targets for enhancing crop resilience. Full article

Background/Objectives: The Fibroblast Growth Factor Receptor 1 (FGFR1, MIM*136350) is a protein member of the fibroblast growth factor receptor (FGFR) family, with various biological functions, such as the normal development control. It contains an extracellular site for the ligand (three Ig-like domains, IgI, IgII, IgIII), a single transmembrane and a cytoplasmic protein tyrosine kinase (TK) domain. Variants in this gene have been associated with a wide spectrum of genetic disorders, including the clinical entity known as FGFR1-related Hartsfield or Hartsfield syndrome (HRTFDS, MIM#615465), which is an autosomal dominant or recessive disorder characterized by the clinical association of split-hand/foot malformation (SHFM) and holoprosencephaly (HPE). Dysmorphic facies, including cleft/lip palate, genitourinary anomalies, cardiovascular defects and intellectual disability/developmental delay (ID/DD) can also be a part of the clinical picture. Methods: The malformation phenotype of HRTFDS has been reviewed in 26 previously reported patients in terms of single congenital defects, mutational spectrum, impacted protein domains and inheritance. Molecular basis, clinical management, main differential diagnoses and genetic counseling were also illustrated. Results: SHFM was identified in every patient. The other main associated features included craniofacial defects, skeletal malformation identified at radiography, genitourinary anomalies, HPE and cardiovascular disorders. FGFR1 causative variants mainly impact the TK domain and have a smaller impact on other protein sites (IgII, IgIII). Conclusions: This study extensively recapitulates the malformation phenotype associated with HRTFDS and the underlying molecular perturbations. A multidisciplinary clinical approach is fundamental, in which genetic counseling can have an important role. However, our results are partial and refer to a restricted number of patients, pointing out the necessity of other descriptions and similar research. Additional studies will expand clinical and molecular knowledge as well as further clarify the biological mechanisms. Full article

Chronic lymphocytic leukemia (CLL) is a heterogenous disease, with varied clinical outcomes. Multiplex assays used to measure soluble immune checkpoints offer a less laborious method of monitoring patients with CLL, but none of these panels have been validated. The aim of the study was to assess soluble immune checkpoint profiles in patients with CLL and to correlate these with independent prognostic markers such as β2-microglobulin (B2M), Rai stage, fluorescence in situ hybridization (FISH) status, and the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI). We measured plasma levels of soluble interleukin-2 receptor alpha (sCD25), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), galectin-9, programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) using cytometric bead array-based assays. We further measured plasma levels of B2M using an enzyme-linked immunosorbent assay (ELISA) kit. Soluble immune checkpoints were correlated with prognostic markers. The plasma levels of sCD25, TIM-3, galectin-9, PD-1, and PD-L1 were significantly increased in patients with CLL compared to the control group, p < 0.0001. Galectin-9 plasma levels were directly associated with B2M levels (β = 0.65, p = 0.012). Our findings suggest that galectin-9 may provide valuable prognostic significance for patients with CLL. Full article

Background/Objectives: To explore the protective effects of 7-Ketolithocholic acid (7-KLCA) against renal fibrosis and its mechanism, focusing on its interaction with farnesoid X receptor (FXR). Methods: In vitro, TGF-β-induced fibrosis in HK-2/NRK-49F cells and LPS-induced inflammation in HK-2 cells were detected by CCK-8, Western blot, and qPCR. In vivo, unilateral ureteral obstruction (UUO) and adenine (Ade)-induced mouse models were treated with a low/high-dose 7-KLCA or losartan. Renal injury was evaluated via H&E/Masson staining, serum creatinine (SCR), and blood urea nitrogen (BUN) levels. The 7-KLCA-FXR interaction was verified by molecular docking, CETSA, and DARTS. FXR downstream genes and related proteins were measured by WB and qPCR. Results: 7-KLCA inhibited the expression of fibrotic proteins (fibronectin, collagen-I) and reduced the LPS-induced release of inflammatory factors (IL-1β, IL-6). In mice, it alleviated renal swelling, collagen deposition, and tubular damage, while lowering serum SCR and BUN levels. Mechanistically, 7-KLCA stably bound to the FXR ligand-binding domain, enhanced its thermal stability and degradation resistance. It upregulated FXR and its downstream genes SHP and FGF15, thereby inhibiting the activation of TGF-β/Smad and Wnt/β-catenin pathways. Conclusions: This is the first study to clarify the molecular mechanism through which 7-KLCA targets FXR and dually suppresses the key pro-fibrotic pathways TGF-β/Smad and Wnt/β-catenin, thereby exerting anti-renal fibrosis effects. Full article

The Rift Valley fever virus (RVFV) is a highly pathogenic, mosquito-borne zoonotic virus that poses a significant risk to livestock, human health, and global public health security. Although RVFV is classified by the World Health Organization (WHO) as a priority pathogen with epidemic potential, no licensed vaccines or effective antiviral therapies are currently available. A limited understanding of the molecular mechanisms of RVFV entry has hindered therapeutic development. Here, we elucidate the molecular basis by which the RVFV envelope glycoprotein Gn recognizes its receptor, low-density lipoprotein receptor-related protein 1 (LRP1). Bio-layer interferometry (BLI) demonstrates that full-length LRP1 directly binds the head domain of Gn with nanomolar affinity in a Ca²⁺-dependent manner. Both LRP1 clusters II (CL II) and IV (CL IV) independently interact with Gn, with CL IV exhibiting stronger affinity, indicating a multivalent recognition mode. Structural modeling using AlphaFold 3 reveals pronounced charge complementarity between basic residues on Gn and acidic, Ca²⁺-coordinated pockets within LRP1. Mutations in key acidic residues in CL IV greatly reduced Gn binding, confirming the essential roles of Ca²⁺ coordination and electrostatic interactions. Collectively, our findings define a Ca²⁺-stabilized, electrostatically driven mechanism for RVFV Gn recognition by LRP1, providing molecular insight into viral entry and a structural framework for the rational design of vaccines and antiviral therapeutics. Full article

Bacterial blight in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to global rice production. The ability of Xoo to form biofilms is a key factor for its virulence. The OryR protein is a LuxR-type quorum-sensing regulator essential for biofilm formation and Xoo pathogenicity. However, the three-dimensional structure of OryR remains poorly understood. This study integrates homology modeling, molecular dynamics (MD) simulations, and virtual screening to elucidate the structure of OryR and identify potential inhibitors that target its ligand-binding domain. MD simulations confirmed the structural stability of OryR, and comparative analysis with experimentally determined structures of ligand- or inhibitor-bound homologs revealed a binding site in OryR with a distinct hourglass-like shape for long-range contacts. Virtual screening of over 200,000 compounds from four chemical libraries identified several promising inhibitor candidates, with the top compounds showing strong binding energies in both molecular mechanics-generalized Born surface area (−68.3 kcal/mol) and molecular mechanics Poisson–Boltzmann surface area (−19.3 kcal/mol) calculations. Overall, this study provides insights into the OryR structure and highlights potential inhibitors that can be developed as novel agents to control bacterial blight. However, additional experimental validations are required to refine and optimize these leads for drug development. Full article

The floral morphology of Rosa chinensis significantly influences its ornamental value. However, the molecular mechanisms underlying specific floral types remain poorly understood. Viridiflora, a stable genetic variant of R. chinensis, exhibits homeotic transformation of floral organs into sepal-like structures, providing a valuable model for studying floral organ identity and development. In this study, Viridiflora was compared with Old Blush to elucidate floral development through morphological observation, transcriptomic profiling, and functional genetics. Four distinct developmental stages were defined, encompassing the formation of sepal, petal, stamen, and pistil primordia. Transcriptome analysis identified candidate genes associated with the Viridiflora phenotype, among which RcAGAMOUS2 (RcAG2) and RcFRUITFULL (RcFUL) were selected for in-depth functional characterization. The proteins encoded by these two genes are hydrophilic, lack signal peptides and transmembrane domains, and contain multiple phosphorylation sites. They feature typical MADS-box family domains and show close phylogenetic affinity to Rosa rugosa. Subcellular localization showed their nuclear presence. Heterologous overexpression of RcAG2 and RcFUL in Arabidopsis resulted in notable phenotypic alterations: RcAG2 caused petal reduction and stamen exposure, while RcFUL led to greenish, leaf-like petals with pigmentation gradients, increased sepal number, and failed seed set. Conclusion: These results suggest that RcAG2 and RcFUL play key roles in floral organ development through genetic regulation, providing a theoretical foundation for further research on floral development in R. chinensis. Full article

Nanobodies (single-domain antibodies, VHHs) have emerged as versatile tools for evaluating and treating Alzheimer’s disease (AD). They offer distinct engineering benefits compared with traditional antibodies and small molecules, including small size, stability, and specificity. In AD, nanobodies have been shown in preclinical models to neutralize toxic amyloid-β oligomers, inhibit tau generation and aggregation, and modulate neuroinflammation, thereby demonstrating significant therapeutic potential. However, all nanobody applications in AD are discussed strictly as preclinical therapeutic potential rather than established clinical therapies, and direct clinical evidence in patients with AD is still lacking. Advanced engineering strategies, including intranasal and intrathecal routes, receptor-mediated transport, plasma protein binding with albumin, and focused ultrasound to facilitate brain penetration. Additionally, to improve nanobody delivery precision, half-life, and efficacy, strategies such as integrating nanobodies with nanoparticles, dendrimers, liposomes, and viral vectors are being employed. In fact, nanobodies are applied beyond monotherapy across multiple technological platforms to optimize brain delivery and target multiple targets. Nanobodies have been used on bispecific and trispecific antibody platforms, as well as in CRISPR/Cas9 editing and AI-driven technologies, to expand their applications. Recently, preclinical evidence has been mounting on the efficacy of nanobodies in clearing Aβ and tau, preserving synapses, and normalizing biomarkers. Comparison with FDA-approved anti-Aβ monoclonal antibodies (aducanumab, lecanemab, and donanemab) highlights opportunities and current translational gaps, including safety testing, half-life extension, and delivery optimization. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics. Full article

The genus Hyotissa (family Gryphaeidae) comprises ecologically and economically important marine bivalves, yet their molecular biology remains poorly characterized. This study presents de novo transcriptome sequencing of three Hyotissa species—H. sinensis, H. inaequivalvis, and Hyotissa sp.—to systematically identify and characterize the superoxide dismutase (SOD) gene family, a crucial component of the antioxidant defense system. We identified 46 SOD genes, including both Cu/Zn-SOD and Fe/Mn-SOD types, which exhibited considerable variation in molecular properties, domain architecture, and potential phosphorylation sites. Phylogenetic analysis revealed both evolutionary conservation and diversification of SODs across species. Notably, we identified homologs of two specialized SOD types: Dominin, which showed mutations in metal-binding sites suggestive of functional divergence, and copper-only SOD repeat proteins (CSRPs), which retained copper-binding residues but lost zinc-binding capacity. These findings suggest that the SOD family in Hyotissa has undergone significant functional diversification, potentially as an adaptive response to their high-oxygen, high-ultraviolet reef habitats. This study provides foundational transcriptomic resources for Hyotissa and offers new insights into the evolution and environmental adaptation of SOD genes in marine bivalves. Full article

Background: Pneumonia contributes to post-burn morbidity and mortality. Understanding the mechanisms that predispose burn patients to pneumonia is crucial to both stratifying patients at increased risk and developing targeted interventions. Methods: A prospective observational study was conducted with 47 human patients who sustained large burn injuries with serum collected on days 2 and 3 post-burn and assessed for Angiopoietin-1 (Ang-1) and -2 (Ang-2). C57BL/6 mice were subjected to either sham injury or a 12.5% total body surface area (TBSA) scald burn injury, and plasma and lungs were assessed. Results: Patients who developed pneumonia within 30 days of injury had higher serum Ang-2 and Ang-2/1 ratio on post-injury days 2 and 3. Similar to patient findings, we observed an increase in Ang-2 in burn mice compared to sham. Within the lungs of burn mice, we found significant increases in Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (TIE2) receptor transcript Tek, downstream mediators TNFAIP3 Interacting Protein 2 (Tnip2) and phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1), in addition to endothelial adhesion molecules intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), along with neutrophil infiltration and markers compared to sham. Conclusions: These findings suggest that burn injury increases Angiopoetin-2 and downstream signaling in the lungs, which may contribute to post-burn pulmonary dysfunction. Further studies are necessary to understand if modulating the Ang–TIE2 axis can protect against pneumonia post-burn. Full article