Search Results (840)

The rabies virus (RABV) phosphoprotein (P protein) has multiple functions, including acting as the essential non-catalytic cofactor of the viral polymerase (L protein) for genome replication and transcription; the principal viral antagonist of the interferon (IFN)-mediated innate immune response; and the chaperone for the viral nucleoprotein (N protein). Although P protein is known to undergo phosphorylation by cellular kinases, the location and functions of the phosphorylation sites remains poorly defined. Here, we report the identification by mass-spectrometry (MS) of residues of P protein that are modified by phosphorylation in mammalian cells, including several novel sites. Analysis of P protein with phospho-mimetic and phospho-inhibitory mutations of three novel residues/clusters that were commonly identified by MS (Ser48, Ser183/187, Ser217/219/220) indicate that phosphorylation at each of these sites does not have a major influence on nuclear trafficking or antagonistic functions toward IFN signalling pathways. However, phosphorylation of Ser48 in the N-terminus of P protein impaired function in transcription/replication and in the formation of replication structures that contain complexes of P and N proteins, suggestive of altered interactions of these proteins. The crystal structure of P protein containing the S48E phospho-mimetic mutation indicates that Ser48 phosphorylation facilitates the binding of residues 41–52 of P protein into the RNA-binding groove of non-RNA-bound N protein (N⁰), primarily through the formation of a salt bridge with Arg434 of N protein. These data indicate that Ser48 modification regulates the cycling of P-N⁰ chaperone complexes that deliver N protein to RNA to enable transcription/replication, such that enhanced interaction due to S48E phospho-mimetic mutation reduces N protein delivery to the RNA, inhibiting subsequent transcription/replication processes. These data are, to our knowledge, the first to implicate phosphorylation of RABV P protein in conserved replication functions of the P gene. Full article

The development of functional endothelial monolayers on synthetic vascular grafts remains challenging, particularly for small-diameter vessels (<6 mm) prone to thrombosis. Here, we present a pharmacological strategy combining 8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt (pCPT-cAMP, a tight junction promoter) with nitric oxide/cGMP pathway agonists 3-morpholinosydnonimine (SIN-1), captopril, and sildenafil) to enhance endothelialization. In human umbilical vein endothelial cells (HUVECs), this four-agent cocktail induced a flat, extended phenotype with a 3-fold increased cell area and 57.5% fewer cells required for surface coverage compared to controls. Immunofluorescence analysis revealed enhanced ZO-1 expression and continuous tight junction formation, while sustained nitric oxide (NO) production (3.9-fold increase) and restored prostacyclin (PGI₂) secretion demonstrated preserved endothelial functionality. Anticoagulation assays confirmed a significant reduction in thrombus formation (p < 0.01) via dual inhibition of platelet activation and thrombin binding. These findings establish a synergistic drug combination that promotes rapid endothelialization while maintaining antithrombogenic activity, offering a promising solution for small-diameter vascular grafts. Further studies should validate long-term stability and translational potential in preclinical models. Full article

Superhydrophobic coatings possess distinct wettability characteristics and hold significant potential in metal corrosion protection and underwater drag reduction. However, their practical application is often hindered by poor durability arising from the fragility of their micro/nanostructured surface roughness. In this study, a durable superhydrophobic coating featuring a hierarchical, hydrangea-like micro/nanostructure was successfully fabricated on an aluminum alloy substrate via a simple one-step cold-spraying technique. The coating consisted of hydrangea-shaped SiO₂ nanoparticles modified with 1H,1H,2H,2H-perfluorodecyltrimethoxysilane (PFDT) to produce multiscale roughness, while epoxy resin (EP) served as the binding matrix to enhance mechanical integrity. The hydrangea-like SiO₂ nanostructures were characterized by solid cores and wrinkled, petal-like outgrowths. This unique morphology not only increased the surface roughness but also provided more active sites for air entrapment, thereby enhancing the coating’s overall performance. The h-SiO₂@PFDT-EP composite coating exhibited excellent superhydrophobicity, with a WCA of 170.1° ± 0.8° and a SA of 2.7° ± 0.5°. Durability was evaluated through sandpaper abrasion, tape peeling, acid and alkali immersion, artificial weathering, and salt spray tests. The results demonstrated that the coating retained stable superhydrophobic performance under various environmental stresses. Compared with bare 6061 aluminum and EP coatings, its corrosion current density was reduced by four and three orders of magnitude, respectively. Furthermore, the coating achieved a maximum drag-reduction rate of 31.01% within a velocity range of 1.31–7.86 m/s. The coating also displayed excellent self-cleaning properties. Owing to its outstanding durability, corrosion resistance, and drag-reducing capability, this one-step fabricated superhydrophobic coating showed great promise for applications in marine engineering and defense. Full article

The call for new approaches to prevent and treat metabolic syndrome-related diseases has led to research on the use of lacto-fermentative probiotics with beneficial metabolic properties like Lactobacilli. Here, we characterize the probiotic properties of a novel strain, Lactiplantibacillus plantarum CNTA 628, and investigate its potential anti-obesity and health-promoting activities in the Caenorhabditis elegans model, additionally elucidating the molecular mechanisms involved. Lactiplantibacillus plantarum CNTA 628 exhibited sensitivity to the entire spectrum of antibiotics analyzed, gastric and intestinal resistance in vitro, β-galactosidase and bile-salt hydrolysate activities, and the capacity to form biofilms and produce SCFAs. In addition, it reduced the binding of the pathogenic E. coli O157:H7 to intestinal epithelial cells (Caco-2) and exerted immune-modulating effects in cellular models. Supplementation with this probiotic significantly reduced C. elegans fat accumulation by more than 18% under control and high-glucose conditions, lowered senescence, improved oxidative stress, and significantly enhanced lifespan without affecting the development of the worms. Gene expression analyses evidenced that L. plantarum CNTA 628 plays a role in regulating daf-22 and maoc-1 gene expression, both linked to beta-oxidation pathways. Our results demonstrate the health-benefiting properties of this novel strain and suggest its potential as probiotic candidate for the prevention and treatment of metabolic syndrome-related conditions. Full article

A fluorescent sandwich assay was devised to quantify CK-MB. In a typical immunoassay, antibodies bind to the target, and the detected signal is quantified according to the target’s concentration. We innovated a unique fluorescence assay known as the “enzyme-linked aptamer assay” (ELAA) by substituting antibodies with a pair of high-affinity aptamers labelled with biotin, namely apt. A1 and apt. A2. Avidin-labelled ALP binds to biotin-labelled aptamers, hydrolyzing its substrate, 2-phosphoascorbic acid trisodium salt, resulting in the formation of ascorbic acid. The catalytic hydrolysate functions as a reducing agent, causing the deterioration of MoS₂ nanosheets. This results in the transformation of MoS₂ nanosheets into nanoribbons, leading to the release of quenched AGQDs. The reestablishment of fluorescence is triggered by Förster Resonance Energy Transfer (FRET) between the MoS₂ nanoribbons and AGQDs, enhancing the sensitivity of disease biomarker detection. The working range for detection falls between 2.5 nM and 160 nM, and the limit of detection (LOD) for CK-MB is verified at 0.20 nM. Full article

A group of sulfonium and selenonium salts bearing diverse benzylidene acetal substituents on their side chain moiety were designed and synthesized. Compared with our previous study, structural modifications in this study focused on multi-substitution of the phenyl ring and bioisosteric replacements at the sulfonium cation center. In vitro biological evaluation showed that selenonium replacement could significantly improve their α-glucosidase inhibitory activity. The most potent inhibitor 20c (10.0 mg/kg) reduced postprandial blood glucose by 48.6% (15 min), 52.8% (30 min), and 48.1% (60 min) in sucrose-loaded mice, outperforming acarbose (20.0 mg/kg). Docking studies of 20c with ntMGAM presented a new binding mode. In addition to conventional hydrogen bonding and electrostatic interaction, amino residue Ala-576 was first identified to contribute to binding affinity through π-alkyl and alkyl interactions with the chlorinated substituent and aromatic ring. The selected compounds exhibited a high degree of safety in cytotoxicity tests against normal cells. Kinetic characterization of α-glucosidase inhibition confirmed a fully competitive inhibitory mode of action for these sulfonium salts. Full article

Soluble adenylyl cyclase (sAC) is molecularly and biochemically distinct from other mammalian nucleotidyl cyclases. It is uniquely regulated directly by bicarbonate (HCO₃⁻) and calcium (Ca²⁺) ions and is responsive to physiologic fluctuations in levels of its substrate, adenosine triphosphate (ATP). Our initial in vitro biochemical studies suggested two mechanisms for HCO₃⁻-dependent elevation of sAC activity: increasing catalytic rate and relieving inhibition observed in the presence of supraphysiological levels of substrate, ATP. Structural and mutational studies revealed that HCO₃⁻ increases catalytic rate via the disruption of a salt bridge that facilitates productive interactions with the substrate. Here, we demonstrate that the HCO₃⁻ stimulation observed under supraphysiological ATP concentrations is due to the mitigation of ATP-dependent acidification. Therefore, we conclude that the sole physiologically relevant mechanism of HCO₃⁻ regulation of sAC is through its pH-independent effect facilitating productive substrate binding to the catalytic site. Full article

The plant-specific PLATZ transcription factors play crucial roles in plant growth, development, and responses to abiotic stresses. However, despite their functional significance, PLATZ genes remain poorly characterized in soybeans. In this study, we conducted a genome-wide analysis of the GmPLATZ gene family and investigated their expression profiles under salt stress. We identified a total of 29 GmPLATZ genes in the soybean genome and systematically analyzed their physicochemical properties, conserved domains, evolutionary relationships, cis-acting elements, and expression regulation patterns. Subcellular localization predictions indicated nuclear localization for most GmPLATZs, except for GmPLATZ5 and GmPLATZ14, which showed dual chloroplast–nuclear localization. A gene family expansion analysis indicated that 21 segmental duplication events were the primary driver of GmPLATZ diversification. A phylogenetic analysis classified the GmPLATZ genes into four subgroups, while gene structure and motif analyses revealed conserved zinc-binding domains and identified multiple cis-acting elements associated with light responsiveness, hormone signaling, and stress responses. Expression profiling showed tissue-specific expression patterns, with 13 GmPLATZ genes differentially expressed under salt stress, including root-preferential members (e.g., GmPLATZ1, GmPLATZ10) and leaf-preferential members (e.g., GmPLATZ8, GmPLATZ9). This study provides a theoretical basis for further investigation of GmPLATZ gene functions in soybean development and stress tolerance. Full article

Tan sheep outperform Dorper sheep in meat-quality traits, including muscle fiber characteristics and fatty acid composition, while Dorper sheep excel in carcass weight. However, the molecular mechanisms underlying these breed-specific traits, especially gut microbiota–bile acid (BA) interactions, remain poorly understood. As host–microbiota co-metabolites, BAs are converted by colonic microbiota via bile salt hydrolase (BSH) and dehydroxylases into secondary BAs, which activate BA receptors to regulate host lipid and glucose metabolism. This study analyzed colonic BA profiles in 8-month-old Tan and Dorper sheep, integrating microbiome and longissimus dorsi muscle transcriptome data to investigate the gut–muscle axis in meat-quality and carcass trait regulation. Results showed that Tan sheep had 1.6-fold higher secondary BA deoxycholic acid (DHCA) levels than Dorper sheep (p < 0.05), whereas Dorper sheep accumulated conjugated primary BAs glycocholic acid (GCA) and tauro-α-muricholic acid (p < 0.05). Tan sheep exhibited downregulated hepatic BA synthesis genes, including cholesterol 7α-hydroxylase (CYP7A1) and 27-hydroxylase (CYP27A1), alongside upregulated transport genes such as bile salt export pump (BSEP), sodium taurocholate cotransporting polypeptide (NTCP), and ATP-binding cassette subfamily B member 4 (ABCB4), with elevated gut BSH activity (p < 0.05). DHCA was strongly correlated with g_Ruminococcaceae_UCG-014, ENSOARG00000001393, and ENSOARG00000016726, muscle fiber density, diameter, and linoleic acid (C18:2n6t) (|r| > 0.5, p < 0.05). In contrast, GCA was significantly associated with g_Lachnoclostridium_10, g_Rikenellaceae_RC9_gut_group, ENSOARG0000001232, carcass weight, and net meat weight (|r| > 0.5, p < 0.05). In conclusion, breed-specific colonic BA profiles were shaped by host–microbiota interactions, with DHCA potentially promoting meat quality in Tan sheep via regulation of muscle fiber development and fatty acid deposition, and GCA influencing carcass traits in Dorper sheep. This study provides novel insights into the gut microbiota–bile acid axis in modulating ruminant phenotypic traits. Full article

The Dof (DNA-binding with one finger) domain protein family is a plant-specific zinc finger transcription factor family that plays a role in various biological processes in plants. However, research on Dof transcription factors in soybean (Glycine max) remains limited. In this study, we identified 79 putative soybean Dof genes, which are distributed across the entire genome. A comparative phylogenetic analysis of the Dof gene family in soybean, Arabidopsis, rice, maize, and Medicago revealed five major groups. The synteny relationship analysis showed a large number of gene duplication events in soybean. Twelve cis-acting elements were detected in the promoter region of the Dof gene, including five hormone response elements and several environmental response elements. Expression pattern analysis indicated that most Gmdof genes exhibited specific expression patterns. Nine genes in group V, which exhibited higher expression in the root, were identified as significantly responsive to salt stress through qRT-PCR. The possible biological functions of several Gmdof genes were discussed, including Gmdof11.2, Gmdof2.1, and Gmdof16.2. In summary, this study integrated phylogenetic analysis with genome-wide expression profiling to provide valuable information for understanding the functional characteristics of Dof genes in soybean. Full article

Light-harvesting chlorophyll a/b-binding (Lhc) proteins are integral membrane proteins that bind to pigment molecules, playing a critical role in photosynthetic processes, including light energy harvesting and transfer. To investigate the role of the Lhc gene family in cucumber (Cucumis sativus L), genome-wide identification of CsLhc gene family members and analysis of their regulatory networks were carried out using bioinformation and molecular biology research methods at Anhui Science and Technology University. The results indicated that the Lhc family consisted of 21 members, being categorized into five subfamilies: Lhca, Lhcb, CP24, CP26, and CP29. The gene structure and motifs within each subfamily are generally conserved. CsLhcs are distributed on seven chromosomes, including one pair of tandem duplicates and two pairs of segmental duplicates. Six CsLhcs exhibit eight linear relationships with seven AtLhcs, and one CsLhc shows a syntenic relationship with one OsLhc. Analysis of the cis-acting elements in CsLhc promoters revealed their potential involvement in stress responses. Transcriptome data indicated that CsLhcs are minimally expressed in male flowers and roots, but highly expressed in other organs. Analysis of stress response processes revealed that all Lhc genes participate in at least one stress response. Five Lhc genes were confirmed to appear to have expression change using qPCR analysis under high temperature and salt stress. Particularly, under downy mildew, root-knot nematode stresses, and blight stress, up-regulated Lhc genes were the most abundant ones, indicating that the Lhc family acts as a significant role in the growth and development of cucumber. These results provide valuable insights for further understanding the characteristics of the CsLhc family and analyzing the function of the Lhc family in cucumber resistance to biotic/abiotic stresses and in molecular breeding. Full article

Background: Basic (region) leucine zippers (bZIPs) make up one of the largest families and are some of the most prevalent evolutionarily conserved transcription factors (TFs) in eukaryotic organisms. Plant bZIP family members are involved in seed germination, vegetative growth, flower development, light response, and various biotic/abiotic stress response pathways. Nevertheless, a detailed identification and genome-wide analysis of the bZIP family genes in broomcorn millet have not been conducted. Methods: In this research, we performed genome-wide identification, phylogenetic analysis, cis-elements analysis, and expression pattern analysis. Results: 144 bZIP transcription factors were identified from the P. miliaceum genome and classified into eleven subfamilies using a phylogenetic analysis. Motif and bZIP domain sequence alignment analyses indicated that the members in each subfamily were relatively conserved. Furthermore, a promoter analysis revealed that bZIP transcription factor family genes were responsive to multiple hormones and environmental stresses. Additionally, cis-element MYB binding sites were identified in the promoters of most PmbZIP genes. A gene expression analysis showed that 18 PmbZIP genes were differentially expressed during seed germination in salt stress, with 7 being significantly downregulated and 11 upregulated, thus suggesting that these PmbZIP genes may play an important role in the salt stress response and seed germination. Conclusions: Current research provides valuable information for further functional analyses of the PmbZIP gene family and as a reference for future studies on broomcorn millet’s stress response. Full article

This study introduces a newly synthesized Co(II) phthalocyanine complex (Co-Pc, 4) incorporating two (mercapto-terphenyl)thio-dione substituents, along with a detailed exploration of its structural, spectroscopic, and binding characteristics. The key precursor, 4-[(4′′-mercapto-[1,1′:4′,1′′-terphenyl]-4-yl)thio]phthalonitrile (compound 3), was first obtained and subsequently used to construct the phthalocyanine macrocycle through cyclotetramerization in the presence of cobalt and zinc salts under heat and vacuum in dimethylformamide. The resulting compounds (3 and 4) were characterized using a comprehensive array of analytical techniques, including elemental analysis, UV–Vis spectroscopy, FT-IR, ¹H-NMR, and Q-TOF mass spectrometry. Additionally, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were employed to elucidate the electronic structure and geometrical features of Co-Pc 4, providing theoretical support for the experimental findings. The integration of theoretical and experimental findings provides in-depth insight into the electronic behavior and reactivity of compound 4, highlighting its promise as a candidate for photovoltaic applications. Further studies may investigate how structural modifications influence these properties, potentially leading to improved device performance. Full article

Pharmaceuticals, such as the antibiotic erythromycin, and sodium-dependent glucose transporter (SGLT1 & SGTL2) inhibitors such as Bexagliflozin (diabetes) and Sotagliflozin (heart disease), are often sugar-decorated (glycosylated). Glycosylation is a key component of the binding motif in SGLT inhibitors and, in natural products, glycosylation often confers improved bioactivity and bioavailability. Whilst a single C-glycoside link between a sugar moiety and its aglycone core is a common feature in natural products isolated to date, only a small number, including the antibiotics granaticin and sarubicin, are covalently bonded twice to a single sugar moiety. The way in which this “double C-glycosylation” is naturally mediated is not yet known, yet has been speculated on. Here, we report the exploration and development of a potentially biomimetic procedure that utilises intermolecular cycloaddition chemistry to access new “double C-glycosylated” products and enables the creation of bridged polycyclic ethers from a common maltol-derived oxidopyrylium salt precursor. Full article

This study investigated the synergistic effects of ultra-high pressure (UHP) and egg white protein (EWP) on the gel properties of sodium-reduced shrimp surimi. A Box–Behnken design targeting UHP pressure (200–400 MPa), duration (10–20 min), and EWP/myofibrillar protein (MP) ratio (1:9–5:5) was implemented to optimize gel strength, water holding capacity (WHC), and whiteness. Optimal conditions (290 MPa/15 min/EWP:MP = 3:5) yielded the following validated improvements, versus conventional processing: 282.27 g·mm gel strength, 14.90% WHC enhancement, and 16.63% reduced cooking loss. Texture profile analysis demonstrated superior elasticity in composite gels. Magnetic resonance imaging and scanning electron microscopy revealed a denser microstructure with enhanced water-binding capacity, corroborated by the rheological evidence of strengthened viscoelasticity. UHP promotes the partial expansion of MP, exposing hydrophobic groups and sulfhydryl groups, thereby enhancing intermolecular interactions. It also promotes the expansion of EWP, enabling the formation of disulfide bonds between molecules and facilitating the formation of network structures. These findings propose a scalable strategy for developing clean-label salt-reduced aquatic surimi products. Full article