Search Results (3,781)

The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn¹³⁹ in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His⁶¹, Asp¹⁰⁹, and Ser²⁰⁴) and substrate-binding residues (Asp¹⁹⁸, Ser²¹⁹, and Gly²²¹), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article

The detection of trace chemicals at low and ultra-low concentrations is critical for applications in environmental monitoring, medical diagnostics, food safety and other fields. Conventional detection techniques often lack the required sensitivity, specificity, or cost-effectiveness, making real-time, in situ analysis challenging. Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical tool, offering improved sensitivity through the enhancement of Raman scattering by plasmonic nanostructures. While noble metals such as Ag and Au are currently the reference choices for SERS substrates, fabrication methods should balance enhancement efficiency, reproducibility and scalability. In this study, we propose a novel approach for SERS substrate fabrication using reactive Aerosol Jet Printing (r-AJP) as an innovative additive manufacturing technique. The r-AJP process enables in-flight Ag seed reduction and nucleation of Ag nanoparticles (NPs) by mixing silver nitrate and ascorbic acid aerosols before deposition, as suggested by computational fluid dynamics (CFD) simulations. The resulting coatings were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses, revealing the formation of nanoporous crystalline Ag agglomerates partially covered by residual matter. The as-prepared SERS substrates exhibited remarkable SERS activity, demonstrating a high enhancement factor (10⁶) for rhodamine (R6G) detection. Our findings highlight the potential of r-AJP as a scalable and cost-effective fabrication strategy for next-generation SERS sensors, paving the way for the development of a new additive manufacturing tool for noble metal material deposition. Full article

The Varnous Mt. area in the northern Pelagonian Nappe is characterized by the intrusion of an Early Permian pluton, with its tectonic setting and igneous petrology well constrained in earlier studies. The metamorphic basement rocks warrant further detailed investigation due to their complex history. These rocks are polymetamorphosed, preserving a sequence of overprinting metamorphic and deformational events. The metapelitic rocks have undergone an initial, pre-Carboniferous regional metamorphism of unknown grade before or during Hercynian Orogeny, followed by a thermal metamorphic event associated with the intrusion of the Varnous pluton at 297 Ma. The assemblage attributed to this event is And + Crd + Bt + Ms (west), while the first assemblage identified at the eastern part is Sil + Bt + Gt. Additionally, three regional tectonometamorphic events occurred during the Alpine Orogeny. For the Alpine events, the assemblages are as follows: first, the development of St + Gt + Chl + Kfs + Pl + Qtz at 150–130 Ma; second, retrograde metamorphism of these assemblages with Cld + Gt + Ser + Mrg + Chl ± Sil (Fi) at 110–90 Ma; and finally, mylonitization of all previous assemblages at 90–70 Ma with simultaneous annealing and formation of Cld + Chl + Ms. Full article

Resveratrol (RSV), a polyphenol found in a variety of berries and wines, is known for its anti-inflammatory, anticancer, and antioxidant properties. It has been suggested that RSV may play a role in the regulation of metabolic disorders, including diabetes and insulin resistance. However, in recent years, it has been reported to completely inhibit Akt kinase function in liver cells. Akt is a central protein involved in the metabolic function of insulin and is regulated by the phosphatidylinositol-3-kinase (PI3K) pathway. In this study, we examined the effect of RSV on insulin-induced insulin receptor (IR) phosphorylation and proteins involved in the PI3K/Akt pathway in a hepatic cell model, clone 9 (C9), and in hepatoma cells, Hepa 1-6 (H1-6). In both cell lines, RSV inhibited tyrosine phosphorylation of IR and insulin-induced activation of Akt. We also evaluated the effect of RSV on the activation of protein tyrosine phosphatase 1B (PTP1B), which is associated with IR dephosphorylation, and found that RSV increased PTP1B-Tyr¹⁵² phosphorylation in a time- and concentration-dependent manner. Furthermore, we found that the protein kinase C (PKC) inhibitors BIM and Gö6976 prevented the inhibition of Akt phosphorylation by RSV and increased the phosphorylation of Ser/Thr residues in IR, suggesting that PKC is involved in the inhibition of the insulin pathway by RSV. Thus, classical PKC isoforms impair the PI3K/Akt pathway at the IR and GSK3 and GS downstream levels; however, IRS-Tyr⁶³² phosphorylation remains unaffected. These results suggest that RSV can lead to insulin resistance by activating PTP1B and PKC, consequently affecting glucose homeostasis in hepatic cells. Full article

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

Chiral molecules are crucial in the field of optical devices, molecular recognition, and other novel functional materials due to their unique spatially asymmetric configuration and optical activity. In this study, a chiral molecule, Cholest-3-yl (E)-3-(4-carbamoylphenyl)acrylate (CCA), was combined with dyes containing large conjugated structures, tetramethylporphyrin tetrasulfonic acid (TPPS), and Nickel(II) phthalocyanine-tetrasulfonic acid tetrasodium salt (TsNiPc), and composite LB films of CCA/TPPS and CCA/TsNiPc were successfully prepared by using Langmuir-Blodgett (LB) technology. The circular dichroism (CD) test proved that the CCA/TPPS composite film had a strong CD signal at 300–400 nm, and the composite film showed chirality. This significant optical activity provides a new idea and option for the application of LB films in chiral sensors. In the Surface Enhanced Raman Spectroscopy (SERS) test, the CCA/TPPS composite film was sensitive to signal sensing, in which the enhancement factor EF = 2.28 × 10⁵, indicating that a large number of effective signal response regions were formed on the surface of the film, and the relative standard deviation (RSD) = 12.08%, which demonstrated that the film had excellent uniformity and reproducibility. The high sensitivity and low signal fluctuation make the CCA/TPPS composite LB film a promising SERS substrate material. Full article

Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF patients undergoing in vitro fertilization, stratified by FSHR (follicular stimulating hormone receptor) genotype Asn680Ser with or without GH supplementation. Patients were stratified by FSHR genotype into homozygous Ser/Ser versus Ser/Asn or Asn/Asn groups. Overall, GH co-treatment conferred modest benefits in the unselected RIF cohort, limited to a higher cumulative live birth rate compared to controls and elevated leukemia inhibitory factor (LIF) levels (p < 0.05 both). When stratified by FSHR genotype, the Ser/Ser subgroup exhibited markedly better outcomes with GH. These patients showed a higher (0.5 vs. 0.33, p = 0.003), produced more embryos (2.88 vs. 1.53, p = 0.02), and had a markedly improved cumulative live birth rate—50% with GH versus 13% without—highlighting a clinically meaningful benefit of GH in the Ser/Ser subgroup. No significant benefit was observed in Asn allele carriers. These findings suggest that FSHR genotyping may help optimize treatment selection in RIF patients by identifying those most likely to benefit from GH supplementation. Full article

Pesticide residues in fruits and vegetables pose a serious threat to food safety. Traditional detection methods have defects such as complex operation, high cost, and long detection time. Therefore, it is of great significance to develop rapid, non-destructive, and efficient detection technologies and equipment. In recent years, the combination of spectroscopic techniques and imaging technologies with machine learning algorithms has developed rapidly, providing a new attempt to solve this problem. This review focuses on the research progress of the combination of spectroscopic techniques (near-infrared spectroscopy (NIRS), hyperspectral imaging technology (HSI), surface-enhanced Raman scattering (SERS), laser-induced breakdown spectroscopy (LIBS), and imaging techniques (visible light (VIS) imaging, NIRS imaging, HSI technology, terahertz imaging) with machine learning algorithms in the detection of pesticide residues in fruits and vegetables. It also explores the huge challenges faced by the application of spectroscopic and imaging technologies combined with machine learning algorithms in the intelligent perception of pesticide residues in fruits and vegetables: the performance of machine learning models requires further enhancement, the fusion of imaging and spectral data presents technical difficulties, and the commercialization of hardware devices remains underdeveloped. This review has proposed an innovative method that integrates spectral and image data, enhancing the accuracy of pesticide residue detection through the construction of interpretable machine learning algorithms, and providing support for the intelligent sensing and analysis of agricultural and food products. Full article

In recent years, most of the populations of the world have been using herbal materials for their strong antimicrobial properties and major health benefits. The objective of this study was to evaluate the phenolic profile, as well as the antioxidant and antimicrobial activities, of a dietary supplement composed of extracts from hibiscus (Hibiscus sabdariffa L.) calyces and lemon verbena (Lippia citriodora) leaves (Metabolaid^®, Patent P201731147) mixed at a weight ratio of 35:65 (w/w), respectively. The bioactive components of the methanolic extract were analyzed by UHPLC-ESI-MS/MS. The antioxidant activity was evaluated using spectrophotometric methods, while the antimicrobial activity was assessed through the microdilution method against selected Gram-negative and Gram-positive bacteria. The total phenols content resulted in being 256.10 ± 2.26 mg GAE/g f.w., the flavonoid content was 48.90 ± 2.95 mg CE/g f.w., flavonols were 60.17 ± 7.68 mg QE/g f.w., and anthocyanins were 3.78 ± 0.17 mg C3GE/g f.w. The FRAP value, observed in the natural mix additive, was 1.25 ± 0.03 mg Fe²⁺/g f.w., while the ORAC showed the value of 1893.77 ± 30.39 µmol TE/g f.w. and the DPPH was 23.33 ± 4.12 µg/mL. We found eight phenolic acids, seven flavonols, five anthocyanins, and nine other phenolic compounds. The extract showed a minimum inhibitory concentration (MIC) of 12.5 mg/mL against E. coli, E. aerogenes, and E. faecalis and of 25 mg/mL against S. enterica ser. Typhimurium and S. aureus and a minimum bactericidal concentration (MBC) of 25 mg/mL against E. coli, E. aerogenes, and E. faecalis and of 50 mg/mL against S. enterica ser. Typhimurium and S. aureus. In conclusion, our findings demonstrate that Metabolaid^® is a rich source of bioactive compounds and provides beneficial effects against oxidative stress and pathogenic bacteria, supporting its nutraceutical potential. Full article

Background: Obesity is associated with insulin resistance (IR) and characterized by impaired activation of the PI3K/AKT route and glucose uptake. Elevated plasma levels of palmitic acid (PA) diminish insulin signaling in vitro and in vivo. Origanum vulgare L. essential oil (OVEO) is rich in monoterpenes with protective effects against IR. Objective: The study aimed to assess total phenols content and antioxidant activity of OVEO and its cytotoxicity, as well as its effect on insulin signaling and glucose uptake in PA-treated adipocytes. Methods: The quantification of total phenolic content was determined using the Folin–Ciocalteu method, while the antioxidant capacity of OVEO was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The cytotoxicity of OVEO (0.1–10 µg/mL) was assessed using the MTS assay. SW872 adipocytes were incubated with 0.4 mM PA for 24 h, with or without a 2 h preincubation of OVEO, and then stimulated with insulin (100 nM, 10 min) or a vehicle. Phosphorylation of Tyr-IRS-1, Ser-AKT, and Thr-AS160 was analyzed by Western blot, and glucose uptake was measured using 2-NBDG. Results: OVEO contained phenols and exhibits antioxidant capacity. All the concentrations of OVEO assessed were not cytotoxic on SW872 adipocytes. PA decreased basal phospho-AS160 as well as insulin-stimulated phospho-IRS1, phospho-AKT, phospho-AS160 and glucose uptake, while OVEO co-treatment enhanced these markers. Conclusions: These findings suggest a beneficial effect of OVEO on the PA-impaired insulin pathway and glucose uptake, which might be explained by its phenolic content and antioxidant capacity, highlighting its potential as a complementary therapeutic agent for IR and related metabolic disorders. Full article

The coffee-ring effect, while harnessed in diverse fields such as biosensing and printing, poses challenges for achieving uniform particle deposition. Controlling this phenomenon is thus essential for precision patterning. This study proposes a novel method to regulate coffee-ring formation by tuning surface wettability via integrated nanoporous and hexagonal microstructures. Four distinct surface types were fabricated using UV nanoimprint lithography: planar, porous planar, hexagonal wall, and porous hexagonal wall. The evaporation behavior of colloidal droplets and subsequent particle aggregation were analyzed through contact angle measurements and confocal microscopy. Results demonstrated that nanoscale porosity significantly increased surface wettability and accelerated evaporation, while the hexagonal pattern enhanced droplet stability and suppressed contact line movement. The porous hexagonal surface, in particular, enabled the formation of connected dual-ring patterns with higher particle accumulation near the contact edge. This synergistic design facilitated both stable evaporation and improved localization of particles. The findings provide a quantitative basis for applying patterned porous surfaces in evaporation-driven platforms, with implications for enhanced sensitivity and reproducibility in surface-enhanced Raman scattering (SERS) and other biosensing applications. Full article

Lindane, a persistent organochlorine pesticide, exerts toxic effects on the female reproductive system, compromising oocyte quality and maturation. However, the effects of this pesticide on mammalian oocyte morphology and ultrastructure remain unknown. This study investigated the effects of Lindane on mouse oocyte ultrastructure using an in vitro model with Transmission Electron Microscopy (TEM) at concentrations from 1 to 100 μM. The results revealed a progressive dose-related trend of alterations: at 1 μM, mild swelling of smooth endoplasmic reticulum (SER) vesicles; at 10 μM, increased SER dilation and cytoplasmic disorganization; and at 100 μM, pronounced vacuolization, mitochondrial swelling, dense lamellar bodies (dlbs), and multivesicular bodies (MVBs) indicative of autophagic activity. Mitochondrial alterations increased significantly with concentration: 3.2 ± 0.8 (control), 5.7 ± 1.0 (1 μM), 9.4 ± 1.5 (10 μM), and 16.8 ± 2.3 (100 μM) altered mitochondria per oocyte (p < 0.01). Vacuole frequency was notably elevated at 100 μM (4.3 ± 1.1 vs. 0.7 ± 0.5 in controls), and mislocalization of organelles within the ooplasm was observed. In conclusion, Lindane-induced oocyte ultrastructural alterations were observed at all tested concentrations but were more pronounced at 100 μM. These results highlight its impact on female fertility and may guide the search for protective agents, as well as efforts to reduce environmental exposure to endocrine disruptors. Full article

This pilot study investigated the metabolic responses of five selected bacteria to physiological stress. Surface-enhanced Raman spectroscopy was used to analyze spectral changes associated with the release of adenine, a key metabolite indicative of stress conditions. Laboratory-synthesized spherical silver and gold nanoparticles, which remained stable over an extended period, were employed as enhanced surfaces. Bacterial cultures were analyzed under standard conditions and in the presence of a selected stressor—demineralized water—inducing osmotic stress. The results showed that the adenine signal originated from metabolites released into the surrounding environment rather than directly from the bacterial cell wall. The study confirms the suitability of these cost-effective and easily synthesized stable nanoparticles for the qualitative detection of bacterial metabolites using a commercially available Raman instrument. Full article

Exosomes are nanoscale extracellular vesicles (EVs) that carry biomolecular signatures reflective of their parent cells, making them powerful tools for non-invasive diagnostics and therapeutic monitoring. Despite their potential, clinical application is hindered by challenges such as low abundance, heterogeneity, and the complexity of biological samples. To address these limitations, plasmonic biosensing technologies—particularly propagating surface plasmon resonance (PSPR), localized surface plasmon resonance (LSPR), and surface-enhanced Raman scattering (SERS)—have been developed to enable label-free, highly sensitive, and multiplexed detection at the single-vesicle level. This review outlines recent advancements in nanoplasmonic platforms for exosome detection and profiling, emphasizing innovations in nanostructure engineering, microfluidic integration, and signal enhancement. Representative applications in oncology, neurology, and immunology are discussed, along with the increasingly critical role of artificial intelligence (AI) in spectral interpretation and diagnostic classification. Key technical and translational challenges—such as assay standardization, substrate reproducibility, and clinical validation—are also addressed. Overall, this review highlights the synergy between exosome biology and plasmonic nanotechnology, offering a path toward real-time, precision diagnostics via sub-femtomolar detection of exosomal miRNAs through next-generation biosensing strategies. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article