Search Results (337)

Tylorrhynchus heterochaetus is an aquatic food with both edible and medicinal value in China. With a protein-rich body wall, it has strong potential for producing bioactive peptides. To explore its potential as a source of immunomodulatory peptides, in this study, flavor enzymes were selected as the optimal hydrolases, and the hydrolyzed products were subjected to ultrafiltration fractionation. The <3000 Da portion exhibited the most effective immune-stimulating activity in RAW 264.7 macrophages, enhancing phagocytosis and promoting the secretion of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) in a concentration dependent manner. Peptide omics analysis, combined with the activity and safety screened by bioinformatics, identified 43 candidate peptides. Molecular docking predicts that three novel peptides, LPWDPL, DDFVFLR and LPVGPLFN, exhibit strong binding affinity with toll-like receptor 4/myeloid differentiation factor-2 (TLR4/MD-2) receptors through hydrogen bonding and hydrophobic/π stacking interactions. Synthetic verification confirmed that these peptides were not only non-toxic to cells at concentrations ranging from 62.5 to 1000 µg/mL, but also effective in activating macrophages and stimulating the release of immune mediators. This study successfully identified the specific immunomodulatory peptides of the Tylorrhynchus heterochaetus, supporting its high-value utilization as a natural source of raw materials for immunomodulatory functional foods. Full article

Objectives: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) commonly relies on somatostatin receptor subtype 2 (SSTR2) agonists such as DOTA-TOC/TATE, which may show limited efficacy due to high hepatic uptake and therapy resistance in some patients. SSTR2 antagonists have demonstrated superior tumor targeting. This study aimed to establish the production and quality control of the Actinium-225-labeled SSTR2 antagonist [²²⁵Ac]Ac-DOTA-LM3 and to report in-human clinical experience with targeted alpha therapy (TAT). Methods: [²²⁵Ac]Ac-DOTA-LM3 was produced by radiolabeling DOTA-LM3 with Actinium-225 under validated conditions. Radiochemical conversion, purity, yield, and stability were assessed using radio-TLC, fractionated radio-HPLC combined with gamma spectroscopy, and in vitro serum stability testing. Clinical feasibility and therapeutic response were evaluated in a patient with metastatic neuroendocrine pancreatic neoplasm refractory to prior ¹⁷⁷Lu-based PRRT. Results: Radiolabeling achieved reproducibly high radiochemical purity (>97%) and decay-corrected yields exceeding 80%. The radiopharmaceutical showed high in vitro stability with minimal release of free Actinium-225 over five days. Fractionated radio-HPLC enabled indirect purity assessment. In the reported patient, [²²⁵Ac]Ac-DOTA-LM3 therapy resulted in partial remission without clinically relevant hematologic, renal, or hepatic toxicity and was associated with marked clinical improvement. Conclusions: [²²⁵Ac]Ac-DOTA-LM3 can be produced with high purity and stability using clinically applicable procedures. In-human results suggest promising efficacy and safety, supporting further clinical investigation of Actinium-225-labeled SSTR2 antagonists for advanced NETs. Full article

Arid and semi-arid soils represent extreme habitats where microbial life is constrained by high temperature, low water availability, salinity, and nutrient limitation, yet these ecosystems harbor unique bacterial communities that sustain key ecological processes. To explore the diversity and functional potential of prokaryotic assemblages in Algerian drylands, we compared soils from three contrasting sites: The Oasis of Djanet (RM1), the hyper-arid Tassili of Djanet desert (RM2), and the semi-arid El Ouricia forest in Sétif (RM3). Physicochemical analyses revealed strong environmental gradients: RM2 exhibited the highest pH (8.66), electrical conductivity (11.7 dS/m), and sand fraction (56%), whereas RM3 displayed the greatest moisture (10.9%), organic matter (7.6%), and calcium carbonate (20.7%) content, with RM1 generally showing intermediate levels. High-throughput 16S rRNA gene sequencing generated >60,000 effective reads per sample with sufficient coverage (>0.99). Alpha diversity indices indicated the highest bacterial richness and diversity in RM2 (Chao1 = 3144, Shannon = 10.0), while RM3 showed lower evenness and the dominance of a few taxa. Across sites, 66 phyla and 551 genera were detected, dominated by Actinobacteriota (38–45%) and Chloroflexi (13–44%), with Proteobacteria declining from RM1 (17.5%) to RM3 (3.3%). Venn analysis revealed limited overlap, with only 58 operational taxonomic units shared among all sites, suggesting highly habitat-specific communities. Predictive functional profiling (PICRUSt2, Tax4Fun, FAPROTAX) indicated metabolism as the dominant functional category (≈50% of KEGG Level-1), with carbohydrate and amino acid metabolism forming the metabolic backbone. Notably, transport functions (ABC transporters), lipid metabolism, and amino acid degradation pathways were enriched in RM2–RM3, consistent with adaptation to osmotic stress, nutrient limitation, and energy conservation under aridity. Collectively, these findings demonstrate that Algerian arid and semi-arid soils host diverse, site-specific bacterial communities whose functional repertoires are strongly shaped by soil chemistry and climate, highlighting their ecological and biotechnological potential. Full article

Ensuring good air quality in indoor environments of historical and artistic significance is essential not only for protecting valuable artworks but also for safeguarding human health. While many studies in this field tend to focus on the preservation of cultural heritage, fewer have addressed the impact on visitors and worshippers. Yet, places such as museums, galleries, churches, and other religious sites attract large numbers of people, making indoor air quality a key factor for their well-being. This study focused on evaluating air quality within the Santuario della Beata Vergine dei Miracoli in Saronno, Italy, a religious site that welcomes large numbers of visitors and worshippers each year. A detailed analysis of particulate matter was conducted, including chemical characterization by ICP-MS for metals, ion chromatography for water-soluble ions, and thermal–optical analysis for the carbonaceous fraction, as well as assessments of size distribution and radiometric properties. The results indicated overall good air quality conditions: concentrations of heavy metals were below levels of concern (<35 ng m⁻³), and gross alpha, beta, and ¹³⁷Cs activity concentrations remained below the minimum detectable thresholds. Hence, no significant health risks were identified. Full article

Alzheimer’s disease (AD) is marked by cognitive decline, and also by retinal degeneration. Having in mind that docosahexaenoic acid (DHA, 22:6n − 3) is a safe, low-cost, and pivotal fatty acid for brain health and sustained cognitive function, this study exploits environmentally friendly non-fish sources as potential dietary supplements enriched with DHA to prevent or reverse AD. Forty 5xFAD transgenic male mice, aged five weeks old, were randomly distributed by five body weight-matched dietary groups (with eight animals each) and fed isocaloric diets based on the AIN-93M standard formulation for rodents for 6 months. Except for the control feed (without supplementation), each diet contained a modified lipidic fraction supplemented with 2% of the following: (1) linseed oil (LSO, rich in alpha-linolenic acid (ALA, 18:3n − 3)); (2) cod liver oil (fish oil, FO, rich in both DHA and eicosapentaenoic acid (EPA, 20:5n − 3)); (3) Schizochytrium sp. microalga oil (Schizo, with 40% of DHA); and (4) commercial DHASCO (DHASCO, with 70% of DHA). The aim of this study was to measure retinal neural layer thickness, calculate ganglion cell layer (GCL) density, and assess retinal injury by means of immunohistochemical staining for β-amyloid plaques deposition, TAU protein levels, and IBA1, as hallmark features of AD progression, in order to elucidate the effects of different dietary DHA treatments in Alzheimer’s retinas. Although no statistical differences were observed across retinal layer thicknesses depending on the diet (p > 0.05), there was a consistent pattern for slightly increased retinal thickness in 5xFAD mice fed fish oil relative to the others for the measurement of total layers, in general and for the inner segment/outer segment layer, the outer nuclear layer, the outer plexiform layer, the inner nuclear layer, and the inner plexiform layer, in particular. The ganglion cell layer (GCL) density was increased in 5xFAD mice fed the DHASCO oil diet relative to the control (p < 0.05), suggesting a benefit of DHA supplementation on the number of viable ganglion cells. No positive staining was observed for β-amyloid plaques deposition or the neuroinflammatory marker, IBA1, corroborating previous findings in human AD retinas. Conversely, the internal retinal layers showed intense TAU immunostaining. Immnunostained TAU area was significantly reduced in 5xFAD mice fed a fish oil diet compared to control (p < 0.05), although the number of TAU-positive cells did not differ across diets (p > 0.05). The retinal protected integrity derived from the benefits of DHA supplementation found, either from fish oil or DHASCO oil, underscores the potential of retinal biomarkers as non-invasive indicators of cognitive decline and overall brain health, opening new avenues for investigating AD pathophysiology in the retina. Full article

Objectives: This study investigates the effects of resveratrol on systemic inflammatory, oxidative, and metabolic responses in a rat model that combines surgical trauma with prior exposure to Single Prolonged Stress (SPS), an established experimental protocol for modeling post-traumatic stress disorder (PTSD). Methods: Male Wistar rats (n = 21) were randomly assigned to three groups: (I) control (polyvinylpyrrolidone, PVP), (II) SPS + laparotomy + PVP), and (III) SPS + laparotomy + resveratrol. Resveratrol (5 mg/kg of body weight/day) or vehicle was administered intragastrically for seven days. Serum concentrations of cortisol, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), glucose, insulin, lipid fractions, and thiobarbituric acid–reactive substances (TBA-RS) were determined by enzyme-linked immunosorbent assay and spectrophotometric methods. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Results: Combined SPS and surgical trauma induced a pronounced systemic inflammatory response characterized by elevated cortisol (+138%), TNF-α (+83%), IL-6 (+465%), and ceruloplasmin (+71%), as well as hyperglycemia, hyperinsulinemia, increased HOMA-IR, and atherogenic dyslipidemia with reduced high-density lipoprotein cholesterol (HDL-CH; −64%), elevated triglycerides (TGs; +216%), and very low-density lipoprotein cholesterol (VLDL-CH; +218%). Marked activation of lipid peroxidation was observed, as indicated by increased TBA-RS levels before and after incubation. Resveratrol administration significantly decreased cortisol (−45%), TNF-α (−47%), and IL-6 (−85%), normalized the IL-10/IL-6 ratio, and reduced ceruloplasmin levels (−13%). The compound improved insulin sensitivity (HOMA-IR −50%), elevated HDL-CH (+115%), and lowered TGs and VLDL-CH (−44%). It also attenuated both basal and inducible lipid peroxidation (TBA-RS −11% and −13%), indicating restoration of antioxidant capacity. Conclusions: Thus, resveratrol effectively counteracts the neuroendocrine, inflammatory, and metabolic disturbances induced by combined PTSD-like stress and surgical trauma. Full article

Soil microbial communities are vital for saline-alkaline ecosystem functioning; however, their succession during land degradation and their influence on phosphorus (P) transformation remain unclear. To address this gap, this study investigated the dynamics of soil microbial communities and P fractions along a degradation gradient from native grassland to Suaeda salsa vegetation and ultimately to bare land in the Songnen Plain, China. The results revealed that progressive saline-alkaline degradation significantly altered soil properties, increased the proportion of stable P fractions, and reduced microbial alpha diversity. Network analysis revealed that bacterial communities shifted from competition to cooperation along the salinity–alkalinity degradation gradient, indicating a cooperative strategy to cope with environmental stress. Fungal networks exhibit progressively reduced complexity and stability with increasing degradation. Partial least squares path modeling confirmed that soil pH and electrical conductivity directly and indirectly regulated P fractions by reshaping microbial communities, with bacteria exhibiting a stronger total effect than fungi. In conclusion, saline-alkaline degradation drives microbial community succession, which mediates the transformation of soil P into more stable forms and exacerbates P limitation. This study provides a scientific basis for targeted restoration and sustainable management of saline-alkaline ecosystems. Full article

Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary condition caused by the duplication of the PMP22 gene. Overexpression of peripheral myelin protein 22 in Schwann cells leads to myelin sheath defects and axonal loss. We have produced a cell model to facilitate studies of the molecular mechanisms involved in PMP22 accumulation and clearance. Our model is a stably transfected, clonal, immortalised human Schwann cell line with overexpressed levels of PMP22 fusion protein. A control-transfected cell line (vector lacking PMP22) was also produced. PMP22-transfected cells had reduced levels of mitosis, with the PMP22 fusion protein concentrated in punctate aggregates in the cytoplasm and expressed at the plasma membranes, which were often irregular and spindly. In contrast, control cells (control-transfected and parent cell lines) generally had smooth and regular plasma membrane morphology. Culturing in the presence of NRG1 and forskolin lead to upregulation of markers of myelination potential in the control cells. These markers were more variable in the cells stably transfected with PMP22, including decreased levels of transcripts of SOX10, JUN, S100B and NGFR, but increased levels of MPZ and EGR2 compared to controls. Using proximity-dependent biotin identification (BioID2), several hundred proteins were identified in the proximity of the overexpressed PMP22, of which 291 significant proteins were only detected in the proximity of PMP22 and not in that of control pull-downs. Among the most significantly enriched PMP22-interacting proteins were integrins alpha-2 (ITGA2) and alpha-7 (ITGA7), which play a role in myelination via their interactions with the extracellular matrix. The presence of ITGA2 in just the PMP22-transfected fraction was confirmed by western blot. Some of the proteins were associated with several enriched molecular pathways, including molecular transport and protein trafficking, and may represent potential therapeutic targets for CMT1A by promoting the degradation and enhanced trafficking of PMP22. Full article

Ovarian cancer (OC) is usually diagnosed at an advanced stage, contributing to its high mortality rate. The presence of concurrent bacterial infections in these patients is a common clinical observation, and the mechanisms by which this coinfection influences tumor progression are still not fully understood. This study investigates the role of polydisperse extracellular vesicles (PEVs) secreted by OC cells in response to bacterial components, aiming to elucidate a potential communication pathway between OC and the bacterial microenvironment. We stimulated a human OC cell line in vitro with a fraction of E. coli. Our results show that this bacterial stimulation significantly increases the secretion of PEVs by cancer cells. A subsequent proteomic analysis of these PEVs revealed an enrichment of proteins, including filamin A, filamin B, alpha-enolase, and heat shock cognate 71 kDa protein. In addition, the PEVs displayed protease activity (on fibronectin and gelatin) and phosphatase activity against para-nitrophenyl phosphate, indicating their capacity to alter cellular signaling. This represents a novel mechanism through which bacterial coinfection may influence the biological behavior of OC if bacteria interact with tumor cells, potentially contributing to their aggressiveness and the challenges associated with their treatment. Our work highlights the importance of studying the interplay between the tumor and its associated microbiota to better understand ovarian cancer progression and identify new therapeutic targets. Full article

Sea mayweed (Tripleurospermum maritimum L. syn. Matricaria maritima) is a halophytic species widely distributed along the Atlantic shoreline. Unlike other Tripleurospermum species, the chemical composition and biological activities of this halophyte have received no attention. Here, a hydroalcoholic extract of sea mayweed leaves was evaluated for in vitro antioxidant (DPPH, ABTS, and FRAP bioassays), anti-inflammatory (NO reduction in RAW 264.7 macrophages), anti-diabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin protective (tyrosinase, melanogenesis, elastase, and collagenase inhibition) activities. Solid–liquid partition chromatography of the extract and NMR characterization of its fractions allowed the identification of some major compounds, including fructo-oligosaccharides in the MeOH_20% fraction, a new carbohydrate called tripleurospermine (1), 3-5-dicaffeoylquinic acid (2) in the MeOH_40% fraction, and matricaria lactone (3) in the MeOH_80% fraction. MeOH₄₀ fraction exhibited strong antioxidant, anti-tyrosinase (thus skin-whitening potential), and anti-glycosidase activities (anti-diabetic potential), whereas MeOH_80% fraction showed anti-inflammatory and anti-diabetic potential. Overall, our results suggest that sea mayweed may have dietary or medicinal uses due to its biochemical composition and bioactivities. Full article

To enhance the nutritional value of sheep fat, high-melting-point solid fat (HSO) and low-melting-point liquid oil (LSO) were prepared from Altay sheep rump fat via solvent fractionation. The effects of HSO and LSO on lipid metabolism and intestinal health were evaluated in a mouse model. Results showed that HSO, rich in saturated fatty acids (SFA), induced obesity, dyslipidemia, and colonic inflammation in mice. These adverse effects were associated with the upregulation of hepatic lipid synthesis genes such as Sterol regulatory element-binding protein 1c (SREBP-1c) and Fatty acid synthase (FAS), as well as increased expression of pro-inflammatory cytokines including Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the colon. In contrast, LSO, which was predominantly composed of unsaturated fatty acids (UFA), did not cause significant metabolic disorders. Instead, it promoted the upregulation of fatty acid oxidation-related genes such as Peroxisome proliferator-activated receptor alpha (PPARα) and Acyl-CoA oxidase 1 (Acox1), helped maintain intestinal microbial balance, and enhanced the production of beneficial short-chain fatty acids (SCFAs), particularly butyrate and propionate. In conclusion, solvent fractionation effectively modulates the fatty acid composition of sheep fat, thereby influencing lipid metabolism and inflammatory responses through the regulation of key gene expression and modulation of the gut microenvironment. Full article

Electroencephalography (EEG) provides a powerful means of capturing real-time neural activity, enabling the study of cognitive processes during complex learning tasks. This study explores the application of wearable EEG and advanced signal analysis to examine cognitive profiles of 30 sixth-grade students engaged in fraction learning. Using validated estimations alongside interactive digital tools such as Fraction Lab and the Diamond Paper task, EEG recordings were processed to evaluate spectral dynamics across delta, theta, alpha, and beta bands. Results revealed that lower-performing students exhibited elevated delta and theta power under cognitive load, whereas higher-performing students showed more stable beta activity linked to cognitive control. These findings highlight the utility of EEG-based signal analysis for identifying neurocognitive markers associated with conceptual and procedural knowledge (PK) in mathematics. The integration of such methodologies supports the development of precision-oriented educational strategies grounded in objective neural data. Clustering further revealed three learner profiles: Core Support Needed, Developing, and Advanced, while classification analyses confirmed that EEG features, especially gamma and beta oscillations, reliably distinguished among them, underscoring the potential of neurocognitive markers to guide adaptive instruction. Full article

α-CGRP (alpha-calcitonin gene-related peptide) is a vasoactive and anti-inflammatory neuropeptide that is cardioprotective in transverse aortic constriction (TAC)-induced pressure overload heart failure (HF) models. Our previous investigations established that a peptoid modification of α-CGRP, termed NMEG-CGRP, prevented left ventricular (LV) dysfunction and remodeling when administered subcutaneously every other day for 28 days, starting two days post-TAC surgery (termed prevention study). Here, we determined whether NMEG-CGRP would be cardioprotective when administered after the development of LV dysfunction secondary to TAC surgery (termed treatment study). Starting 15 days post-sham or TAC surgery, we administered NMEG-CGRP (3.6 mg/kg/mouse) subcutaneously every other day for 28 days in mice assigned to treatment groups. In vivo assessments included weekly electrocardiography to evaluate cardiac function and blood sampling for immunophenotyping. On Day 45, mice were euthanized, and hearts were collected for gross, histological, and biochemical analyses. Compared to sham-operated mice, TAC mice exhibited decreased LV ejection fraction and increased hypertrophy, dilation, fibrosis, apoptosis, and oxidative stress. In contrast, TAC mice treated with NMEG-CGRP demonstrated significant improvements in cardiac function and cellular and biochemical parameters when compared to TAC mice. These findings demonstrate the therapeutic potential of NMEG-CGRP in the treatment of established cardiovascular dysfunction and its progression in pressure overload-induced HF. Full article

SH3 Domain Binding Kinase Family Member 2 (SBK2) is a critical kinase in atrial cardiomyocyte differentiation. However, its phospho-targets, its role in ventricle function, and its role in cardiac disease progression are unknown. Notably, SBK2 has been shown to be downregulated in the ventricular myocardium of several mouse models that recapitulate human desmin-related cardiomyopathies. To restore SBK2 expression, adenoviruses were constructed to promote cardiomyocyte-restricted SBK2 expression and injected at postnatal day 0. This significantly increased ejection fraction at 1 month of age relative to control hearts. However, in 3-month nontransgenic (NTG) and desmin-related cardiomyopathy hearts, the overexpression of SBK2 opposed increases in ejection fraction and left ventricular posterior wall thickness. These findings provide the first in vivo evidence that SBK2 plays a vital role in left ventricular function. To elucidate the molecular mechanism behind the physiological effects of SBK2 on the heart, we performed mass spectrometry combined with phospho-enrichment on ventricular tissue with and without SBK2 overexpression. We identified multiple phosphorylation sites on SBK2 and used AlphaFold3 to model how this phosphorylation likely affects SBK2’s role in phosphorylating the splicing factor SRSF7. We propose a novel mechanism by which SBK2 regulates splicing to promote cardiomyocyte development. Full article

Petroleum pollution can pose a serious threat to soil health and its ecological functions. This study investigated the efficacy of bacterial treatments for bioremediation of diesel-contaminated soil under outdoor conditions for a period of 4 months. Unlike most previous studies conducted under laboratory conditions, this study applied single and multi-bacterial consortia directly into diesel-contaminated soil under outdoor conditions, evaluating both hydrocarbon degradation and soil toxicity changes. Three treatments using a single strain, a 4-strain consortium, and an 8-strain consortium were applied to 2% (v/w) diesel-contaminated soil, and their performance was compared to uncontaminated and untreated controls. Total petroleum hydrocarbon (TPH) degradation was quantified using GC-FID, and the soil toxicity was assessed using Eisenia fetida toxicity test and higher plant germination assays. As the experiment demonstrated, the multi-strain bacterial consortium (BT3) achieved the highest TPH degradation (78.3%) and demonstrated significant reduction in long-chain hydrocarbon fractions (C₁₄-C₂₈). Toxicity measurements showed that all three bioremediation treatments, especially BT3, significantly increased earthworm survival, body weight change and plant germination rate after the bioremediation. Microbial community analysis based on 16S rRNA sequencing revealed significant shifts in the dominant bacterial genera over time, accompanied by a noticeable reduction in alpha diversity. In particular, BT3 showed a significant decrease in Shannon diversity index values from 9.4 at S₁ to 6.9 at S₃ (p < 0.01), whereas BT1 and BT2 remained relatively stable (p > 0.05). Overall, the results demonstrated that all three bacterial treatments significantly enhanced diesel degradation and reduced soil toxicity under outdoor conditions, highlighting their potential for future large-scale applications in sustainable soil remediation. Importantly, this study combines constructed microbial consortia with multi-level toxicity assessments, providing a comprehensive framework to guide future bioremediation strategies. Full article