Search Results (21)

Objective: Rare-earth elements are extensively employed across diverse industrial sectors, increasingly raising concerns about their potential health hazards in both occupational and environmental contexts. Samarium oxide (Sm₂O₃), a routinely processed rare-earth product, reproducibly precipitates pulmonary fibrosis in experimental models, yet the molecular circuitry that transduces its fibrogenic signal remains almost entirely unmapped. This study aims to elucidate the role of miR-214-3p in Sm₂O₃-induced pulmonary fibrosis and to investigate its regulatory mechanism at the molecular level. Methods: A murine model of pulmonary fibrosis was established via intratracheal instillation of Sm₂O₃, and histopathological changes were assessed using hematoxylin and eosin (H&E) and Masson’s trichrome staining. RNA sequencing was performed on lung tissues to identify differentially expressed mRNAs. Leveraging our previously generated miRNA landscape of Sm₂O₃-exposed lungs, we subjected the dataset to Gene Ontology and KEGG enrichment analyses, which convergently identified miR-214-3p as the top-ranking candidate regulator of the fibrogenic MAPK axis. The direct targeting of MAP2K3 by miR-214-3p was validated using a dual-luciferase reporter assay. Expression levels of fibrotic markers (α-SMA, Collagen I) and key components of the MAPK signaling pathway (MAP2K3, p-MAPK14, MST1) were quantified in both in vivo and in vitro models using qRT-PCR and Western blotting. Gain- and loss-of-function studies, complemented by rescue assays, were performed in human embryonic lung fibroblasts (HELFs) via transient transfection of miR-214-3p mimics, inhibitors, or MAP2K3-overexpression plasmids. Cell proliferation was evaluated using the EdU assay, and TGF-β1 secretion was measured by ELISA. Results: Sm₂O₃ exposure induced significant pulmonary fibrosis in mice, accompanied by marked downregulation of miR-214-3p and upregulation of MAP2K3 in lung tissues. Overexpression of miR-214-3p or silencing of MAP2K3 effectively suppressed Sm₂O₃-induced fibroblast activation, including reduced cell proliferation, decreased expression of α-SMA and Collagen I, and inhibition of p38 MAPK phosphorylation. Notably, ectopic overexpression of MAP2K3 reversed the protective effects conferred by miR-214-3p, confirming a functional rescue. Conclusions: miR-214-3p directly silences MAP2K3, thereby blunting p38 MAPK-driven fibrogenesis after Sm₂O₃ exposure. Our data unveil a miR-214-3p–MAP2K3–p38 MAPK axis that constitutes a readily druggable target for rare-earth-element-induced pulmonary fibrosis. Full article

Background: Bacterial infections are a major challenge in food processing and public health, and there is an urgent need to develop novel antimicrobial agents. Objectives: The purpose of this study is to investigate the potential mechanism and key components of Pinctada martensii antimicrobial proteins (Pm-Aps) to provide a theoretical basis for the development of novel antimicrobial agents. Methods: The researchers used Vibrio parahaemolyticus (VP) to stimulate Pinctada martensii, extracted the antimicrobial proteins, and analyzed their antimicrobial activities, potential mechanisms of action, and key components using proteomics. Results: The results showed that the antimicrobial activity of Pm-Aps, with broad-spectrum antimicrobial effects, was significantly enhanced after VP stimulation. This was associated with the upregulation of LAAO, CHDH, TLR2, ATG16L1, BAK, CLCA4, and CASP8 and the downregulation of MCM3, MCM5, DTYMK, PLK1, FBXO6, LPCAT3, GST, LAMTOR5, CYP17A, CTSA, and RRM1. It is hypothesized that these proteins may inhibit bacterial growth and multiplication by activating immune-related signaling pathways, inhibiting DNA replication and repair, and inducing apoptosis and autophagy. Furthermore, it was found that LAAO may be a key component of the antimicrobial action of Pm-Aps, killing bacteria by catalyzing the oxidation of amino acids to produce hydrogen peroxide (H₂O₂). Conclusions: These results strongly suggest that Pm-Aps is an effective antimicrobial protein, and it is expected that new LAAO can be obtained from Pm-Aps. Full article

A crop pretreatment with silicon was combined with passive modified atmosphere packaging (PMAP) in a thermoformed recycled PET packaging format as a novel approach to minimize the quality degradation in mushrooms. This study was aimed to evaluate the effects of (a) two preharvest treatments, namely preharvest control (PHTC) and preharvest silicon treatment (PHTS) and (b) four packaging lid formats, namely PMAP1: a single hole of 1.1 mm size, PMAP2: two holes of 0.53 mm size, PMAP3: three holes of 0.53 mm size, and PMAPC: OMNI-PW micro perforated cling film as a control on the quality and shelf life of mushrooms during five days of storage at 4 °C and 99.9% RH. The results of the analysis of variance showed that packaging type, storage days, and the double interaction effects of storage days × packaging type had significant effects (p < 0.0001) on the changes in O₂, CO₂, colour L* and a* values, ΔE, total soluble solids (TSS), and the density of mushrooms. Density, electrolyte leakage (EL), and TSS were significantly affected by the double interaction effects of preharvest treatment × packaging type. Overall, PMAP1, PMAP2, and PMAP3 resulted in lower O₂ + higher CO₂ within packages compared with the conventional control. A preharvest silicon treatment had little overall effect. PMAP 1, 2 and 3 had a significantly lower ΔE (=better quality) after 5 days storage compared to PMAPC which had the highest ΔE (lowest quality) overall. PMAP1 and PMAP2 had the lowest EL values compared to PMAP3 and PMAPC. PMAP1, PMAP2, and PMAP3 all gave better TSS levels and density compared to PMAPC. Notably, this study proved that a perforation-mediated MAP design for mushrooms packaged in a thermoformed recycled PET packaging format maintained improved CO₂, lowered O₂, and reduced EL while maintaining TSS and the density of the mushrooms during the storage period. Full article

Under caged stress conditions, severe disruptions in duck intestinal barrier function, which adversely affect economic performance, have been observed. MiRNAs play a crucial role in cellular processes, but the mechanisms underlying their involvement in repairing oxidative stress-induced damage to duck intestinal barriers have not been elucidated. We performed miRNA-seq and protein tandem mass tagging (TMT) sequencing and identified differentially expressed miRNAs and proteins in oxidative stress-treated ducks. Dual-luciferase reporter vector experiments, RT-qPCR, and Western blotting revealed the regulatory role of apla-miR-106a-5p/MAP3K2 in intestinal barrier damage repair. The results showed that oxidative stress led to shortened villi and deepened crypts, impairing intestinal immune function. Significant downregulation of apla-miR-106a-5p was revealed by miRNA-seq, and the inhibition of its expression not only enhanced cell viability but also improved intestinal barrier function. TMT protein sequencing revealed MAP3K2 upregulation in caged-stressed duck intestines, and software analysis confirmed MAP3K2 as the target gene of apla-miR-106a-5p. Dual-fluorescence reporter gene experiments demonstrated direct targeting of MAP3K2 by apla-miR-106a-5p. RT-qPCR showed no effect on MAP3K2 expression, while Western blot analysis indicated that MAP3K2 protein expression was suppressed. In summary, apla-miR-106a-5p targets MAP3K2, regulating gene expression at the transcriptional level and facilitating effective repair of intestinal barrier damage. This discovery provides new insights into the molecular mechanisms of physiological damage in ducks under caged stress, offering valuable guidance for related research. Full article

Planning for resilient cities requires an evidence-based understanding of flood risk and the involvement of stakeholders and local actors. The paper addresses research developed within the URCA!—Urban Resilience to Climate Change: to activate the participatory mapping and decision support tool for enhancing sustainable urban drainage—project. A top-down/bottom-up participatory and flexible methodology for the conception of participatory mapping aimed at the planning and installation of sustainable urban drainage systems (SUDS) on the territory is then developed. The innovative methodology is applied and tested in the case study of the Sampierdarena district in Genoa, northern Italy. This research paper illustrates the development of a participatory map (Pmap) that can support the implementation of SUDS as mitigation/adaptation strategies, integrating technical assessment and containing community visions and expectations. Findings concerning the connections between proposed SUDS locations and their frequencies confirm the relevance of the commercial area and the main traffic lanes along, confirming that all zones characterized by intense vehicular and pedestrian flow are suitable for SUDS as a solution to contribute to urban flood resilience. The georeferenced and intergenerational Pmap may be integrated into a decision support system to be developed as a guidance tool for the public administration. Full article

Steroids are often considered valuable molecular tools for the development of anticancer agents with improved pharmacological properties. Conjugation of metal chelating moieties with a lipophilic sterane backbone is a viable option to obtain novel anticancer compounds. In this work, two estradiol-based hybrid molecules (PMA-E2 and DMA-E2) with an (N,N,O) binding motif and their Cu(II) complexes were developed. The lipophilicity, solubility, and acid-base properties of the novel ligands were determined by the combined use of UV-visible spectrophotometry, pH-potentiometry, and ¹H NMR spectroscopy. The solution speciation and redox activity of the Cu(II) complexes were also investigated by means of UV-visible and electron paramagnetic resonance spectroscopy. Two structurally analogous ligands (PMAP and DMAP) were also included in the studies for better interpretation of the solution chemical data obtained. Three pK_a values were determined for all ligands, revealing the order of the deprotonation steps: pyridinium-NH⁺ or NH(CH₃)₂⁺, secondary NH₂⁺, and OH. The dimethylamine derivatives (DMA-E2, DMAP) are found in their H₂L⁺ forms in solution at pH 7.4, whereas the fraction of the neutral HL species is significant (34–37%) in the case of the pyridine nitrogen-containing derivatives (PMA-E2, PMAP). Both estradiol derivatives were moderately cytotoxic in human breast (MCF-7) and colon adenocarcinoma (Colo-205) cells (IC₅₀ = 30–63 μM). They form highly stable complexes with Cu(II) ions capable of oxidizing ascorbate and glutathione. These Cu(II) complexes are somewhat more cytotoxic (IC₅₀ = 15–45 μM) than their corresponding ligands and show a better selectivity profile. Full article

The binding of Host Defense Peptides (HDPs) to the endotoxin of Gram-negative bacteria has important unsolved aspects. For most HDPs, it is unclear if binding is part of the antibacterial mechanism or whether LPS actually provides a protective layer against HDP killing. In addition, HDP binding to LPS can block the subsequent TLR4-mediated activation of the immune system. This dual activity is important, considering that HDPs are thought of as an alternative to conventional antibiotics, which do not provide this dual activity. In this study, we systematically determine, for the first time, the influence of the O-antigen and Lipid A composition on both the antibacterial and anti-endotoxin activity of four HDPs (CATH-2, PR-39, PMAP-23, and PMAP36). The presence of the O-antigen did not affect the antibacterial activity of any of the tested HDPs. Similarly, modification of the lipid A phosphate (MCR-1 phenotype) also did not affect the activity of the HDPs. Furthermore, assessment of inner and outer membrane damage revealed that CATH-2 and PMAP-36 are profoundly membrane-active and disrupt the inner and outer membrane of Escherichia coli simultaneously, suggesting that crossing the outer membrane is the rate-limiting step in the bactericidal activity of these HDPs but is independent of the presence of an O-antigen. In contrast to killing, larger differences were observed for the anti-endotoxin properties of HDPs. CATH-2 and PMAP-36 were much stronger at suppressing LPS-induced activation of macrophages compared to PR-39 and PMAP-23. In addition, the presence of only one phosphate group in the lipid A moiety reduced the immunomodulating activity of these HDPs. Overall, the data strongly suggest that LPS composition has little effect on bacterial killing but that Lipid A modification can affect the immunomodulatory role of HDPs. This dual activity should be considered when HDPs are considered for application purposes in the treatment of infectious diseases. Full article

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results. Full article

In this study, poly(m-aminophenol) (PmAP) has been investigated as a multi-functional conductive supercapacitor binder to replace the conventional non-conductive binder, namely, poly(vinylene difluoride) (PVDF). The kye benefits of using PmAP are that it is easily soluble in common organic solvent and has good film-forming properties, and also its chemical functionalities can be involved in pseudocapacitive reactions to boost the capacitance performance of the electrode. A new ternary nanocomposite film based on vanadium pentoxide (V₂O₅), amino-functionalized graphene (amino-FG) and PmAP was fabricated via hydrothermal growth of V₂O₅ nanoparticles on graphene surfaces and then blending with PmAP/DMSO and solution casting. The electrochemical performances of V₂O₅/amino-FG/PmAP nanocomposite were evaluated in two different electrolytes, such as KCl and Li₂SO₄, and compared with those of V₂O₅/amino-FG nanocomposite with PVDF binder. The cyclic voltametric (CV) results of the V₂O₅/amino-FG/PmAP nanocomposite exhibited strong pseudocapacitive responses from the V₂O₅ and PmAP phases, while the faradaic redox reactions on the V₂O₅/amino-FG/PVDF electrode were suppressed by the inferior conductivity of the PVDF. The V₂O₅/amino-FG/PmAP electrode delivered a 5-fold greater specific capacitance than the V₂O₅/amino-FG/PVDF electrode. Solid-state asymmetric supercapacitors (ASCs) were assembled with V₂O₅/amino-FG/PmAP film as a positive electrode, and their electrochemical properties were examined in both KCl and Li₂SO₄ electrolytes. Although the KCl electrolyte-based ASC has greater specific capacitance, the Li₂SO₄ electrolyte-based ASC delivers a higher energy density of 51.6 Wh/kg and superior cycling stability. Full article

Introduction: The standard of care for people with locally advanced lung cancer (LALC) who cannot be operated on is (chemo)-radiation. Despite the application of dose constraints, acute pulmonary toxicity (APT) still often occurs. Prediction of APT is of paramount importance for the development of innovative therapeutic combinations. The two models were previously individually created. With success, the Rad-model incorporated six radiomics functions. After additional validation in prospective cohorts, a Pmap-model was created by identifying a specific region of the right posterior lung and incorporating several clinical and dosimetric parameters. To create and test a novel model to forecast the risk of APT in two cohorts receiving volumetric arctherapy radiotherapy (VMAT), we aimed to include all the variables in this study. Methods: In the training cohort, we retrospectively included all patients treated by VMAT for LALC at one institution between 2015 and 2018. APT was assessed according to the CTCAE v4.0 scale. Usual clinical and dosimetric features, as well as the mean dose to the pre-defined Pmap zone (DMean_Pmap), were processed using a neural network approach and subsequently validated on an observational prospective cohort. The model was evaluated using the area under the curve (AUC) and balanced accuracy (Bacc). Results: 165 and 42 patients were enrolled in the training and test cohorts, with APT rates of 22.4 and 19.1%, respectively. The AUCs for the Rad and Pmap models in the validation cohort were 0.83 and 0.81, respectively, whereas the AUC for the combined model (Comb-model) was 0.90. The Bacc for the Rad, Pmap, and Comb models in the validation cohort were respectively 78.7, 82.4, and 89.7%. Conclusion: The accuracy of prediction models were increased by combining radiomics, DMean_Pmap, and common clinical and dosimetric features. The use of this model may improve the evaluation of APT risk and provide access to novel therapeutic alternatives, such as dose escalation or creative therapy combinations. Full article

Pinus massoniana Lamb. is found in 17 Chinese provinces and is an important timber tree species in southern China. The current seasonal drought climate is becoming increasingly severe, threatening P. massoniana growth and limiting the development of the P. massoniana industry. Plant growth, development, and stress were all regulated by AP2/ERF. We identified 124 AP2/ERF transcription factor family members in this study and discovered that all the genes had their own conserved structural domains and that PmAP2/ERFs were divided into 12 subfamilies with high conservation and similarity in gene structure and evolutionary level. Nine PmAP2/ERF genes were constitutively expressed under drought treatment, and it was hypothesized that the PmAP2/ERF96 gene negatively regulated drought stress, PmAP2/ERF46 and PmAP2/ERF49 genes showed a positive or negative response to drought in different tissues, while the remaining six genes were positively regulated. The PmAP2/ERF genes responded to drought stress following treatment with the exogenous hormones SA, ABA, and MeJA, but the expression patterns differed, with each gene responding to at least one exogenous hormone to induce up-regulation of expression under drought stress, with PmAP2/ERF11, PmAP2/ERF44, PmAP2/ERF77, and PmAP2/ERF80 genes significantly induced by three hormones. The genes mentioned above may be involved in hormone signaling pathways in response to drought stress. The results indicate that the PmAP2/ERF genes may positively or negatively regulate the corresponding signaling pathways in P. massoniana to improve drought resistance. Full article

Fig is a very perishable fruit with short postharvest life. Low-cost postharvest techniques should be employed to reduce fresh fig postharvest losses. The purpose of this study was to design a passive modified atmosphere packaging (PMAP) to extend the shelf-life of fresh ‘Dottato’ figs stored at 4 °C for 21 days. Physico-chemical traits and enzymatic and non-enzymatic antioxidant systems were evaluated. Storage in PMAP reduced the losses of fruit weight as well as maintained physico-chemical traits and nutraceutical traits such as polyphenol and flavonoid contents and the antioxidant activity in fresh figs. PMAP reduced oxidative stress, inducing the activities of antioxidant enzymes such as ascorbate peroxidase and catalase, involved in reactive oxygen species scavenging. A reduction in browning process due to polyphenol oxidase and guaiacol peroxidase activities was observed in PMAP samples. Multivariate analysis indicated that storage conditions and storage time affected the responses of qualitative and enzymatic traits. Fig fruit storage in PMAP was suitable to delay its postharvest decay and to preserve nutraceutical traits and antioxidative enzymes during 21 days of cold storage. Full article

Introduction: In patients treated with radiotherapy for locally advanced lung cancer, respect for dose constraints to organs at risk (OAR) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on the treatment’s completion and the patient’s quality of life. Dosimetric planning does not take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMeanPmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMeanPmap of ≥30.3 Gy or a predicted APT probability (ProbAPT) of ≥8% were associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMeanPmap via a volumetric arctherapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. Methods: Among the 207 patients included in the initial study, only patients who presented with APT of ≥grade 2 and with a probability of APT ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMeanPmap < 30.3 Gy) added to the usual constraints. The initial and optimized treatment plans were compared using the t-test for the independent variables and the non-parametric Mann–Whitney U test otherwise, regarding both doses to the OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. The risk of APT was recalculated using the new dosimetric features and the APT prediction model. Results: Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). The optimization significantly decreased the median DMeanPmap from 28.8 Gy (CI95% 24.2–33.4) to 22.1 Gy (CI95% 18.3–26.0). When recomputing the risk of APT using the new dosimetric features, the optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. Conclusion: Our approach appears to be both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of new treatment strategies, such as dose escalation or innovative treatment associations. Full article

This study evaluated the application of cold shock combined with perforation-mediated passive modified atmosphere packaging technology (CS-PMAP) for cucumber preservation through physicochemical, sensory, and nutritional qualities. The effectiveness of CS-PMAP in maintaining the quality of fresh cucumbers was studied; cucumbers were pretreated with cold shock and then packed into perforated polyethylene bags (bag size of 20 × 30 cm; film thickness of 0.07 mm; and two holes in each bag with a diameter of 6 mm), while the cucumbers without cold shock were considered as the control. Storage of the samples was performed at (13 ± 2) °C for 20 days to determine the quality changes in terms of gas composition, weight loss, skin color, texture, total soluble solids (TSS), ascorbic acid, malondialdehyde (MDA), and volatile organic compounds (VOCs). The CS-PMAP showed a significant improvement in maintaining firmness, TSS, ascorbic acid, and flavor profile of cucumbers; the control samples without cold shock showed higher weight loss and MDA levels. Results of this study confirmed that CS-PMAP has potential use in the storage of cucumbers. Full article

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood–brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1β and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway. Full article