Search Results (204)

This study reports the development of polyvinylidene fluoride (PVDF) membranes decorated with a copper(II) complex (CuL) for the removal of organic pollutants from wastewater. Using Drimaren Red X-6BN (DRX-6BN) as a probe, the PVDF membrane with the lowest CuL loading (PVDF/PDA/CuL-4) reached an adsorption capacity of 19.78 mg/g at 300 min, with removal of up to 50% DRX-6BN. Kinetic analysis favored Elovich (R² > 0.9928; RMSE < 0.4489) and the pseudo-second-order model (R² > 0.9540; RMSE < 1.1388), consistent with chemisorption. Intraparticle diffusion occurred in two steps. In the presence of 20 mg/L of hydrogen peroxide (H₂O₂), the removal was >80% within 180 min at higher CuL loadings (PVDF/PDA/CuL-40). In oily wastewater, PVDF/PDA/CuL-4 achieved ~100% COD removal in 120 min with H₂O₂, whereas pristine PVDF achieved 38.5%. Storage stability tests demonstrated the preservation of catalytic and separation performance for at least three months. All tests were conducted at pH ≈ 6.0 and a temperature of 25 °C. In contrast to many catalytic membranes, these membranes operate at near-neutral pH and ambient temperature in the absence of radiation. The results highlight PVDF membranes decorated with CuL as a robust and sustainable approach for the treatment of oily effluents, particularly by combining Fenton-like processes under mild conditions. Full article

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition with a complex genetic architecture. Dissecting the interplay between inherited variants and high-impact de novo variants is critical for understanding its etiology. We conducted a family-based study involving 42 families with ASD (139 individuals). Using a targeted next-generation sequencing (NGS) panel of 236 genes, we identified and characterized rare inherited and de novo variants in affected probands, parents, and unaffected siblings. Our analysis revealed a complex genetic landscape marked by diverse inheritance patterns. De novo variants were predominantly observed in individuals with atypical autism, while biparental (homozygous) inheritance was more common in Asperger syndrome. Maternally inherited variants showed significant enrichment in intronic regions, pointing to a potential regulatory role. We also detected variants in several high-confidence ASD risk genes, including SHANK3, MYT1L, MCPH1, NIPBL, and TSC2, converging on pathways central to synaptic function and neurogenesis. Across the cohort, five variants of uncertain significance (VUS) were identified, comprising two inherited variants in ABCC8 and additional variants in CUL23, TSC2, and MCPH1. Our findings underscore the profound genetic heterogeneity of ASD and suggest that distinct genetic mechanisms and inheritance patterns may contribute to different clinical presentations within the spectrum. This highlights the power of family-based genomic analyses in elucidating the complex interplay of inherited and de novo variants that underlies ASD. Full article

New energy vehicles face a critical challenge in balancing the thermal safety management of high-specific-energy battery systems with the simultaneous improvement of energy density. With the large-scale application of high-energy-density systems such as silicon-based anodes and solid-state batteries, their inherent thermal runaway risks pose severe challenges to battery thermal management systems (BTMS). Currently, the thermal insulation performance, temperature resistance, and fire protection capabilities of flame-retardant materials (e.g., foam cotton, fiber felts) used in automotive batteries are inadequate to meet the demands of intense combustion and high temperatures generated during thermal failure in high-energy-density batteries. Against this backdrop, thermal insulation and fireproof aerogel materials are emerging as a revolutionary solution for the next generation of power battery thermal protection systems. Leveraging their nanoporous structure’s exceptional thermal insulation properties (thermal conductivity of 0.013–0.018 W/(m·K) at room temperature) and extreme fire resistance (temperature resistance > 1100 °C/UL94 V-0 flame retardancy), aerogels are gaining prominence. This article provides a systematic review of thermal runaway phenomena in automotive batteries and corresponding protective measures. It highlights recent breakthroughs in the selection of material systems, optimization of preparation processes, and fiber–matrix composite technologies for automotive fireproof aerogel composites. The core engineering values of these materials, such as blocking thermal runaway propagation, reducing system weight, and improving volumetric efficiency, are quantitatively validated. Furthermore, the paper explores future research directions, including the development of low-cost aerogel composites and the design of organic–inorganic hybrid composite structures, aiming to provide a foundation and industrial pathway for the research and development of next-generation high-performance battery thermal management systems. Full article

TRIM48 is a human-specific tripartite motif (TRIM) family protein with E3 ubiquitin ligase activity that plays a significant role in the oxidative stress response and tumor suppression. However, the mechanisms regulating TRIM48 expression remain unknown. In this study, we demonstrate that TRIM48 is targeted for ubiquitination-dependent degradation by S-phase kinase-associated protein 1 (Skp1)-Cullin1 (Cul1)-F-box protein (SCF) ubiquitin ligase complex, containing F-box protein 22 (FBXO22) as a substrate recognition subunit. We found that TRIM48 is a rapid turnover protein, as evidenced by the fast and drastic decrease in its protein expression level in the presence of a protein synthesis inhibitor cycloheximide, which was suppressed by knocking down either Skp1, Cul1 or FBXO22. Exogenous FBXO22 expression promoted K48-linked polyubiquitination and degradation of TRIM48. FBXO22 deficiency accelerated oxidative stress-induced activation of apoptosis signal-regulating kinase 1 (ASK1) and cell death, which was reversed by additional TRIM48 knockdown. Collectively, our findings identify the FBXO22 SCF complex as a key negative regulator of TRIM48-driven ASK1-activation and cell death under oxidative stress. The dysregulation of this axis may underlie human-specific pathologies, such as tumorigenesis and oxidative stress-associated disorders, highlighting its potential as a target for novel therapeutic interventions. Full article

Cadmium (Cd) pollution poses a serious threat to freshwater ecosystems. The freshwater mussel Anodonta woodiana is increasingly used as a bioindicator for monitoring Cd pollution in aquatic environments. However, the primary routes of Cd accumulation in A. woodiana remain unclear, and the molecular regulatory mechanisms underlying Cd accumulation are poorly understood. To address these gaps, this study employed a novel stable isotope dual-tracer technique to trace Cd from water (waterborne ¹¹²Cd) and the green alga Chlorella vulgaris (dietary ¹¹³Cd) during the simultaneous exposure experiment. Comparative transcriptomic analysis was then conducted to characterize molecular responses in A. woodiana following Cd exposure. The results showed that although newly accumulated ¹¹²Cd and ¹¹³Cd increased with exposure concentration and duration, the relative importance of ¹¹²Cd (91.6 ± 2.8%) was significantly higher than that of ¹¹³Cd (8.4 ± 2.8%) (p < 0.05). Cd exposure induced differentially expressed genes primarily enriched in the metabolic processes, cellular processes, and/or the ubiquitin-mediated proteolysis pathway. Within the ubiquitin-mediated proteolysis pathway, TRIP12 (E3 ubiquitin-protein ligase TRIP12) and Cul5 (cullin-5) were significantly upregulated. The findings will provide critical insights for interpreting Cd biomonitoring data in freshwater environments using mussels as bioindicators. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article

A Sanskrit manuscript of the Prajñāpāramitā or Perfection of Wisdom in eight thousand verses, now in the Cambridge University Library, Add.1643, is one of the most ambitiously designed South Asian manuscripts from the eleventh century, with the highest number of painted panels known among the dated manuscripts from medieval South Asia until 1400 CE. Thanks to the unique occurrence of a caption written next to each painted panel, it is possible to identify most images in this manuscript as representing those of famous pilgrimage sites or auspicious images of specific locales. The iconographic program transforms Add.1643 into a portable device containing famous pilgrimage sites of the Buddhist world known to the makers and users of the manuscript in eleventh-century Nepal. It is one compact colorful package of a book, which can be opened and experienced in its unfolding three-dimensional space, like a virtual or imagined pilgrimage. Building on the recent research focusing on early medieval Buddhist sites across Monsoon Asia and analyzing the representational potentials and ontological values of painting, this essay demonstrates how this early eleventh-century Nepalese manuscript (Add.1643) and its visual program document and remember the knowledge of maritime travels and the transregional and intraregional activities of people and ideas moving across Monsoon Asia. Despite being made in the Kathmandu Valley with a considerable physical distance from the actual sea routes, the sites remembered in the manuscript open a possibility to connect the dots of human movement beyond the known networks and routes of “world systems”. Full article

In this study, 3-chlorothiophene-2-carboxylic acid (HL) was used as a main ligand to successfully synthesize four novel complexes: [Cu(L)₂(Py)₂(OH₂)₂] (1), [Co(L)₂(Py)₂(OH₂)₂] (2) (Py = pyridine), [{Ni(L)₂(OH₂)₄}₂{Ni(L)(OH₂)₅}]L•5H₂O (3), and [{Co(L)₂(OH₂)₄}₂{Co(L)(OH₂)₅}]L•5H₂O (4). All four compounds were identified by elemental analysis and ESI mass spectrometry, and subsequently characterized by IR spectroscopy, UV-visible diffuse reflectance spectroscopy, electron paramagnetic resonance spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography, and cyclic voltammetry. X-ray analyses revealed that complexes 1 and 2 exhibit a centrosymmetric pseudo-octahedral coordination geometry; the copper (II) and cobalt (II) metal ions, respectively, are located at the crystallographic center of inversion. The coordination sphere of the copper (II) complex is axially elongated in accordance with the Jahn–Teller effect. Intriguingly, for charge neutrality, compounds 3 and 4 crystallized as three independent mononuclear octahedrally coordinated metal centers, which are two $\left[\mathrm{M}{\mathrm{L}}_2{\left({\mathrm{O}\mathrm{H}}_2\right)}_4\right]$ complex molecules and one ${\left[\mathrm{M}\mathrm{L}{\left({\mathrm{O}\mathrm{H}}_2\right)}_5\right]}^{+}$ complex cation (M = ${\mathrm{N}\mathrm{i}}^{\mathrm{I}\mathrm{I}}$ and ${\mathrm{C}\mathrm{o}}^{\mathrm{I}\mathrm{I}}$, respectively), with the ligand anion ${\mathrm{L}}^{-}$ serving as the counter ion. The anticancer activities of these complexes were systematically assessed on human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. Among them, complex 4 shows significant inhibitory effects on leukemia K562 cells and colon cancer SW480 cells. Full article

This article stems from the PRIN GOV_REL (Urban Governance of Interreligious Dialogue) research project carried out in four Italian cities in 2023–2025 and reports on some preliminary results of the empirical enquiry held in the city of Brescia. The Brescia area is characterised by high rates of residents with an immigrant background and a consolidated presence of religious minorities (Muslim, Orthodox, Sikh, Hindu and Protestant groups), many recognised centres (mosques, temples and Christian non-Catholic churches) and a significant commitment of ethnic–religious communities to local public life. This paper examines the creation of grassroots-level interreligious dialogue, seen as a communicative process. The empirical evidence is based on material collected by participant observations and semi-structured interviews regarding four initiatives that occurred in 2024. A sociocultural analysis outlines the communicative frame: text; context; aims; acts; interlocutors and their power/freedom of expression; interactions; results. The article examines the communicative pattern of each initiative, considering an intercultural orientation and a pluralistic model of interfaith dialogue. It seeks to answer the following questions: what was the fundamental message that the promoters wanted to convey? How do the single actors communicate their perspective of religious “others”, and what results did they achieve or not achieve? The analysis leads to identifying the patterns that facilitate and/or hamper dialogue, taking into account misunderstandings and “cul-de-sac” aspects. Final recommendations highlight the recurrent breaking points that should be prevented and some premises to guarantee successful communication between members of different religions in multicultural urban spaces. Full article

Previously, we reported that mammalian cells, specifically human dermal fibroblasts (HDFs), could be transdifferentiated by lactic acid bacteria (LAB). Later, we observed that HDFs incorporated LAB-derived ribosomes, forming the ribosome-induced cell clusters (RICs) and transdifferentiating into cells derived from all three germ layers. Based on this insight, we hypothesized that incorporating ribosomes into non-mammalian cells could reveal the universality of this mechanism and open the door to commercial applications. Our current study demonstrates that ribosome incorporation can transdifferentiate chick primary muscle-derived cells (CMCs) into adipocytes, osteoblasts, and chondrocytes. Furthermore, the culture medium supernatant from ribosome-incorporated CMCs was found to significantly enhance CMC’s proliferation. RNA-seq analysis revealed that RICs-CMC exhibit increased expression of genes related to multi-lineage cell growth. In addition, we developed a novel technological shift in meat production—the “CulNet System”—which replicates organ interactions within mechanical systems for cell-cultured meat production. While significant efforts are still required to implement this technology in a cost-effective manner, we believe that combining the “CulNet System” with ribosome-incorporated multipotent cells that have prolonged culture capability could substantially improve the scalability and cost-effectiveness of cultured chicken meat production. This report highlights a promising approach for cell-culture-based meat production, offering a sustainable alternative to traditional methods. Full article

Objectives: Jasminoidin (JA) and ursodeoxycholic acid (UA) have been shown to exert synergistic effects on cerebral ischemia (CI) therapy, but the underlying mechanisms remain to be elucidated. Objective: To elucidate the synergistic mechanisms involved in the combined use of JA and UA (JU) for CI therapy using a driver-induced modular screening (DiMS) strategy. Methods: Network proximity and topology-based approaches were used to identify synergistic modules and driver genes from an anti-ischemic microarray dataset (ArrayExpress, E-TABM-662). A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in 30 Sprague Dawley rats, divided into sham, vehicle, JA (25 mg/mL), UA (7 mg/mL), and JU (JA:UA = 1:1) groups. After 90 minutes of ischemia, infarct volume and neurological deficit scores were evaluated. Western blotting was performed 24 h after administration to validate key protein changes. Results: Six, eleven, and four drug-responsive On_modules were identified for JA, UA, and JU, respectively. Three synergistic modules (Sy-modules, JU-Mod-7, 8, and 10) and 12 driver genes (e.g., NRF1, FN1, CUL3) were identified, mainly involving the PI3K-Akt and MAPK pathways and regulation of the actin cytoskeleton. JA and UA synergistically reduced infarct volume and neurological deficit score (2.5, p < 0.05) in MCAO/R rats. In vivo studies demonstrated that JU suppressed the expression of CUL3, FN1, and ITGA4, while it increased that of NRF1. Conclusions: JU acts synergistically on CI–reperfusion injury by regulating FN1, CUL3, ITGA4, and NRF1 and inducing the PI3K-Akt, MAPK, and actin cytoskeleton pathways. DiMS provides a new approach to uncover mechanisms of combination therapies. Full article

Ovarian tissue is critical for goose reproduction. This study aimed to investigate gene regulation by DNA methylation in relation to the reproductive traits of geese. We performed whole-genome bisulfite sequencing (WGBS) on ovarian tissues from Sichuan white geese (high-laying-rate group: HLRG, ♀ = 3; low-laying-rate group: LLRG, ♀ = 3) during the laying period. The results showed a higher level of hypermethylated differentially methylated regions (DMRs) in the HLRG, indicating a higher overall methylation level compared to the LLRG. In total, we identified 2831 DMRs and 733 differentially methylated genes (DMGs), including 363 genes with upregulated methylation. These DMGs were significantly enriched in pathways related to microtubule function (GO:0005874; GO:0000226), GnRH secretion, thyroid hormone signaling, ECM-receptor interaction, and PI3K–Akt signaling. Integration with RNA-seq data identified eight overlapping genes between DMGs and differentially expressed genes (DEGs), with five genes (CUL9, MEGF6, EML6, SYNE2, AK1BA) exhibiting a correlation between hypomethylation and high expression. EML6, in particular, emerged as a promising candidate, potentially regulating follicle growth and development in Sichuan white geese. Future studies should focus on further verifying the role of the EML6 gene. In conclusion, this study provides important insights into the regulatory mechanisms of DNA methylation influencing reproductive traits in geese, offering novel candidate markers for future goose breeding programs. Full article

The key flavonoid biosynthesis-related genes and their molecular features in rice have not been comprehensively and systematically characterized. In this study, we investigated the glumes of OsCSN1 mutants and OsCSN2 mutants and found the changes in the total flavonoid contents of the OsCSN2 mutants to be more pronounced than those of the OsCSN1 mutants and the changes in the anthocyanin contents of the OsCSN1 mutants to be more pronounced than those of the OsCSN2 mutants. In addition, key genes related to flavonoid synthesis, OsCHI, showed a more pronounced up-regulation trend, and the OsDFR gene, which encodes a precursor enzyme for anthocyanin synthesis, showed a clear down-regulation trend. And yeast two-hybrid experiments showed that OsCSN1 and OsCSN2 had the ability to interact with OsCUL4. In summary, OsCSN1 and OsCSN2 may regulate the metabolism of flavonoids in rice through CUL4-based E3 ligase, and the two subunits play different roles, laying a foundation for the study of the mechanism of flavonoid metabolism in monocotyledonous plants. Full article