Search Results (1,538)

A novel type of multifunctional hybrid membranes combining modified chitosan, functionalized multi-walled carbon nanotubes (MWCNTs), and rare earth element ion-imprinted polymers (REEIIPs) were designed and characterized. The synthesized materials were characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), X-ray diffraction (XRD), X-ray micro-tomography, and Fourier transform infrared spectroscopy (FTIR). The hybrid membranes were also studied in terms of their mechanical and rheological properties. The key element of the proper preparation of hybrid membranes using the casting method in an external magnetic field was to synthesize membrane components with appropriate magnetic properties. It was found that they showed tunable weak ferromagnetic properties, and the increase in modified nanotube addition caused the rise in the membrane’s saturation magnetization, which for Nd-selective hybrid membranes reached 0.44 emu/g. Also, the increase in thermooxidative stability was noted after introducing functionalized nanotubes into polymer matrices, which, in the case of Gd-selective membranes, were stable even up to 730 °C. The rise in the modified MWCNT addition and selection of appropriate REE ion-imprinted polymers improved mechanical (Rm and E values increase even twice) and rheological parameters (almost double growth of E′ and E″ values) of the tested membranes. Synthesized hybrid membranes showed a high rejection of matrix components and an increase in retention ratio with rising MWCNT-REEIIP addition, ultimately reaching 94.35%, 92.12%, and 90.11% for Nd, Pr, and Gd, respectively. The performed analysis confirmed homogeneous dispersion, phase compatibility, network integration, formation of a complex 3D microstructure, and improved operational stability of created hybrid membranes, which is significant for their future applications in Nd, Pr, and Gd recovery from coal fly ash extracts. Full article

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

This study investigates strategies for urban-scale renewable energy integration through a photovoltaic-centric approach, with a case study of a district in Barcelona. The methodology integrates spatial and morphological data using a geographic information system (GIS)-based and clustering framework to address challenges of CO₂ emissions, air pollution, and energy inefficiency. Rooftop availability and photovoltaic (PV) design constraints are analysed under current urban regulations. The spatial analysis incorporates building geometry and solar exposure, while an evolutionary optimisation algorithm in Grasshopper refines shading analysis, energy yield, and financial performance. Clustering methods (K-means and 3D proximity) group PV panels by solar irradiance uniformity and spatial coherence to enhance system efficiency. Eight PV deployment scenarios are evaluated, incorporating submodule integrated converter technology under a solar power purchase agreement model. Results show distinct trade-offs among PV scenarios. The standard fixed tilted (31.5° tilt, south-facing) scenario offers a top environmental and performance ratio (PR) = 66.81% but limited financial returns. In contrast, large- and huge-sized modules offer peak financial returns, aligning with private-sector priorities but with moderate energy efficiency. Medium- and large-size scenarios provide balanced outcomes, while a small module and its optimised rotated version scenarios maximise energy output yet suffer from high capital costs. A hybrid strategy combining standard fixed tilted with medium and large modules balances environmental and economic goals. The district’s morphology supports “solar neighbourhoods” and demonstrates how multi-scenario evaluation can guide resilient PV planning in Mediterranean cities. Full article

Methyltrimethyltridecylchromans (MTTCs), a class of oxygen-containing aromatic derivatives, have been used as indicators of paleosalinity in source rocks and crude oils. However, the reliability of these compounds as indicators in mature organic matter remains unclear, hindering a definitive assessment of their significance for oil–oil or oil–source rock correlation. In this study, a suite of mature oils and associated source rocks from the Paleogene Shahejie (E₂s) Formation in the Machang area, Dongpu Depression, Bohai Bay Basin, were analyzed. The distribution of bulk compositions and biomarkers in the oils and source rock extracts suggests a genetic relationship, indicating that the oils were derived from similar organic matter (predominantly algae and aquatic macrophytes) and depositional environments (low salinity), with comparable maturity levels (within the middle oil window). The β/γ-MTTC ratio, a proposed maturity indicator, appears unreliable in mature organic matter, as evidenced by its poor correlation with established maturity proxies (e.g., C₂₉ 24-ethylcholestanes αββ/(ααα + αββ)) in the studied samples. In contrast, MTTC-based salinity paraments (α/δ, α/γ, MTTCI, and the cross-plot of MTTCI versus Pr/Ph) consistently reflect a low-salinity depositional environment for these crude oils and source rocks, except in the ternary diagram of relative alkylation abundances. These findings suggest that MTTC-derived paleosalinity indicators may serve as effective tools for oil–oil or oil–source rock correlation within the middle oil window. This study provides evidence supporting the broader applicability of MTTC-based proxies for paleosalinity reconstruction and correlation studies, particularly in mature organic matter under geological conditions. The results also offer insights for regional petroleum exploration in saline lacustrine basins. Full article

Horizontal gene transfer (HGT), the non-Mendelian transfer of genetic material between organisms, is relatively frequent in prokaryotes, whereas its extent among eukaryotes remains unclear. Here, we raise the hypothesis of a possible cross-phylum HGT event involving 5S ribosomal DNA (rDNA). A specific type of 5S rDNA sequence from the anuran Xenopus laevis was highly similar to a 5S rDNA sequence of the genome of its flatworm parasite Protopolystoma xenopodis. A maximum likelihood analysis revealed phylogenetic incongruence between the gene tree and the species trees, as the 5S rDNA sequence from Pr. xenopodis was grouped along with the sequences from the anurans. Sequence divergence analyses of the gene region and non-transcribed spacer also agree with an HGT event from Xenopus to Pr. xenopodis. Additionally, we examined whether contamination of the Pr. xenopodis genome assembly with frog DNA could explain our findings but found no evidence to support this hypothesis. These findings highlight the possible contribution of HGT to the high diversity observed in the 5S rDNA family. Full article

Trichomonas vaginalis infection (TVI) is the most common curable sexually transmitted infection (STI). In this study, we aimed to assess the performances of different tests for TVI diagnosis in symptomatic Greek women, evaluating the TVI prevalence rate (PR) in Greece and comparing the latter with TVI-PR estimates from Europe. A laboratory-based cross-sectional analysis and a meta-analysis were conducted. Of 399 symptomatic Greek women, 17 had TVI, corresponding to a TVI-PR of 4.3%. The commercial nucleic acid amplification test (NAAT) achieved a sensitivity of 94.1%, which was 6% higher than the sensitivity of the culture method, 35% higher than that of the wet mount test, and 59% higher than that of the Giemsa stain test. The wet mount test achieved the lowest positive predictive value of 76.9%. All the tests had high specificity levels and negative predictive values. Data from 34 European TVI-PR studies in symptomatic women were pooled. The TVI-PR established in our study was similar to the TVI-PR estimates of 4.8% in Europe and 4.5% in Greece, with the second being higher than those of 2.1% in Northwestern Europe and 1.5% in Southern Europe but closer to that of 6.7% in Türkiye. In Greece, a European country with a relatively high TVI-PR among symptomatic women, the highly sensitive and specific, automated, point-of-care NAAT would facilitate rapid, accurate TVI diagnosis and the treatment of this target population to meet the WHO’s goal of ending STI epidemics by 2030. Full article

Orobanche cumana Wallr. is a root parasitic plant that causes considerable yield losses of up to 50% in sunflower Helianthus annuus plantations. The holoparasite fulfills its entire demand for water, minerals, and organic nutrients from the host’s vascular system. Agronomic practices alone are not effective in controlling this pest. This study investigated the mechanism of a verified plant growth-promoting strain, Streptomyces rochei D74, on the inhibition of the parasitism of O. cumana in a co-culture experiment. We conducted potted and sterile co-culture experiments using sunflower, O. cumana, and S. rochei D74. Our results suggest that the inoculated bacteria invoked the sunflower systemic resistance (SAR and ISR) by increasing the activity of resistance-related enzymes (SOD, POD, PPO, and PAL), the gene expression of systemic resistance marker genes (PR-1 and NPR1), ethylene synthesis genes (HACS. 1 and ACCO1), and JA synthesis genes (pin2 and lox). The expression levels of ISR marker genes (lox, HACS. 1, ACCO1, and pin2) increased by 1.66–7.91-fold in the seedling stage. Simultaneously, S. rochei D74 formed a protective layer on the sunflower root surface, preventing O. cumana from connecting to the vascular system of the sunflower roots. In addition, S. rochei D74 reduced 5DS synthesis of the strigol precursor substance, resulting in a reduction in O. cumana germination. These results demonstrated that the S. rochei D74 strain improved systemic resistance and decreased seed germination to prevent O. cumana parasitism. Full article

Rare earth elements (REEs) have garnered significant global attention due to their essential role in advanced technologies. Sri Lanka is endowed with various REE-bearing minerals, including the apatite-rich deposit in the Eppawala area, commonly known as Eppawala rock phosphate (ERP). However, direct extraction of REEs from ERP is technically challenging and economically unfeasible. This study introduces a novel, integrated approach for recovering REEs from ERP as a by-product of nitrophosphate fertilizer production. The process involves nitric acid-based acidolysis of apatite, optimized at 10 M nitric acid for 2 h at 70 °C with a pulp density of 2.4 mL/g. During cooling crystallization, 42 wt% of calcium was removed as Ca(NO₃)₂.4H₂O while REEs remained in the solution. REEs were then selectively precipitated as REE phosphates via pH-controlled addition of ammonium hydroxide, minimizing the co-precipitation with calcium. Further separation was achieved through selective dissolution in a sulfuric–phosphoric acid mixture, followed by precipitation as sodium rare earth double sulfates. The process achieved over 90% total REE recovery with extraction efficiencies in the order of Pr > Nd > Ce > Gd > Sm > Y > Dy. Samples were characterized for their phase composition, elemental content, and morphology. The fertilizer results confirmed the successful production of a nutrient-rich nitrophosphate (NP) with 18.2% nitrogen and 13.9% phosphorus (as P₂O₅) with a low moisture content (0.6%) and minimal free acid (0.1%), indicating strong agronomic value and storage stability. This study represents one of the pioneering efforts to valorize Sri Lanka’s apatite through a novel, dual-purpose, and circular approach, recovering REEs while simultaneously producing high-quality fertilizer. Full article

Background and Objectives: The accuracy of breast cancer diagnosis depends on the concordance between imaging features and pathological findings. While BI-RADS (Breast Imaging Reporting and Data System) provides standardized risk stratification, its correlation with histologic grade and immunohistochemical markers remains underexplored. This study assessed the diagnostic performance of BI-RADS 3, 4, and 5 classifications and their association with tumor grade and markers such as ER, PR, HER2, and Ki-67. Materials and Methods: In this prospective study, 67 women aged 33–82 years (mean 56.4) underwent both mammography and ultrasound. All lesions were biopsied using ultrasound-guided 14G core needles. Imaging characteristics (e.g., margins, echogenicity, calcifications), histopathological subtype, and immunohistochemical data were collected. Statistical methods included logistic regression, Chi-square tests, and Spearman’s correlation to assess associations between BI-RADS, histology, and immunohistochemical markers. Results: BI-RADS 5 lesions showed a 91% malignancy rate. Evaluated features included spiculated margins, pleomorphic microcalcifications, and hypoechoic masses with posterior shadowing, and were correlated with histological and immunohistochemical results. Invasive tumors typically appeared as irregular, hypoechoic masses with posterior shadowing, while mucinous carcinomas mimicked benign features. Higher BI-RADS scores correlated significantly with increased Ki-67 index (ρ = 0.76, p < 0.001). Logistic regression yielded an AUC of 0.877, with 93.8% sensitivity and 80.0% specificity. Conclusions: BI-RADS scoring effectively predicts malignancy and correlates with tumor proliferative markers. Integrating imaging, histopathology, and molecular profiling enhances diagnostic precision and supports risk-adapted clinical management in breast oncology. Full article

Clubroot is a destructive soilborne disease caused by Plasmodiophora brassicae that threatens the production of Chinese cabbage. The molecular mechanisms underlying the resistance of Chinese cabbage to clubroot remains unclear, making the identification and analysis of resistance genes crucial for developing resistant varieties. Comparative transcriptome analysis of roots from the resistant line “JJ S5-1” and the susceptible line “SYY10-1” revealed significant differences in gene expression profiles at various stages after inoculation. Weighted gene coexpression network analysis revealed midnight blue and green modules as substantially associated with disease response, with each showing positive regulatory patterns. Several defense-related genes and transcription factors important for resistance to Plasmodiophora brassicae were identified, including disease resistance proteins, PR1, PBS1, and TGA, and WRKY transcription factors, most of which were upregulated following inoculation. Key genes associated with trait-related expression patterns were analyzed and a working model was proposed to explain the mechanism of clubroot disease resistance to Plasmodiophora brassicae infection in Chinese cabbage. These findings offer a valuable resource for further investigation of the immune response in the resistance of “JJ S5-1” to clubroot disease. Full article

Research on the supply–demand relationships of ecosystem services (ESs) in alpine pastoral regions remains relatively scarce, yet it is crucial for regional ecological management and sustainable development. This study focuses on the Sanjiangyuan Region, a typical alpine pastoral area and significant ecological barrier, to quantitatively assess the supply–demand dynamics of key ESs and their spatial heterogeneity from 2000 to 2020. It further aims to elucidate the underlying driving mechanisms, thereby providing a scientific basis for optimizing regional ecological management. Four key ES indicators were selected: water yield (WY), grass yield (GY), soil conservation (SC), and habitat quality (HQ). ES supply and demand were quantified using an integrated approach incorporating the InVEST model, the Revised Universal Soil Loss Equation (RUSLE), and spatial analysis techniques. Building on this, the spatial patterns and temporal evolution characteristics of ES supply–demand relationships were analyzed. Subsequently, the Geographic Detector Model (GDM) and Geographically and Temporally Weighted Regression (GTWR) model were employed to identify key drivers influencing changes in the comprehensive ES supply–demand ratio. The results revealed the following: (1) Spatial Patterns: Overall ES supply capacity exhibited a spatial differentiation characterized by “higher values in the southeast and lower values in the northwest.” Areas of high ES demand were primarily concentrated in the densely populated eastern region. WY, SC, and HQ generally exhibited a surplus state, whereas GY showed supply falling short of demand in the densely populated eastern areas. (2) Temporal Dynamics: Between 2000 and 2020, the supply–demand ratios of WY and SC displayed a fluctuating downward trend. The HQ ratio remained relatively stable, while the GY ratio showed a significant and continuous upward trend, indicating positive outcomes from regional grass–livestock balance policies. (3) Driving Mechanisms: Climate and natural factors were the dominant drivers of changes in the ES supply–demand ratio. Analysis using the Geographical Detector’s q-statistic identified fractional vegetation cover (FVC, q = 0.72), annual precipitation (PR, q = 0.63), and human disturbance intensity (HD, q = 0.38) as the top three most influential factors. This study systematically reveals the spatial heterogeneity characteristics, dynamic evolution patterns, and core driving mechanisms of ES supply and demand in an alpine pastoral region, addressing a significant research gap. The findings not only provide a reference for ES supply–demand assessment in similar regions regarding indicator selection and methodology but also offer direct scientific support for precisely identifying priority areas for ecological conservation and restoration, optimizing grass–livestock balance management, and enhancing ecosystem sustainability within the Sanjiangyuan Region. Full article

Background: Breast cancer is the most prevalent women’s cancer, representing about a third of all cancers diagnosed in women. Estrogen receptor (ER) is an important transcription factor expressed in 70% to 75% of all breast cancers. Of these breast cancers, the majority express ER robustly in 91–100% of tumor cells. However, a minority of breast cancers express ER in intermediate levels between 11% and 90% of tumor cells. The characteristics and outcomes of this intermediate subset of ER-positive breast cancers are not well studied. Methods: We retrospectively reviewed the medical records of all breast cancer patients treated in our Cancer Center over a period of 8 years. Patients were grouped according to the level of ER expression in tumors with negative/low ER expression, intermediate ER expression, and high ER expression, and the groups were compared for tumor characteristics and outcomes. Results: Patients with high ER levels (91% to 100%) represented 75.6% (600 of 794 patients), patients with intermediate ER expression represented 11.5% of the entire group (91 of 794 patients), and patients with negative/low ER expression (ER expression 0–10%) represented 12.9% of the entire cohort (103 of 794 patients). Patients with intermediate ER expression presented at a younger age than patients with high-ER cancers, as well as a more advanced stage and higher grade. These characteristics were more akin to patients with negative/low ER levels. Mastectomy was the surgical method of resection more commonly in ER-intermediate tumors than in ER-high tumors. The relapse-free survival (RFS) of patients with ER-intermediate cancers was worse than the RFS of patients that expressed ER robustly. Conclusion: The level of expression of ER defines groups of patients with varying characteristics and prognoses. Patients in the intermediate ER expression group had notable differences from patients in the high ER expression group including younger age, (more often) a higher grade, and low PR positivity. Differences observed between the group of patients with intermediate ER expression and that with high ER expression may help to prioritize therapeutic algorithms. Full article

The coronavirus disease 2019 (COVID-19) pandemic has led to substantial health and financial burdens worldwide, and vaccines provide hope for reducing the burden of this pandemic. However, vaccinated people remain at risk for SARS-CoV-2 infection. Genome-wide association studies (GWASs) may identify potential genetic factors involved in the development of COVID-19 breakthrough infections (BIs); however, very few or no GWASs have been conducted for COVID-19 BI thus far. We conducted a GWAS and detailed bioinformatics analysis on COVID-19 BIs in a European population via the UK Biobank (UKBB). We conducted a series of analyses at different levels, including SNP-based, gene-based, pathway, and transcriptome-wide association analyses, to investigate genetic factors associated with COVID-19 BIs and hospitalized infections. The polygenic risk score (PRS) and Hoeffding’s test were performed to reveal the genetic relationships between BIs and other medical conditions. Two independent loci (LD-clumped at r² = 0.01) reached genome-wide significance (p < 5 × 10⁻⁸), including rs36170929, which mapped to LOC102725191/VWDE, and rs28645263, which mapped to RETREG1. A pathway enrichment analysis highlighted pathways such as viral myocarditis, Rho-selective guanine exchange factor AKAP13 signaling, and lipid metabolism. The PRS analyses revealed significant genetic overlap between COVID-19 BIs and heart failure and between HbA1c and type 1 diabetes. Genetic dependence was also observed between COVID-19 BIs and asthma, lung abnormalities, schizophrenia, and type 1 diabetes on the basis of Hoeffding’s test. This GWAS revealed two significant loci that may be associated with COVID-19 BIs and a number of genes and pathways that may be involved in BIs. Genetic overlap with other diseases was identified. Further studies are warranted to replicate these findings and elucidate the mechanisms involved. Full article

The use of CH₄ and CO₂ as fuels in direct internal reforming solid oxide fuel cells (DIR-SOFCs) is a promising strategy for efficient power generation with reduced greenhouse gas emissions. In this study, Ni catalysts supported on Ce–Pr mixed oxides with varying Pr contents (0–80 mol%) were synthesized, calcined at 1200 °C, and tested for dry reforming of methane (DRM), aiming at their application as catalytic layers in SOFC anodes. Physicochemical characterization (XRD, TPR, TEM) showed that increasing Pr loading enhances catalyst reducibility and promotes the formation of the Pr₂NiO₄ phase, which contributes to the generation of smaller Ni⁰ particles after reduction. Catalytic tests revealed that all samples exhibited low-carbon deposition, attributed to the large Ni crystallites. The catalyst with 80 mol% Pr showed the best performance, achieving the highest CH₄ conversion (72%), a H₂/CO molar ratio of 0.89, and improved stability. These findings suggest that Ni/Ce_0.2Pr_0.8 could be a promising candidate for use as a catalyst layer of anodes in DIR-SOFC anodes. Although electrochemical data are not yet available, future work will evaluate the catalyst’s performance and durability under SOFC-relevant conditions. Full article

Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7^® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Full article