Biological and Computational Study of the Dual Antimicrobial and Anticancer Potential of 3,4‐Dihydropyrimidin‐2(1 H )‐ones and Thiones

Abstract Sixteen 3,4‐dihydropyrimidin‐2(1 H )‐ones and ‐thiones were synthesized and evaluated for antimicrobial activity against both resistant and nonresistant bacterial strains, as well as four fungal species. Antibacterial testing revealed MIC/MBC values ranging from 0.25 to 8.0 mg/mL, with compound 20 demonstrating the most potent activity (MIC: 0.42–2.0 mg/mL). Notably, compound 16 exhibited consistent efficacy against both resistant and nonresistant strains. Antifungal activity was assessed against Aspergillus fumigatus , Aspergillus niger , Penicillium funiculosum , and Candida albicans , with compound 20 again emerging as the most effective (MIC: 0.75–2.0 mg/mL). Compounds 16 and 25 also showed antibiofilm activity, with compound 16 inhibiting biofilm formation by 70.22%. Preliminary cytotoxicity screening against cancer cell lines indicated that several compounds exhibited moderate anticancer activity. ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis suggested favorable pharmacokinetic profiles, with no violations of Lipinski's Rule of Five. Molecular docking studies suggest that the antibacterial mechanism may involve inhibition of the MurB enzyme, while antifungal activity is likely mediated through inhibition of cytochrome P450 (CYP) enzymes.These findings underscore the potential of 3,4‐dihydropyrimidin‐2(1 H )‐(thi)ones as promising lead compounds for the development of novel antibacterial and antifungal agents.

Selective In Situ Phase Segregation Enabling Efficient and Stable Protonic Ceramic Fuel Cell Cathode Performance

Abstract Efficient and reliable protonic ceramic fuel cells (PCFCs) necessitate the development of active and durable cathode materials to accelerate the sluggish oxygen reduction reaction (ORR). The most promising PCFC cathode candidates are perovskite‐type structured oxides with mixed oxygen ion, proton, and hole conductivity. However, mixed conductivity often requires materials with alkaline earth elements and the inclusion of these elements in the cathode structure leads to severe degradation in the presence of even small trace amounts of CO 2 in air. Herein, a new approach is presented to address this challenge by inducing selective in situ phase segregation to engineer the cathode surface and bulk separately. This selective phase segregation is achieved via targeted control of the size mismatch of cations in the perovskite‐type structure, enhancing charge transfer in the bulk while improving CO 2 resistance at the surface. By co‐incorporating smaller Li + and larger K + into the model BaCo 0.4 Fe 0.4 Zr 0.1 Y 0.1 O 3−δ cathode material, it is shown that Li + segregates to the surface, protecting it from CO 2 poisoning, while K + remains in the bulk and accelerates proton transport. Consequently, this in situ restructured cathode can boost the PCFC power output by 30% and improve its CO 2 tolerance fivefold in the presence of CO 2 at 600 °C.

Enhancing Multi‐Enzyme Cascade Activity in Metal‐Organic Frameworks via Controlled Enzyme Encapsulation

Abstract To position multi‐enzymes in a core‐shell structure, the conventional layer‐by‐layer approach is often used. However, this method is time‐consuming and complex, requiring multiple steps and the isolation of intermediates at each stage. To address this challenge, a sequential strategy is introduced for the controlled encapsulation of multi‐enzymes within metal‐organic frameworks (MOFs), achieving a core‐shell structure without the need for intermediate isolation. Synchrotron Terahertz‐Far‐Infrared (THz‐Far‐IR) spectroscopy is employed to monitor this encapsulation process. The results revealed that the first enzyme is co‐precipitated within the MOFs, followed by biomineralization upon the addition of a second enzyme, achieving distinct enzyme positioning. This approach is applicable to both two‐enzyme and three‐enzyme cascade systems. The results demonstrate that multi‐enzyme cascade activity is significantly enhanced compared to conventional one‐pot and layer‐by‐layer approaches, owing to optimal spatial arrangement, increased surface area, and improved enzyme conformation. Furthermore, the encapsulated enzymes exhibit strong resistance to high temperatures, proteolysis, and organic solvents, along with excellent reusability, making this method highly promising for industrial biocatalytic applications.

Deciphering EU ‐ TIRADS : A Pictorial Guide to the Spectrum of Thyroid Nodules

ABSTRACT Thyroid nodules are frequently encountered in clinical practice, with ultrasound playing a central role in their initial evaluation and risk stratification. While most nodules are benign, distinguishing potentially malignant nodules is important. The EU‐TIRADS classification system, introduced in 2017, offers a simplified framework based on sonographic features such as composition, echogenicity, margins, shape, and echogenic foci. The classification is highly sensitive, with a good negative predictive value, particularly in nodules ≥ 10 mm. Its performance in nodules < 10 mm is less robust. Compared to the American College of Radiology's ACR‐TIRADS, which uses a point‐based system and generally results in fewer fine needle aspirations (FNAs), the use of EU‐TIRADS leads to more biopsies but captures more malignant nodules. Both systems have high sensitivity but modest specificity, with overlap in the features they assess. Key challenges remain, including inter‐observer variability and the interpretation of equivocal features such as vascularity and mild hypoechogenicity. Misleading appearances, often mimicking malignancy due to nodule scarring or retraction, further complicate assessment. While both EU‐TIRADS and ACR‐TIRADS offer valuable frameworks for clinical decision‐making, understanding their limitations and nuances is essential for accurate diagnosis and appropriate management of thyroid nodules. In this paper, we aim to explain thyroid nodule classification systems, with a specific focus on the EU‐TIRADS system.

Enhanced Electromagnetic Wave Absorption in Mapbi 3 Hybrid Perovskite Through a Defect‐Tunable Green Synthesis

Defect engineering and structure‐property relationship understanding in methylammonium lead iodide (MAPI) hybrid perovskites (HPs) attract significant scientific interest, as synthesis‐related defects may strongly influence intrinsic properties. We have explored a green solvent‐free synthesis—mechanosynthesis—leading to large quantities of MAPI powder with tuneable defect density suitable to study MAPI as an electromagnetic wave absorbing (EMWA) material. A dielectric loss enhancement was revealed at 11.4 GHz (X‐band) for 4 h‐ground MAPI powders (MAPI4h), compared to 30 min‐ground powders (MAPI30) when the particle size was <20 μm. MAPI powders display a fractal microstructure with agglomerates of clusters of (nano)grains (≈80 nm for MAPI4h), consisting further of oriented smaller nanograin (5–10 nm) clusters. A strong reabsorption in smaller particles was evidenced due to a surface‐defective layer. MAPI4h was shown to display a more surface‐defective layer with a higher defect density gradient from surface to (nano)grains core and unique open defects different from those in solution‐processed MAPI. These vacancy‐type surface defects would enhance dipole polarization by stabilizing methylammonium dipoles, thereby increasing permittivity. The improved dispersion of MAPI particles (<20 μm) in polymeric matrixes enhanced the surface effects and effective interactions with electromagnetic waves. This study demonstrated the potential of this green synthesis for producing large amount of HPs and tuning defects, opening new avenues for HPs EMWA application.

The PERPETUAL FLOWERING locus: Necessary but insufficient for genomic prediction of runnerless and other asexual reproduction phenotypes in strawberry

Abstract Strawberry ( Fragaria× $$ananassa ) reproduces sexually through seeds and asexually through stolons. The ability to cost‐effectively clonally propagate hybrid individuals on a large scale has shaped strawberry breeding and production practices. Despite the technical and economic importance of clonal propagation, little is known about the genetic regulation of runnering in strawberry, apart from the pleiotropic effects of PERPETUAL FLOWERING ( PF ), a dominant gene introgressed from a wild relative that abolishes temperature‐dependent photoperiod sensitivity and incompletely and variably suppresses runnering. Here, we show that runnering phenotypes are heritable and highly variable in strawberry, ranging from runnerless to prolific in short‐day ( pfpf ) and day‐neutral ( PF _) plants. The PF locus was physically mapped to Mb 26.4–27.3 on chromosome 4B and found to explain 22% of the genetic variance for runnering (78% of the heritability was missing). PF was the only runnering‐associated locus identified by genome‐wide association studies among diverse clonal genetic resources and progeny from narrow and wide crosses (1537 individuals). The pleotropic effect of PF on runnering was temporal, variable, and incompletely dominant. Genomic selection was found to be a viable strategy for modifying runnering phenotypes in strawberry. Genomic prediction accuracies ranged from 0.53 to 0.79 for runnering, were greater within than between populations, and increased when corrected for PF . Our study builds the foundation for improving the productivity of strawberry by developing runnerless cultivars for seed‐propagation or reduced runnering cultivars for clonal‐propagation through phenotypic or genomic selection.

Whole‐genome sequencing bulked segregant analysis uncovered FW7 , a Fusarium wilt resistance gene masked by epistasis in octoploid strawberry

Abstract Fusarium wilt, a vascular disease of strawberry ( Fragaria× $$ananassa ) caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. fragariae , has emerged over the past 20 years as a leading cause of severe plant wilt and death in California and many other parts of the world. We previously described several sources of resistance to race 1 of the pathogen; showed that resistance was conferred by dominant resistance genes ( R ‐genes) on chromosomes 2B ( FW1 , FW2 , and FW5 ), 1A ( FW3 ), and 6B ( FW4 ); and identified a cultivar (Earliglow) that was hypothesized to be a source of novel R ‐genes. EarliglowS 1 $_{1}}$ progeny segregated 15 resistant:1 susceptible (χ 2 = 0.03 ; p = 0.87 $\chi ^2 = 0.03; p = 0.87$ ), the Mendelian distribution expected when the phenotypes are caused by unlinked dominant duplicate epistasis. Here, we show that Earliglow carries a dominant R ‐gene ( FW6 ) in the FW1 cluster on chromosome 2B and an incompletely dominant R ‐gene ( FW7 ) on chromosome 2A, where Fusarium wilt R ‐genes have not been previously reported. The effect of FW7 was masked by the epistatic effect of FW6 ; this was determined by self‐pollinating anS 1 $_{1}}$ individual predicted to be homozygous for the recessive (susceptible) FW6 allele and heterozygous for FW7 alleles, creating and whole‐genome sequencing Fusarium wilt resistant and susceptibleS 2 $_{2}}$ bulks, and physically mapping the FW7 locus by bulked segregant analysis. Lastly, we identified candidate genes for FW7 , in addition to highly predictive FW6 ‐ and FW7 ‐associated SNPs for marker‐assisted selection of FW6 and FW7 alleles. This study laid the foundation for identifying the causal gene underlying FW7 and increasing the durability of resistance to Fusarium wilt by pyramiding FW7 with independent R ‐genes.

The Dementia Literacy Assessment (DeLA): A novel measure of Alzheimer's disease and related disorders health literacy in diverse populations

Multiple Concomitant Precipitating Factors of Hepatic Encephalopathy Are Associated With a Poor Prognosis in Patients With Cirrhosis Admitted to Intensive Care Unit

ABSTRACT Introduction Management of hepatic encephalopathy relies on the identification and control of precipitating factors (PF). The prognostic value of a PF is unknown, which we aimed to explore. Patients and Methods Single‐center retrospective study of cirrhotic patients included in a prospective cohort admitted to an intensive care unit (ICU) between 2019 and 2022. Inclusion criteria: cirrhosis; overt hepatic encephalopathy; ammonemia ≥ 50 μmol/L. PF considered: gastrointestinal bleeding, infection, acute renal injury (AKI), hyponatremia, constipation, non‐adherence to ammonia‐lowering therapy, TIPS, drugs precipitating overt hepatic encephalopathy. The primary endpoint was 1‐year transplant‐free survival (TFS). Secondary endpoint was recurrence of hepatic encephalopathy. Results 179/497 patients were included (men 72%, age 59, cause of cirrhosis alcohol (ALD)/metALD/MASLD/other in 41/21/6/32%, Child–Pugh A/B/C in 1/18/81%, West Haven grade 2/3/4 in 63/15/22%, MELD score 23). Reasons for admission were: gastrointestinal bleeding (31%), acute encephalopathy (28%), worsening liver function/jaundice (25%), infection (8%), and AKI (8%). All patients (100%) had at least one PF of hepatic encephalopathy (infection [64%], AKI [63%], drugs [41%], bleeding [36%], hyponatremia [22%], TIPS [12%], and constipation [1%]), and 82% had multiple concomitant PF. In‐hospital mortality was 50%, and median TFS was 0.8 months. In multivariate analysis, factors associated with death or liver transplantation were the number of PF, MELD and Child–Pugh scores, ACLF, AKI and infection. Hepatic encephalopathy reoccurred in 42% (median delay of 30 months). Conclusion All patients had precipitating factor of hepatic encephalopathy, 82% of them having multiple concomitant precipitating factors. Concomitant multiple precipitating factors were associated with death or liver transplantation. A systematic screening for all precipitating factors of hepatic encephalopathy should be proposed for cirrhotics admitted to intensive care unit.

Young Adult Patients With Paediatric‐Onset Inflammatory Bowel Disease Have a Higher Educational Level and a Higher Employment Rate Than the General Population

ABSTRACT Background & Aims There are few published data on the impact of paediatric‐onset inflammatory bowel diseases on education and employment. The objective of the present cross‐sectional study was to assess the educational level and occupational status of adult patients with paediatric‐onset inflammatory bowel diseases from the EPIMAD Registry. Methods The inclusion criteria were (i) a diagnosis of paediatric‐onset (< 17 years at diagnosis) inflammatory bowel diseases, and (ii) age 25 or over at the time of study. The patients answered a self‐questionnaire on their educational level and profession. The data were compared with those of the general population of the same age and geographic area. Results Three hundred and sixty‐one patients (286 with Crohn's disease and 75 with ulcerative colitis) filled out and returned the questionnaire. The median [interquartile] age was 15.0 [12.9; 16.3] years at diagnosis and 34.2 [29.6; 39.5] years at the time of the study. Patients were more likely to have a higher education degree than the general population (57% vs. 41%, p  < 0.0001). The unemployment rate was significantly lower among study participants than among the general population (9% vs. 15%, p  = 0.001). Salaried patients were significantly more likely to be employed in the healthcare sector (14% vs. 9% in the general population; p  = 0.005) and in the public sector (34% vs. 22% in the general population; p  < 0.0001). Conclusion Our results showed that relative to the general population, patients with paediatric‐onset inflammatory bowel diseases have a higher educational level and a higher employment rate, and are more likely to work in the healthcare and public sectors.