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23 pages, 2125 KB  
Article
Structural Integrity of Welded Pipe Joints Made of Creep–Resistant Steel P91 with Multiple Defects: Experimental Characterization and Engineering Critical Assessment
by Lazar Jeremić, Branislav Đorđević, Stefan Dikić, Aleksandar Jovanović, Aditya Rio Prabowo, Dorin Radu and Aleksandar Sedmak
Metals 2026, 16(10), 1121; https://doi.org/10.3390/met16101121 - 9 Oct 2026
Abstract
This study provides a comprehensive analysis of the mechanical properties and structural integrity of butt-welded P91 creep-resistant steel pipe joints utilized in high-pressure piping systems. Two pipe specimens with an outer diameter of Ø48.3 mm and a wall thickness of 10.15 mm were [...] Read more.
This study provides a comprehensive analysis of the mechanical properties and structural integrity of butt-welded P91 creep-resistant steel pipe joints utilized in high-pressure piping systems. Two pipe specimens with an outer diameter of Ø48.3 mm and a wall thickness of 10.15 mm were welded using the GTAW process in the PC position under controlled heat input, followed by post-weld heat treatment: one without and one with an axial misalignment of e = 1 mm (10% of wall thickness). Both welded pipes underwent an identical thermal cycle. Experimental results, including tensile testing, Charpy V-notch impact toughness at 20 °C, HV10 hardness testing, and macro/microstructural analysis, confirmed the over-matching effect of the W CrMo9-1 filler metal and satisfactory toughness in both the weld metal and heat-affected zone. The experimental data served as input parameters for Engineering Critical Assessment (ECA) using Failure Assessment Diagrams (FAD) according to the BS 7910 standard. The combined effect of multiple defects in welded joints—axial misalignment and a 0.3 mm root micro-crack (representing the lack of root penetration)—was evaluated under designed internal pressures of 200 and 300 bar. The results of the ECA approach indicate that the presence of multiple welding defects does not compromise the structural integrity of P91 welded pipes, provided that PWHT is properly executed. This underscores the critical role of the ECA/FAD methodology in evaluating the operational safety of high-pressure piping systems, as well as the need for thorough weldment characterization prior to service. Full article
(This article belongs to the Special Issue Recent Progress in Welding Technology for Metallic Materials)
32 pages, 2238 KB  
Review
Triokinase/FMN Cyclase: A Bifunctional Enzyme Linking Metabolism, Stress Responses and Disease
by João Meireles Ribeiro, Fernando Martín-Ruiz and José Carlos Cameselle
Biology 2026, 15(19), 1764; https://doi.org/10.3390/biology15191764 - 3 Oct 2026
Viewed by 128
Abstract
Triokinase/FMN cyclase (TKFC) is a bifunctional enzyme that catalyzes both ATP-dependent triose phosphorylation and the formation of riboflavin 4′,5′-cyclic phosphate (cFMN) from FAD, thereby linking fructose and flavin metabolism through a single protein. Structural modeling supports a model of TKFC as a conformationally [...] Read more.
Triokinase/FMN cyclase (TKFC) is a bifunctional enzyme that catalyzes both ATP-dependent triose phosphorylation and the formation of riboflavin 4′,5′-cyclic phosphate (cFMN) from FAD, thereby linking fructose and flavin metabolism through a single protein. Structural modeling supports a model of TKFC as a conformationally dynamic homodimer in which interacting K and L domains cooperate through composite intersubunit active sites to support both kinase and cyclase reactions. Beyond its classical role in fructose metabolism, TKFC has emerged as a determinant of fructose-derived carbon partitioning and has been implicated in nutrient sensing, oxidative stress adaptation, innate immunity, ferroptosis and several inherited human disorders. Recent biochemical and analytical studies have renewed interest in cFMN as a bona fide metabolite and provide evidence consistent with cFMN synthesis and degradation, while its physiological turnover remains to be established. Here, we review the historical development, structural organization, catalytic mechanisms and expanding biological functions of TKFC, highlighting its links with intermediary metabolism, cellular stress adaptation and human disease. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
24 pages, 6844 KB  
Review
‘’Not a Universal Effect’’: Polyunsaturated Fatty Acids and Cognition from Pregnancy to Adolescence—A Narrative Review and Nutritional Guidance for a Mediterranean Population
by Elissar El-Hayek, Marguerita Akiki, Marie-Joelle Chbat, Rita Keyrouz, Celine Mrad, Marc Bouji and Yonna Sacre
Nutrients 2026, 18(19), 3264; https://doi.org/10.3390/nu18193264 - 3 Oct 2026
Viewed by 173
Abstract
Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are an important class of bioactive lipid mediators, essential for brain development from gestation through adolescence. Yet human studies evaluating the benefits of PUFAs for cognition remain inconsistent. This narrative review [...] Read more.
Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are an important class of bioactive lipid mediators, essential for brain development from gestation through adolescence. Yet human studies evaluating the benefits of PUFAs for cognition remain inconsistent. This narrative review synthesizes studies from PubMed, Scopus, and Google Scholar examining PUFA intake, status, and supplementation in relation to cognitive and neurodevelopmental outcomes. It uses a thematic approach rather than the systematic search and screening protocol of a systematic review. This review also discusses the genetic determinants of PUFA metabolism and their association with neurodevelopmental outcomes, in addition to nutritional recommendations for Lebanon, a Mediterranean country. Animal models consistently show neuroprotective and anti-inflammatory effects of omega-3 PUFAs during critical windows of brain development. However, evidence from human studies evaluating the cognitive benefits of PUFAs remains limited and inconsistent, with more pronounced benefits in specific populations with low baseline PUFA status, learning difficulties, ADHD, or preterm birth. Genetic variation in genes involved in PUFA metabolism such as FADS1, FADS2, and ELOVL2/5 affects the capacity to synthesize long-chain PUFAs from dietary precursors, helping explain variability in response to omega-3 supplementation. Lebanon’s traditional Mediterranean diet already supplies PUFAs and MUFAs; the real challenge is improving adherence to it through nutrition education and policy. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids in Human Health and Disease)
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20 pages, 5264 KB  
Article
Integrated Transcriptome–Translatome Analysis Reveals Translational Buffering in the Liver of Chickens Infected with Fowl Adenovirus Serotype 4 Strain GXYL-03, a Strain with Reduced Virulence
by You Wei, Qing Fan, Zhixun Xie, Xiaofeng Li, Sheng Wang, Bingyi Yang, Yanfang Zhang, Lijun Wan, Aiqiong Wu, Hongyu Ren, Zuoxin Chen, Liji Xie, Meng Li, Tingjun Hu and Sisi Luo
Microorganisms 2026, 14(10), 2226; https://doi.org/10.3390/microorganisms14102226 - 2 Oct 2026
Viewed by 119
Abstract
Fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium-hepatitis syndrome (HHS) and has resulted in severe economic losses to the poultry industry in China since 2015. In this study, we isolated a naturally occurring strain with reduced virulence designated GXYL-03, which caused no gross or [...] Read more.
Fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium-hepatitis syndrome (HHS) and has resulted in severe economic losses to the poultry industry in China since 2015. In this study, we isolated a naturally occurring strain with reduced virulence designated GXYL-03, which caused no gross or histological HHS lesions in 4-week-old specific pathogen-free (SPF) chickens infected at 106 TCID50, whereas clinical signs and partial mortality were observed at higher doses of 107–108 TCID50. After a single immunization with 5 × 104 TCID50 of GXYL-03, all ten immunized SPF chickens survived throughout the 14-day observation following lethal GX2017-005 challenge, whereas all ten challenge-control chickens died. Integrated transcriptome and translatome analyses were performed on the livers of chickens infected with FAdV-4 strains of differing virulence by RNA sequencing (RNA-seq) and polysome profiling, with three biological replicates per group. The polysome/non-polysome (P/NP) ratio did not differ significantly among groups (p > 0.05), indicating stable global translation flux. The GXYL-03 group had 2,131 transcriptomic differentially expressed genes (DEGs) but only 71 translatomic DEGs; the GX2017-005 group had 7767 and 148, respectively, indicating that only 3.3% and 1.9% of transcriptional perturbations were transmitted to translation, revealing a pronounced translational buffering effect. Translation efficiency (TE) changes were predominantly suppressive, and downregulated genes accounted for 58.6% and 61.8% of TE changes in the two strains. The functional enrichment of genes whose expression was synchronously upregulated at both levels (TE+RNA+) revealed that GXYL-03 was enriched mainly in protein-coding genes involved in cellular stress, DNA damage repair, vesicle transport, and protein homeostasis (HSPA2, HSPB9, FANCD2, EHD2, and Vault), whereas GX2017-005 was enriched in liver injury-related genes (CD74, ATG2B, FKBP5, ND1, and COX1) that were not differentially expressed in GXYL-03. This study provides insights into the development of FAdV-4 strains with reduced virulence and virus–host interactions. Full article
(This article belongs to the Section Veterinary Microbiology)
14 pages, 2907 KB  
Article
Detection of Avian Infectious Bronchitis Virus Genotype GI-13 in the Almaty Region, Kazakhstan
by Karina Ivanova, Marina Kopochenya, Dinara Naizabayeva and Andrey Zhigailov
Microbiol. Res. 2026, 17(10), 195; https://doi.org/10.3390/microbiolres17100195 - 1 Oct 2026
Viewed by 122
Abstract
Infectious bronchitis remains one of the most economically significant viral diseases in commercial poultry farming, despite the widespread implementation of vaccination programs. The high genetic variability of the infectious bronchitis virus (IBV) leads to the emergence of genetically and antigenically diverse variants, including [...] Read more.
Infectious bronchitis remains one of the most economically significant viral diseases in commercial poultry farming, despite the widespread implementation of vaccination programs. The high genetic variability of the infectious bronchitis virus (IBV) leads to the emergence of genetically and antigenically diverse variants, including vaccine-related and field variants detected in vaccinated flocks. This study presents a molecular genetic analysis of an IBV variant detected in 2025 at a poultry farm in the Almaty region of Kazakhstan. Samples were collected from seven 35-day-old deceased chickens during an episode of mortality. The reported clinical presentation included diarrhea and signs described as hepatitis, without pronounced respiratory manifestations. Initial molecular screening followed by amplicon sequencing confirmed the presence of IBV RNA in these clinical samples. For detailed genotyping and assessment of genetic variability, an 858-nucleotide fragment of the S1 gene was analyzed. Phylogenetic analysis showed that the detected virus belongs to genotype GI-13 and clusters with the 4/91 vaccine lineage while possessing distinct nucleotide substitutions. Comparison with the 4/91 reference strain identified 17 variable nucleotide positions, including two synonymous and 15 non-synonymous changes, corresponding to 10 unique amino acid substitutions. Broader molecular screening also detected avian leukosis virus (ALV) genotype E and fowl adenovirus type 5 (FAdV-5), whereas the other tested pathogens were not detected. These findings demonstrate the genetic distinctness of the detected GI-13 virus from the 4/91 vaccine reference; however, the available data cannot establish its origin, pathogenic significance, persistence, or sustained circulation. The findings underscore the value of continued molecular surveillance and sequence-based characterization of IBV in vaccinated poultry. Full article
(This article belongs to the Section Medical and Veterinary Microbiology)
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13 pages, 1895 KB  
Review
Riboflavin as a Regulator of Cellular Metabolism: From the Classic Vitamin B2 to a Key Redox Factor
by Julia Kaźmierczak-Barańska, Krzysztof Halczuk and Bolesław T. Karwowski
Nutrients 2026, 18(19), 3223; https://doi.org/10.3390/nu18193223 - 29 Sep 2026
Viewed by 151
Abstract
Riboflavin, i.e., vitamin B2, was first isolated by Kuhn and Győrgy in 1933, who reported that it acts as a growth factor. Riboflavin has long been known to play a key role in energy metabolism and cellular respiration, and its deficiency negatively affects [...] Read more.
Riboflavin, i.e., vitamin B2, was first isolated by Kuhn and Győrgy in 1933, who reported that it acts as a growth factor. Riboflavin has long been known to play a key role in energy metabolism and cellular respiration, and its deficiency negatively affects skin and mucous membrane health. More recent studies have found it to regulate mitochondrial metabolism and to serve as the core of flavin coenzymes (FAD, FMN), which enable the respiratory chain and β-oxidation. Riboflavin also plays a key role as an antioxidant. While it is not a classic free antioxidant, it supports the enzymatic antioxidant system by supporting glutathione reductase, thioredoxin reductase, and ROS neutralization. On the other hand, when exposed to light, riboflavin exhibits photosensitizing properties that generate reactive oxygen species. As a result, it can initiate oxidative processes involving lipids, proteins, and nucleic acids, thereby exhibiting a prooxidative effect. The aim of this review is to provide an overview of the current understanding of the role of riboflavin in cellular and human health. Full article
(This article belongs to the Section Micronutrients and Human Health)
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17 pages, 416 KB  
Article
Impact of Fish Meal Replacement with Meat Meal on the Growth and Fillet Nutritional Quality of Chum Salmon (Oncorhynchus keta)
by Seong-Mok Jeong, Jinho Bae, Min-Gi Kim, June Kim, Daehyun Ko, Hye Jeong Park, Tae Sook Na and Mi-Soon Jang
Foods 2026, 15(19), 3475; https://doi.org/10.3390/foods15193475 - 28 Sep 2026
Viewed by 171
Abstract
Rendered animal by-products such as meat meal are promising fish meal alternatives owing to their high protein content; however, they contain little n-3 long-chain polyunsaturated fatty acids (LC-PUFA), whose effects on fillet fatty acid quality and endogenous LC-PUFA biosynthesis in chum salmon ( [...] Read more.
Rendered animal by-products such as meat meal are promising fish meal alternatives owing to their high protein content; however, they contain little n-3 long-chain polyunsaturated fatty acids (LC-PUFA), whose effects on fillet fatty acid quality and endogenous LC-PUFA biosynthesis in chum salmon (Oncorhynchus keta) remain unclear. We evaluated the growth, fillet fatty acid composition, and hepatic gene expression of chum salmon fed four diets—a control with 50% fish meal (D1), diets with 35% or 20% fish meal and the remainder replaced by meat meal (D2 and D3), and a D3-like diet with reduced fish oil (D4). Growth performance and feed utilization were unaffected, whereas the hepatosomatic index decreased as meat meal inclusion increased. Muscle n-3 LC-PUFA decreased with fish meal replacement but did not differ between D3 and D4. Serum non-specific immune parameters were unaffected, whereas serum GPx and catalase activities were lowest in fish fed D3. Although srebf1 (sterol regulatory element-binding transcription factor 1) expression increased at the highest replacement level, fads2 (fatty acid desaturase 2) and elovl5 (elongation of very long-chain fatty acids protein 5) were not upregulated, indicating that the reduced n-3 LC-PUFA supply was not compensated by endogenous biosynthesis. Overall, meat meal can replace up to 60% of fish meal without compromising growth, but adequate dietary n-3 LC-PUFA should be maintained to preserve fillet quality. Full article
(This article belongs to the Special Issue Food Safety and Quality in Aquaculture and Fisheries Products)
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24 pages, 4598 KB  
Article
Integrated Multi-Omics Reveals Disruption of Lipid–Steroid Regulatory Axis Underlying Chronic Heat Stress-Induced Ovarian Dysfunction in Mice
by Farwa Nazir, Muhammad Ammar Baibrus, Muhammad Tariq, Mohamed Tharwat, Shiyuan Pei, Yang Wen, Jie Shen, Meilian Su, Qiuxia Liang, Guangbin Zhou, Fahad A. Alshanbari and Guozhi Yu
Int. J. Mol. Sci. 2026, 27(19), 8671; https://doi.org/10.3390/ijms27198671 - 28 Sep 2026
Viewed by 166
Abstract
Heat stress is an escalating environmental challenge that adversely affects mammalian reproductive physiology, yet the integrated molecular mechanisms through which ovarian tissue responds to sustained heat stress remain incompletely understood. This study investigated the effects of chronic heat stress on mouse ovarian tissue [...] Read more.
Heat stress is an escalating environmental challenge that adversely affects mammalian reproductive physiology, yet the integrated molecular mechanisms through which ovarian tissue responds to sustained heat stress remain incompletely understood. This study investigated the effects of chronic heat stress on mouse ovarian tissue using an integrated multi-omics approach. Female C57BL/6 mice were exposed to heat stress at 42 °C for 20 min daily over 30 days. Whole ovarian tissues were subsequently analyzed using RNA sequencing, DIA-based proteomics, untargeted metabolomics, histological examination, and RT-qPCR validation. Histological analysis showed a significant reduction in secondary follicle profiles in heat-stressed mice, whereas primary and antral follicle profiles showed inter-animal variability and did not differ significantly between groups. Transcriptomic and proteomic analyses identified altered expression of lipid metabolism- and steroidogenesis-related molecules, including Apoa1, Apoa2, Lpl, Fads2, and Hsd17b2. Metabolomic profiling further showed marked changes in metabolites related to lipid metabolism and steroid hormone biosynthesis. Integrated pathway analysis revealed recurrent enrichment of pathways associated with lipid metabolism and endocrine regulation, particularly PPAR signaling, cholesterol metabolism, and steroid hormone biosynthesis. RT-qPCR validation confirmed altered expression of selected genes involved in lipid transport and steroidogenic pathways. These findings suggest that chronic heat stress may disrupt ovarian metabolic and endocrine homeostasis through alterations in lipid–steroid regulatory pathways. This study provides systems-level evidence supporting the involvement of interconnected metabolic pathways in heat stress-associated ovarian dysfunction. Full article
(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)
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32 pages, 16638 KB  
Article
A Draft Genome Assembly of Argania spinosa Provides Insights into Lipid Metabolism-Associated Genes and Repeat-Rich Genome Architecture
by My Abdelmajid Kassem, Naoufal Lakhssassi, Dounya Knizia, Abdelhamid El Mousadik and Khalid Meksem
Plants 2026, 15(19), 2945; https://doi.org/10.3390/plants15192945 - 26 Sep 2026
Viewed by 229
Abstract
Argania spinosa (L.) Skeels is an ecologically and economically important Moroccan tree valued for its oil-rich seeds and adaptation to arid environments. Here, we generated and characterized a genotype-specific draft genome assembly of Z-AL-IV-13 using approximately 82.7 GB of Illumina sequencing data. The [...] Read more.
Argania spinosa (L.) Skeels is an ecologically and economically important Moroccan tree valued for its oil-rich seeds and adaptation to arid environments. Here, we generated and characterized a genotype-specific draft genome assembly of Z-AL-IV-13 using approximately 82.7 GB of Illumina sequencing data. The final contamination-screened assembly comprised 584.21 Mb across 139,591 sequences, with an N50 of 6.84 kb. BUSCO analysis identified 59.1% complete, 25.4% fragmented, and 15.6% missing conserved eudicot orthologs, while independent k-mer analyses indicated incomplete genome representation and substantial repetitive sequence. Comparative whole-genome alignments showed that 95.34–97.60% of the represented Z-AL-IV-13 assembly sequence aligned to five published A. spinosa assemblies, indicating high sequence correspondence among represented regions. Protein-supported annotation identified 44,777 transcript models, of which 37,507 (83.77%) produced significant Swiss-Prot matches. RepeatMasker identified 37.73% of the assembly as repetitive, predominantly unclassified interspersed repeats. Targeted homology analyses identified assembly loci associated with fatty-acid and triacylglycerol metabolism, including ACCase components, KAS, SACPD, FAD2, GPAT, LPAT/LPAAT, DGAT, PDAT, and acyl-ACP thioesterase families. These sequence-based assignments identify candidate lipid-metabolism-associated homologs but do not establish pathway completeness, biochemical function, or definitive gene-copy numbers. Overall, Z-AL-IV-13 provides an independently generated, genotype-specific draft genomic resource that complements chromosome-scale A. spinosa references while retaining the limitations associated with assembly fragmentation and incomplete gene-space recovery. Full article
(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)
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29 pages, 615 KB  
Article
Validation of the Hungarian FAD-GF and BAFFS in a Multi-Informant Clinical Sample of Families of Adolescents
by Noémi Gyenis-Kátay, Ildikó Danis, Klára Soltész-Várhelyi, András Szauer and Szabolcs Török
Behav. Sci. 2026, 16(10), 1753; https://doi.org/10.3390/bs16101753 - 25 Sep 2026
Viewed by 306
Abstract
Family functioning is central to youth adaptation, yet brief measures require validation across informants and clinical contexts. This study evaluated the Hungarian 12-item Family Assessment Device–General Functioning Scale (FAD-GF) and the three-item Brief Assessment of Family Functioning Scale (BAFFS) in 562 respondents from [...] Read more.
Family functioning is central to youth adaptation, yet brief measures require validation across informants and clinical contexts. This study evaluated the Hungarian 12-item Family Assessment Device–General Functioning Scale (FAD-GF) and the three-item Brief Assessment of Family Functioning Scale (BAFFS) in 562 respondents from 213 families of adolescents with autism spectrum disorder (ASD), anorexia nervosa (AN), or diabetes mellitus (DM). Analyses included cluster-adjusted ordinal confirmatory and multigroup CFA, exploratory factor and general-factor analyses, internal-consistency estimation, and cluster-robust external-association tests. Prespecified FAD-GF models showed inadequate fit, but exploratory analyses indicated a dominant general factor accompanied by recurring local dependencies. An exploratory one-factor model with seven simultaneously estimated residual covariances showed broadly acceptable fit (CFI = 0.962, TLI = 0.946, RMSEA = 0.078, SRMR = 0.034). Internal consistency was high for the FAD-GF (α = 0.893, ωT = 0.896) and acceptable for the BAFFS (α = 0.747, ωT = 0.756). The FAD-GF supported partial scalar invariance across parents and adolescents, strict invariance across fathers and mothers, and scalar but not strict invariance across ASD and AN parents. The BAFFS supported scalar but not strict invariance across fathers and mothers and metric but not scalar invariance across ASD and AN parents; adolescent-group solutions were inadmissible, and its just-identified CFA could not test unidimensionality. Both scales showed expected associations with stress, well-being, relationship satisfaction, and coping. The findings support use of the FAD-GF total score, whereas the BAFFS is better retained as a brief observed index, particularly in parental reports, pending further cross-group validation. Full article
(This article belongs to the Section Health Psychology)
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33 pages, 19992 KB  
Article
LRRK2 Kinase Inhibitor PF-06447475 Protects Against Alzheimer’s Disease-Associated Pathology in PSEN1 I416T Cholinergic-like Neurons
by Nicolas Gomez-Sequeda, Marlene Jimenez-Del-Rio and Carlos Velez-Pardo
Kinases Phosphatases 2026, 4(3), 27; https://doi.org/10.3390/kinasesphosphatases4030027 - 18 Sep 2026
Viewed by 176
Abstract
Familial Alzheimer’s disease (FAD) is an accelerated form of dementia affecting cholinergic neurons. Despite several efforts, no single drug or treatment has demonstrated complete efficacy. Therefore, finding effective therapeutic agents is imperative. Previous studies have shown that the PSEN1 I416T variant induces FAD-like [...] Read more.
Familial Alzheimer’s disease (FAD) is an accelerated form of dementia affecting cholinergic neurons. Despite several efforts, no single drug or treatment has demonstrated complete efficacy. Therefore, finding effective therapeutic agents is imperative. Previous studies have shown that the PSEN1 I416T variant induces FAD-like neuropathology in cholinergic-like neurons (ChLNs), characterized by the intracellular accumulation of the Aβ (iAβ) peptide, the oxidation of the stress sensor protein DJ-1, the abnormal phosphorylation of the tau protein at serine 202/threonine 205 (pS202/T205), the loss of mitochondrial membrane potential (ΔΨm), and activation of the pro-apoptotic proteins tumor protein 53 (TP53), Jun proto-oncogene, AP-1 transcription factor subunit (c-JUN), p53 upregulated modulator of apoptosis (PUMA), and cleaved caspase-3 (CC3). We report for the first time that PSEN1 I416T induces abnormal phosphorylation of Leucine-rich repeat kinase 2 (LRRK2) kinase at residue serine 935 (S935), concomitant with phosphorylated alpha-synuclein (αSYN) at residue serine 129 (S129) and abnormal accumulation of autophagosomes and atypical increase in vesicular lysosomal pH, thereby provoking a profound alteration in autophagy in ChLNs. Here, we also demonstrate for the first time that the potent LRRK2 inhibitor PF-06447475 (hereafter referred to as PF475) almost completely attenuated PSEN1 I416T-induced proteinopathy, oxidative stress (OS), and apoptosis and improve autophagy to an activity comparable to untreated wild-type (WT) ChLNs. Overall, PF475 restored the survival of mutant ChLNs. Taken together, these findings suggest that PF475 is an excellent pharmacological tool with which to investigate the regulation of LRRK2-associated pathological signaling in the PSEN1 I416T familial Alzheimer’s disease (FAD) model. Full article
(This article belongs to the Special Issue Kinases and Phosphatases in Alzheimer's Disease)
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18 pages, 5311 KB  
Article
The Flexible Peripheral Segments Modulate the Catalytic Activity of the FAD-Containing Monooxygenase EthA from Mycobacterium tuberculosis
by Dafeng Liu, Xieping Sun, Feng Yu, Hongying Song, Wenshuang Yao, Huashui Deng and Daoqi Song
Biomolecules 2026, 16(9), 1333; https://doi.org/10.3390/biom16091333 - 14 Sep 2026
Viewed by 375
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern, particularly due to the emergence of drug-resistant strains. FAD-containing monooxygenase EthA activates the antitubercular prodrug ethionamide (ETH) in Mtb. However, the structural and functional mechanisms of Mtb [...] Read more.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern, particularly due to the emergence of drug-resistant strains. FAD-containing monooxygenase EthA activates the antitubercular prodrug ethionamide (ETH) in Mtb. However, the structural and functional mechanisms of Mtb EthA are not fully understood. Here, we report an AlphaFold2-predicted structural model of Mtb EthA, validated using Ramachandran analysis (91.7% residues in favored regions) and a ProSA Z-score of −10.96. Based on the results of molecular docking, site-directed mutagenesis was conducted. We found that R207 is required for EthA activity. Alanine substitutions at T186, S208, and T210 resulted in 5.8- to 7.2-fold reductions in activity. Conversely, deletion of three peripheral segments (residues 137–176, 315–336, and 419–460) enhanced activity by 1.9-, 1.5-, and 1.2-fold, respectively. These results provide a structural framework for EthA function and suggest that flexible peripheral regions may constrain catalytic activity, offering insights into ETH activation and potential mechanisms of drug resistance. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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16 pages, 2761 KB  
Article
Calcium-Triggered PuMYB44-PuERF118 Cascade Activates PuFAD8 to Promote Aroma Biosynthesis in Pear Fruit
by Xinyu Wang, Gaifang Yao, Min Zhang, Huihui Song, Zhen Cao, Kangdi Hu, Xinxin Gai, Hua Zhang and Gaihua Qin
Int. J. Mol. Sci. 2026, 27(18), 8070; https://doi.org/10.3390/ijms27188070 - 10 Sep 2026
Viewed by 293
Abstract
Fruit aroma is a key factor shaping the commercial value of pears. MYB and ERF transcription factors (TFs) are involved in regulating the biosynthesis of fruit aroma compounds, yet the mechanisms underlying their synergistic regulation of pear aroma formation remain elusive. Calcium signaling [...] Read more.
Fruit aroma is a key factor shaping the commercial value of pears. MYB and ERF transcription factors (TFs) are involved in regulating the biosynthesis of fruit aroma compounds, yet the mechanisms underlying their synergistic regulation of pear aroma formation remain elusive. Calcium signaling exerts an important role in fruit aroma biosynthesis; nevertheless, how calcium signaling mediates MYB-ERF transcription factors to participate in pear aroma biosynthesis remains unclear. Here, transcriptomic profiling of calcium-treated pear fruits screened two significantly upregulated TFs, PuMYB44 and PuERF118, as candidate genes. Phylogenetic analysis and conserved domain characterization further suggested that these two genes may be involved in regulating fatty acid biosynthesis. Transient overexpression experiments in pear fruits revealed that the co-expression of PuMYB44 and PuERF118 synergistically activated a set of fatty acid biosynthesis genes, including PuFAD2, PuFAD3, PuFAD8, PuLOX5, PuLOX21, and PuSCD. Meanwhile, the co-expression markedly increased the contents of key aroma volatiles, such as ethyl acetate, 1-hexanol, ethyl 2-methylbutyrate and hexadecane. Yeast two-hybrid and luciferase complementation assays confirmed an interaction between PuMYB44 and PuERF118. Analysis of the PuFAD8 promoter sequence revealed a conserved MYB-binding motif and an ERF-responsive cis-acting element. Dual-luciferase reporter assays further confirmed that both PuMYB44 and PuERF118 can independently activate PuFAD8 transcription, and that the synergistic activation effect resulting from the co-expression of these two factors is significantly stronger than that observed when either factor is expressed alone. In summary, this study elucidated a calcium-responsive transcriptional module underlying the biosynthesis of pear aroma and provided potential molecular targets for improving the flavor quality of pear fruit. Full article
(This article belongs to the Special Issue Molecular Research in Postharvest Biology)
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19 pages, 5356 KB  
Article
Maternal Antibody Transfer of a Fiber-Based Subunit Vaccine Confers Complete Protection Against Fowl Adenovirus Serotype 11 in Neonatal Chickens
by Guopan Li, Sirong Gao, Xiaoyang Ai, Jun Rong, Disi Chen, Lianshen Cai and Weiwei Guo
Vet. Sci. 2026, 13(9), 928; https://doi.org/10.3390/vetsci13090928 - 9 Sep 2026
Viewed by 335
Abstract
Fowl adenovirus serotype 11 (FAdV-11) is an emerging pathogen associated with inclusion body hepatitis (IBH) and high mortality in commercial broilers. In this study, we evaluated the protective efficacy of maternal antibody transfer against FAdV-11 in neonatal chicks. A hypervirulent FAdV-11 strain (FAdV-11/HB2022/1), [...] Read more.
Fowl adenovirus serotype 11 (FAdV-11) is an emerging pathogen associated with inclusion body hepatitis (IBH) and high mortality in commercial broilers. In this study, we evaluated the protective efficacy of maternal antibody transfer against FAdV-11 in neonatal chicks. A hypervirulent FAdV-11 strain (FAdV-11/HB2022/1), isolated from an IBH outbreak in Hubei Province, China, caused 90% mortality in 1-day-old specific-pathogen-free (SPF) chickens; 7-day-old chicks exhibited no mortality but developed mild hepatic lesions and sustained viral replication. A soluble, trimeric Fiber subunit vaccine (Fiber282–569) was developed through rational truncation of the transmembrane domain, retaining both the shaft and head domains, with its homotrimeric conformation confirmed by size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS). Immunization of breeder hens with Fiber282–569 elicited high titers of FAdV-11-specific IgY and neutralizing antibodies that were efficiently transferred to progeny via the egg yolk. Upon lethal challenge with FAdV-11/HB2022/1, 1-day-old progeny chicks from vaccinated breeders exhibited 100% survival with no clinical signs, no gross pathological lesions, and undetectable viral loads in liver tissues, demonstrating complete protection. In contrast, all chicks from unvaccinated breeders succumbed within 5 days post-infection. These results demonstrate that maternal antibody transfer of the fiber-based subunit vaccine confers complete protection against lethal FAdV-11 infection in neonatal chicks, providing a safe and effective candidate strategy for controlling FAdV-11 in the poultry industry. Full article
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Article
Effect of High Temperature and Drought on the Fatty Acid Composition of Oil of Different Linseed Varieties and Its Association with Gene Expression
by Gleb N. Vladimirov, Sergey V. Osipenko, Liubov V. Povkhova, Anton A. Bashilov, Yury I. Kostyukevich, Eugene N. Nikolaev, Tatiana A. Rozhmina, Aleksey A. Gryzunov, Elizaveta A. Ivankina, Ekaterina M. Dvorianinova, Arthur G. Yablokov, Elena V. Borkhert, Alexander A. Arkhipov, Elena N. Pushkova, Alexey A. Dmitriev and Nataliya V. Melnikova
Int. J. Mol. Sci. 2026, 27(18), 8006; https://doi.org/10.3390/ijms27188006 - 9 Sep 2026
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Abstract
Flax is an important food and industrial crop. Linolenic acid (LIN) content of linseed oil differs greatly among varieties, ranging from 2% to 70%. In addition to genetic factors, environmental conditions can also significantly impact the fatty acid composition of linseed oil. Our [...] Read more.
Flax is an important food and industrial crop. Linolenic acid (LIN) content of linseed oil differs greatly among varieties, ranging from 2% to 70%. In addition to genetic factors, environmental conditions can also significantly impact the fatty acid composition of linseed oil. Our study aimed to compare the effects of different temperature and watering conditions on the fatty acid composition of oil from nine flax varieties with diverse LIN content induced by genotype. Elevated temperature with reduced watering resulted in increased oleic acid (OLE) levels in all varieties. Decreases in linoleic acid (LIO) and LIN were also observed, though these trends were less pronounced in genotypes with low LIN content. Using our previously obtained transcriptomic data for seeds of the same flax varieties grown under the same conditions, we found that elevated temperature with reduced watering caused the maximum expression levels to shift to earlier development stages and shortened the period of high expression for the key fatty acid desaturase (FAD) genes: FAD2a-1, FAD2a-2, and FAD2b-2 (OLE to LIO desaturation) as well as FAD3a and FAD3b (LIO to LIN desaturation). However, low-LIN flax genotypes have inactivating mutations in FAD3a and FAD3b, so FAD3d-1, FAD3d-2, FAD3c-1, and FAD3c-2 were likely the major contributors to LIN synthesis in these varieties. These FAD3 genes had low but relatively stable expression levels during seed development compared to FAD3a and FAD3b, which may explain why growth conditions had less effect on LIN content in low-LIN genotypes. High temperature with optimal watering also led to a significant increase in OLE content in flax seeds. Thus, the fatty acid composition of linseed oil is significantly altered at high temperature, which is associated with a shift to earlier stages and narrowing of the expression peaks of key FAD genes in seeds. These findings should be considered when cultivating flax and producing pharmaceuticals, food, paints, and other products from its seeds. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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