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21 pages, 9783 KB  
Article
Leucine-Rich Repeat Extension 7 Gene Confers Cotton Resistance to Verticillium Wilt
by Xue Du, Yanfang Li, Wankui Gong, Zhen Wei, Qiankun Liu, Aiming Zhang, Yuting Ge, Yangyang Wei, Yuling Liu, Quanwei Lu, Xianghui Xiao, Pengtao Li, Juwu Gong and Renhai Peng
Int. J. Mol. Sci. 2026, 27(9), 3852; https://doi.org/10.3390/ijms27093852 (registering DOI) - 26 Apr 2026
Abstract
Leucine-rich repeat extensins (LRXs) are essential regulators of plant development, cell wall integrity, and stress responses. However, genome-wide LRX studies in cotton are limited. Analysis of four Gossypium species identified 29, 28, 16, and 16 LRX genes in G. hirsutum, G [...] Read more.
Leucine-rich repeat extensins (LRXs) are essential regulators of plant development, cell wall integrity, and stress responses. However, genome-wide LRX studies in cotton are limited. Analysis of four Gossypium species identified 29, 28, 16, and 16 LRX genes in G. hirsutum, G. barbadense, G. arboreum, and G. raimondii, respectively. Phylogenetic analysis resolved these 89 genes into four subfamilies (I–IV). Structural annotation revealed that cotton LRX family members exhibit conserved domain architectures. This finding was corroborated by motif analysis, which revealed notable conservation in the motif compositions of most cotton LRX proteins, suggesting functional conservation across evolutionary lineages. Distinct spatiotemporal expression patterns were uncovered between G. hirsutum and G. barbadense. Prolonged exposure to extreme temperatures induced widespread down-regulation of most GhLRX genes, whereas genes in subgroup IV were significantly up-regulated under salt and drought stress conditions, respectively. Notably, GhLRX7 showed a more proactive responding profile to Verticillium wilt (VW) infection, which was therefore selected for functional validation employing virus-induced gene silencing in the cotton cultivars MBI9626 and CCRI36. Phenotypic analysis of silenced plants revealed exacerbated disease symptoms compared to wild-type controls, providing direct evidence implicating GhLRX7 as a key contributor to defense against VW. Full article
(This article belongs to the Section Molecular Plant Sciences)
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15 pages, 2585 KB  
Article
Hydrogen Sulfide Primes bZIP68 via Persulfidation to Enhance Redox-Dependent Transcription and Adaptation to Osmotic Stress in Rice
by Xiaoyun Ma, Fengchao Zhai, Lingxi Geng, Guojing Chen, Wenge Li, Mohammad Saidur Rhaman, Jing Zhang, Yanjie Xie and Heng Zhou
Int. J. Mol. Sci. 2026, 27(9), 3841; https://doi.org/10.3390/ijms27093841 (registering DOI) - 26 Apr 2026
Abstract
Osmotic stress limits rice productivity, yet the crosstalk between hydrogen sulfide signaling and redox regulation remains incompletely understood. We previously showed that redox-dependent oligomerization of the basic (region) leucine zippers transcription factor bZIP68 at Cys245 confers osmotic tolerance. However, the role of an [...] Read more.
Osmotic stress limits rice productivity, yet the crosstalk between hydrogen sulfide signaling and redox regulation remains incompletely understood. We previously showed that redox-dependent oligomerization of the basic (region) leucine zippers transcription factor bZIP68 at Cys245 confers osmotic tolerance. However, the role of an adjacent cysteine, Cys171, was undefined. Here, we demonstrate that osmotic stress induces persulfidation of bZIP68 specifically at Cys171. This modification facilitates Cys245-mediated oxidation-dependent oligomerization, thereby enhancing bZIP68 transcriptional activity toward COLD-REGULATED413-THYLAKOID MEMBRANE1 (COR413-TM1). Transgenic complementation and physiological assays confirmed that Cys171 persulfidation is essential for full bZIP68 function in osmotic adaptation. Transcriptomic analysis further revealed that Cys171 is required for bZIP68-driven transcriptional reprogramming under stress. Our findings establish a hierarchical redox cascade wherein persulfidation primes bZIP68 for oxidative activation, highlighting a regulatory crosstalk between distinct post-translational modifications. These mechanistic insights expand our understanding of H2S signaling and identify the bZIP68 cysteine network as a potential target for improving crop stress resilience. Full article
(This article belongs to the Collection Advances in Molecular Plant Sciences)
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18 pages, 2697 KB  
Article
Complete Mitochondrial Genomes and Evolutionary Insights of Two Commercially Farmed Edible Crickets (Gryllus bimaculatus and Teleogryllus mitratus) from Thailand
by Pannapak Urairut, Yash Munnalal Gupta and Somjit Homchan
Animals 2026, 16(9), 1305; https://doi.org/10.3390/ani16091305 - 23 Apr 2026
Viewed by 128
Abstract
As global food security challenges intensify, edible crickets are recognized as sustainable protein alternatives; however, genomic resources for commercially important species remain limited, restricting evolutionary inference and the development of robust tools for farm management. We sequenced and assembled the complete mitochondrial genomes [...] Read more.
As global food security challenges intensify, edible crickets are recognized as sustainable protein alternatives; however, genomic resources for commercially important species remain limited, restricting evolutionary inference and the development of robust tools for farm management. We sequenced and assembled the complete mitochondrial genomes of Gryllus bimaculatus and provided the first report for Teleogryllus mitratus, both derived from commercial farms in Thailand, using high-throughput Illumina sequencing, achieving high coverage depths of 32,391× and 63,258×, respectively. The circular mitochondrial genomes were 15,955 bp and 16,046 bp and exhibited the typical insect mitochondrial gene complement of 37 genes, with a strong AT bias. Selective pressure analyses indicated pervasive purifying selection across all protein-coding genes (PCGs) (ω < 1), while episodic diversifying selection was detected in cox1, cox3, cytb, and nad5; additionally, atp8 displayed a comparatively elevated ω. Codon usage analyses revealed a strong preference for AT-ending codons, with leucine codons showing the highest bias. Phylogenetic analyses using concatenated protein-coding and ribosomal RNA genes recovered well-supported relationships within Gryllidae. These farm-derived mitogenomes provide practical foundations for molecular species authentication, population monitoring, and comparative analyses relevant to breeding and traceability. Furthermore, they provide candidate loci for future investigations into mitochondrial evolutionary dynamics and the potential development of molecular markers for commercial breeding management. Full article
(This article belongs to the Section Animal Genetics and Genomics)
14 pages, 1877 KB  
Article
Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and COL2A1 Gene Variant
by Akvile Bruzaite, Alvita Vilkeviciute-Petraite, Dzastina Cebatoriene, Dalia Zaliuniene, Ieva Ciapiene, Alina Smalinskiene, Loresa Kriauciuniene and Rasa Liutkeviciene
Int. J. Mol. Sci. 2026, 27(8), 3697; https://doi.org/10.3390/ijms27083697 - 21 Apr 2026
Viewed by 223
Abstract
Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the COL2A1 [...] Read more.
Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the COL2A1 rs1635529 polymorphism and AMD, as well as its relation to specific metabolites. The study comprised 919 participants: 261 with early AMD, 229 with exudative AMD, and 429 controls. DNA was extracted using the salting-out method, and genotyping was performed using real-time PCR. Metabolite levels were analysed with liquid chromatography–mass spectrometry. Statistical analysis was conducted using IBM SPSS Statistics 27.0. Logistic regression revealed that carriers of the GT + TT genotypes had a 1.63-fold higher risk of early AMD (p = 0.046). The T allele was also linked to a 1.67-fold elevated risk (p = 0.033). No significant associations were observed in exudative AMD. Furthermore, lower leucine levels were noted in exudative AMD patients, and inosine levels were reduced in GT genotype carriers within the early AMD group. The COL2A1 rs1635529 polymorphism showed a nominal association with early AMD, but not exudative AMD. Differences in leucine and inosine levels were observed, suggesting a potential link between genetic variation and metabolic alterations. These findings indicate possible involvement of collagen-related and metabolic pathways in early disease development; however, the results should be interpreted with caution and require validation in larger studies. Full article
(This article belongs to the Section Molecular Biology)
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19 pages, 1841 KB  
Article
Initial Soil Organic Carbon Level Governs Contrasting Carbon Responses to Fresh-Straw Input in Long-Term Straw-Returned Soils
by Yonghua Li, Xidan Zhang, Jiaqiao Luo and Peng Ning
Agronomy 2026, 16(8), 838; https://doi.org/10.3390/agronomy16080838 - 21 Apr 2026
Viewed by 230
Abstract
Soil organic carbon (SOC) responses to straw return are strongly influenced by active carbon dynamics and extracellular enzyme responses, yet how these processes vary with initial SOC status and long-term straw-return history remains unclear. To address this question, we conducted a controlled incubation [...] Read more.
Soil organic carbon (SOC) responses to straw return are strongly influenced by active carbon dynamics and extracellular enzyme responses, yet how these processes vary with initial SOC status and long-term straw-return history remains unclear. To address this question, we conducted a controlled incubation experiment using soils from long-term straw removal (CK) and straw return (SR) plots at two sites with contrasting SOC levels: a carbon-poor fluvo-aquic soil in Quzhou (QZ) and a carbon-rich black soil in Gongzhuling (GZL). Three fresh-straw input levels were imposed, and CO2 release, SOC, labile C and N pools, extracellular enzyme activities, and ecoenzymatic stoichiometry were determined. Fresh-straw input markedly stimulated carbon mineralization in both soils, but SOC responses differed substantially. In QZ, SOC increased 12.1–15.7% at day 7 (vs. T0) and remained 6.7–12.1% above the control at day 90 under the long-term straw-return background. In contrast, GZL showed only minor early SOC responses, and doubled straw input reduced SOC 4.9–9.5% at day 90 despite a stronger dissolved organic carbon (DOC) pulse and greater cumulative CO2 release. Enzyme responses also differed between soils: higher straw input in QZ enhanced β-cellobiohydrolase (CBH), β-xylosidase (BX), and especially L-leucine aminopeptidase (LAP), accompanied by lower ecoenzymatic C:P and higher vector angle, whereas GZL showed later activation of CBH, BX, and NAG with only slight changes in vector angle. Overall, our results indicate that initial SOC status and long-term straw-return history jointly regulate whether fresh-straw input promotes net SOC accumulation or enhanced mineralization. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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18 pages, 1819 KB  
Article
Comparative Phytochemical Profiling and Antioxidant Activity of Pigeon Pea (Cajanus cajan (L.) Huth) During Seed Germination and Hydroponic Cultivation
by Sumalee Chookhampaeng, Torphan Bubphachuen, Teeraporn Katisart, Nonthiwat Taesuk, Chanakran Papayrata, Sukanya Nonthalee and Suthira Maneechai
Diversity 2026, 18(4), 234; https://doi.org/10.3390/d18040234 - 19 Apr 2026
Viewed by 266
Abstract
Cajanus cajan (L.) Huth (Fabaceae) is a food legume of considerable nutritional and functional significance. This study examined the comparative effects of salt stress on seed germination, hydroponic growth, and phytochemical accumulation across two developmental stages: 10-day-old germinated seeds and 45-day-old hydroponically grown [...] Read more.
Cajanus cajan (L.) Huth (Fabaceae) is a food legume of considerable nutritional and functional significance. This study examined the comparative effects of salt stress on seed germination, hydroponic growth, and phytochemical accumulation across two developmental stages: 10-day-old germinated seeds and 45-day-old hydroponically grown plants, using NaCl solutions at concentrations of 0, 25, 50, 75, 100, and 150 mM. Both germination rate and growth were greatest at 0–25 mM NaCl, with performance declining at higher concentrations. LC–MS/MS analysis of free amino acids in 10-day-germinated seeds revealed a salt-induced metabolic shift. Proline, leucine, and phenylalanine were the dominant free amino acids and increased progressively with rising NaCl concentrations. Phytochemical profiling by HPLC identified gallic acid, catechin, and genistin as the major compounds, with increased levels under salinity stress. Germinated seeds at 150 mM NaCl, germinated seeds exhibited the highest phytochemical accumulation, with total phenolic content (TPC), total flavonoid content (TFC), and DPPH activity reaching 18.192 ± 0.020 mg GAE/g extract, 8.519 ± 0.026 mg QE/g extract, and 11.623 ± 0.284 mg AAE/g extract, respectively. Phytochemical responses in 45-day hydroponic plants varied by tissue type. Leaves exhibited declining TPC and TFC with increasing NaCl (from 29 to 16 mg GAE/g and 41 mg QE/g extract), while stems showed the opposite trend, reaching 18 mg GAE/g and 21 mg QE/g extract at 50 mM. Root tissues maintained comparatively low phytochemical levels throughout. Notably, DPPH scavenging capacity increased across all tissues under salt stress, with peak values of 12–13 µg AAE/g extract recorded at 50 mM NaCl. These results indicate that salt stress exerts stage- and organ-dependent effects on phytochemical accumulation in C. cajan. High salinity during germination stimulates bioactive compound production, whereas moderate salinity appears to be the threshold at which antioxidant capacity is maximized in hydroponic systems. These observations point to the practical utility of controlled salt elicitation as a strategy for enriching pigeon pea with health-promoting phytochemicals, reinforcing its potential as a functional food crop. Full article
(This article belongs to the Special Issue Ethnobotany and Plant Diversity: Conservation and Sustainable Use)
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17 pages, 9284 KB  
Article
Synergistic Effects of Multi-Kinase Inhibition on LRRK2-G2019S and Alpha-Synuclein Pathologies in Models of Parkinson’s Disease
by Xiaoguang Liu, Sean Baxely, Michaeline L. Hebron and Charbel Moussa
Biomedicines 2026, 14(4), 927; https://doi.org/10.3390/biomedicines14040927 - 18 Apr 2026
Viewed by 269
Abstract
Introduction: Pathogenic mutations in leucine-rich repeat protein kinase-2 (LRRK2), particularly G2019S, constitute the most common cause of autosomal dominant PD. Methods: Mouse models encoding human mutant alpha-synuclein (SNCA A53T) and LRRK2 G2019S were treated with a brain-penetrant [...] Read more.
Introduction: Pathogenic mutations in leucine-rich repeat protein kinase-2 (LRRK2), particularly G2019S, constitute the most common cause of autosomal dominant PD. Methods: Mouse models encoding human mutant alpha-synuclein (SNCA A53T) and LRRK2 G2019S were treated with a brain-penetrant kinase inhibitor (BK40196). Behavior, nigrostriatal and mesolimbic dopamine (DA) pathways were examined. Results: Mice harboring LRRK2 G2019S do not show age-dependent motor symptoms, but mice encoding SNCA A53T display motor deficits, while both strains exhibit anxiety-like behavior and BK40196 improves motor and behavioral defects. BK40196, a multi-kinase inhibitor of Abelson (Abl), Discoidin domain receptor (DDR)-1, c-KIT and FYN, alters microglial morphology and alpha-synuclein levels in SNCA A53T mice and improves DA neurotransmission, primarily via the nigrostriatal system. BK40196 inhibits brain LRRK2 G2019S (IC50 of 89nM) and does not affect phosphorylated or total peripheral LRRK2 levels (lungs, kidneys, liver, etc.). LRRK2 G2019S mice treated with BK40196 exhibit distinct increases in DA in mesolimbic neurons such as the nucleus accumbens (NAcc), suggesting differential mechanisms of DA neurotransmission in mutant alpha-synuclein and LRRK2 models of PD. Conclusions: LRRK2 G2019S may primarily involve mesolimbic pathways leading to nonmotor symptoms independent of the motor and behavioral manifestations associated with alpha-synuclein via the nigrostriatal system. BK40196 may provide a comprehensive and synergistic therapeutic approach that addresses multiple mechanisms to reduce the pathologies related to LRRK2 G2019S and/or SNCA in PD. The multiple pathologies of PD necessitate a holistic approach that simultaneously targets inflammation and autophagy and LRRK2 inhibition. Full article
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27 pages, 2780 KB  
Article
Identification and Integration of LRG1-Induced Differentially Expressed Gene (DEG) Hub Profiles in Breast Cancer Cells
by Federico Osorio-Antonio, Daniela Michel Diaz-González, Gabriela Elizabeth Campos-Viguri, José Manuel Sánchez-López, José Luis Cortez-Sánchez, Francisco Castelán, Jesús Ramses Chávez-Rios, Paola Maycotte-González, Paulina Cortés-Hernández, Oscar Peralta-Zaragoza and Elizabeth Bautista-Rodríguez
Int. J. Mol. Sci. 2026, 27(8), 3613; https://doi.org/10.3390/ijms27083613 - 18 Apr 2026
Viewed by 348
Abstract
Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast [...] Read more.
Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast cancer are poorly defined. We evaluated the effects of recombinant human LRG1 (rhLRG1) on cell viability and migration in MDA-MB-231 TNBC cells and performed transcriptomic profiling followed by functional enrichment analyses using GenArise, Cytoscape, and R-based tools. RhLRG1 treatment significantly increased cell viability and migration. Transcriptomic analysis revealed activation of key oncogenic cascades, including the PI3K/AKT, MAPK, and RAS signaling pathways. Hub-gene analysis identified upregulated genes involved in proliferation (NRAS, STAT5B, IGF2), angiogenesis (PGF, ANGPT2), and apoptosis (CASP8, BAD), whereas downregulated genes were associated with apoptotic resistance (BCL2, MCL1) and adhesion (LAMB1, ITGB4). Functional enrichment highlighted LRG1’s role in the bioinformatic analysis of differentially expressed genes that were obtained from microarray assays. LRG1 remodels the tumor microenvironment by promoting proliferation, angiogenesis, and apoptotic sensitivity while repressing resistance-related genes. These findings position LRG1 as a potential diagnostic biomarker and therapeutic target for advanced breast carcinoma. Full article
(This article belongs to the Section Molecular Oncology)
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21 pages, 3484 KB  
Article
Design of Dipeptite-Based Organogelators as Separators of Cationic Dye Cyristal Violet from Water
by Gülşen Kaya, Mehmet Çolak, Halil Hoşgören and Necmettin Pirinccioglu
Gels 2026, 12(4), 337; https://doi.org/10.3390/gels12040337 - 17 Apr 2026
Viewed by 274
Abstract
The development of new advanced functional materials from low-molecular-weight gelators and their new potential applications have occupied a considerable place in research. The present study involves the design of dipeptide-based organogelators with enhanced hydrogen bonding network potentials and phase-selective capacities, possessing a minimum [...] Read more.
The development of new advanced functional materials from low-molecular-weight gelators and their new potential applications have occupied a considerable place in research. The present study involves the design of dipeptide-based organogelators with enhanced hydrogen bonding network potentials and phase-selective capacities, possessing a minimum gelation concentration of 0.2–0.4% w/v in different fluids. Seven new dipeptide organogelators were prepared based on a one-step reaction from two-component salt forms, the combination of Nε-alkanoyl-L-lysine ethyl ester with N-alkanoyl-L-amino acids (L-alanine, L-leucine, and L-phenylalanine), with high yields of up to 90. All the gel materials were extremely stable at room temperature, having a shelf life of several months, and formed gels in pharmaceutical fluids such as ethyl palmitate, ethyl myristate, and ethyl laurate, 1,2-propanediol, and liquid paraffin (oils widely used in pharmaceutical formulations), which meet the criteria of biological materials delivery. Their gelation properties were evaluated by rheological measurements. A very significant breakthrough in the current study is that organogels remove the toxic dye, crystal violet (CV), from water in a phase-selective manner with an extremely low gelator concentration. The dye and gelators are successively recovered via ethanol precipitation after the completion of the phase extraction process. Molecular dynamic calculations provide evidence for the 3D structures of the gels. Full article
(This article belongs to the Section Gel Chemistry and Physics)
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26 pages, 2855 KB  
Article
FcLRR1 Regulates Hyphal Growth and Plant Infection in Fusarium circinatum
by Tingting Dai, Chao Chen, Fangyi Ju, Jiahui Zang, Zhongqiang Qi, Haiwen Wang, Xiaorui Zhang and Chun Yang
J. Fungi 2026, 12(4), 282; https://doi.org/10.3390/jof12040282 - 16 Apr 2026
Viewed by 298
Abstract
Pitch canker caused by the fungus Fusarium circinatum is a destructive disease that affects pines in Europe, South Africa, and North America, particularly along the southeastern and western coasts of the United States. This study systematically elucidated the function of the Leucine-rich repeat [...] Read more.
Pitch canker caused by the fungus Fusarium circinatum is a destructive disease that affects pines in Europe, South Africa, and North America, particularly along the southeastern and western coasts of the United States. This study systematically elucidated the function of the Leucine-rich repeat (LRR) protein FcLRR1 in the pine pitch canker pathogen Fusarium circinatum. A total of 13 LRR proteins were identified via bioinformatic analysis. Using a gene knockout system, we demonstrated that deletion of FcLRR1 significantly impaired vegetative growth, conidiation, and conidium germination; led to a complete loss of macroconidia production; and drastically reduced abiotic stress tolerance and virulence. Transcriptome profiling revealed 612 downregulated genes, which were significantly enriched in pathways such as starch and sucrose metabolism, indicating that FcLRR1 modulated energy supply and pathogenicity through carbon source utilization. Through genome-wide protein structure modeling and yeast two-hybrid assays, we identified and validated the interaction between FcLRR1 and ALG-11, among other candidate proteins, further supporting its involvement in carbon metabolism, cell wall integrity, and pathogenesis. This study represents the first functional characterization of an LRR-containing protein in a forest pathogenic fungus and provides a foundational basis for developing targeted disease control strategies. Full article
(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)
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32 pages, 5815 KB  
Review
Molecular Parallels: Innate Immunity and Pathogen Strategies in Plants and Animals
by Lesly Cristel Jiménez Cabrera, Pablo Alejandro Gamas-Trujillo, César De los Santos-Briones, Luis Sáenz-Carbonell, Ignacio Islas-Flores, Karla Gisel Carreón-Anguiano, Roberto Vázquez-Euan, Nuvia Kantún-Moreno and Blondy Canto-Canché
Immuno 2026, 6(2), 27; https://doi.org/10.3390/immuno6020027 - 15 Apr 2026
Viewed by 476
Abstract
Both plants and animals have developed a sophisticated two-tiered innate immune system. This involves an initial recognition of microbial patterns conserved on the cell surface (PAMP-triggered immunity) and a subsequent more specific intracellular recognition of pathogenic effectors or their activities (effector-triggered immunity). A [...] Read more.
Both plants and animals have developed a sophisticated two-tiered innate immune system. This involves an initial recognition of microbial patterns conserved on the cell surface (PAMP-triggered immunity) and a subsequent more specific intracellular recognition of pathogenic effectors or their activities (effector-triggered immunity). A common fundamental feature is the use of NLR-like intracellular receptors to detect insider threats. Both plant NLRs (receptors containing nucleotide-binding domains and leucine-rich repeats) and animal NLRs (NOD-like receptors) share a modular tripartite architecture, typically featuring a central nucleotide-binding domain (NBD/NOD) and C-terminal leucine-rich repeats (LRRs). The NBD/NOD is crucial for facilitating the exchange of ADP/ATP, acting as a molecular switch to promote oligomerization and activation of NLRs in both kingdoms. In this review, we summarize the similarities and differences between plant and animal molecular perception and immunity mechanisms. Additionally, we highlight the fact that some human pathogens can infect plants, and crucially, some plant pathogens are capable of causing disease in humans. This suggests conserved molecular strategies to invade and manipulate host cells belonging to different biological kingdoms, uncovering that plant and human pathology may benefit from future investigations in their respective fields. Full article
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16 pages, 1550 KB  
Review
Leucine-Rich Repeat Kinase 2 (LRRK2) in Glucose Metabolism and Metabolic–Neuroinflammatory Crosstalk
by Fumitaka Kawakami, Motoki Imai, Masanori Ogata, Toshiya Habata, Shun Tamaki, Rei Kawashima, Yoshifumi Kurosaki, Sayaka Miyai, Moragot Chatatikun, May Pyone Kyaw and Kenichi Ohba
Biomolecules 2026, 16(4), 588; https://doi.org/10.3390/biom16040588 - 15 Apr 2026
Viewed by 287
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a multidomain serine/threonine kinase and a major genetic contributor to Parkinson’s disease (PD). Although LRRK2 has been extensively studied in neurodegeneration, emerging evidence indicates that it also plays a critical role in systemic metabolism. LRRK2 regulates glucose [...] Read more.
Leucine-rich repeat kinase 2 (LRRK2) is a multidomain serine/threonine kinase and a major genetic contributor to Parkinson’s disease (PD). Although LRRK2 has been extensively studied in neurodegeneration, emerging evidence indicates that it also plays a critical role in systemic metabolism. LRRK2 regulates glucose homeostasis through modulation of insulin signaling, vesicle trafficking, mitochondrial function, and inflammatory responses. Studies using LRRK2 knockout and knock-in models, including the pathogenic G2019S mutation, have revealed abnormalities in insulin sensitivity, adipose tissue inflammation, hepatic glucose production, and skeletal muscle metabolism. Mechanistically, LRRK2 phosphorylates Rab GTPases, thereby controlling insulin receptor trafficking and GLUT4 translocation. In addition, LRRK2 influences mitochondrial dynamics and reactive oxygen species production, linking metabolic stress to inflammatory signaling. Importantly, LRRK2 also regulates innate immune pathways, including TLR4–NFκB signaling and inflammasome activation, thereby connecting peripheral metabolic dysfunction to neuroinflammation. Here, we propose an integrated metabolic–neuroinflammatory crosstalk model in which LRRK2 functions as a molecular coordinator linking peripheral metabolic dysfunction to central neurodegeneration. In this framework, systemic metabolic stress—characterized by insulin resistance, chronic inflammation, advanced glycation end product (AGE) accumulation, and blood–brain barrier disruption—drives microglial activation and neurodegenerative processes. Understanding this systemic axis may provide new therapeutic opportunities targeting both metabolic dysfunction and neurodegeneration in PD. Full article
(This article belongs to the Section Cellular Biochemistry)
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16 pages, 2768 KB  
Article
Metabolomic Profiling of Intestinal Contents in Rice Paddy-Cultured Eriocheir sinensis: Linking Gut Microbiota Composition with Metabolic Pathway Dynamics
by Jinpeng Zhang, Yayu Wang, Yunxiao Yang, Hong Lin, Yuhong Yang and Dayan Hu
Fishes 2026, 11(4), 228; https://doi.org/10.3390/fishes11040228 - 14 Apr 2026
Viewed by 239
Abstract
Rice–crab coculture, as China’s third-largest integrated farming model, is pivotal for sustainable Chinese mitten crab aquaculture. This study conducted untargeted metabolomics and 16S rRNA gene sequencing on gut contents of crabs from rice fields and ponds, integrating metabolic and microbial profiles. We aimed [...] Read more.
Rice–crab coculture, as China’s third-largest integrated farming model, is pivotal for sustainable Chinese mitten crab aquaculture. This study conducted untargeted metabolomics and 16S rRNA gene sequencing on gut contents of crabs from rice fields and ponds, integrating metabolic and microbial profiles. We aimed to reveal the chemical traits of rice-field Chinese mitten crab linked to gut microbiota, providing scientific guidance for optimizing culture practices and developing microbial additives. Both groups were dominated by the phyla Firmicutes, Proteobacteria, and Bacteroidota, but the phylum Bdellovibrionota was not detected in group R. A total of 1271 distinct amplicon sequence variants (ASVs) were identified, which were annotated to 649 genera. At the ASV level, the Chao1 index for the R group (197.12 ± 17.88) was notably lower compared to the P group (288.75 ± 30.59) (p < 0.01). In contrast, the Shannon index for the R group (3.90 ± 0.06) was significantly greater than that of the P group (3.70 ± 0.06) (p < 0.01). The PCA plot demonstrated a distinct discrimination between the groups. The P group had more microbial species but was dominated by Candidatus_Bacilloplasma, resulting in uneven distribution. In contrast, the R group had fewer species but a more balanced distribution. Among 3531 metabolites identified in both groups, 865 differed significantly. Compared to P, 736 metabolites were significantly upregulated and 129 were significantly downregulated in R. Key metabolic pathways included amino acid, carbohydrate, cofactor and vitamin metabolism, signaling, and xenobiotics biodegradation. Group R had higher levels of L-leucine, L-phenylalanine, L-tyrosine, 2-amino-1-phenylethanol, choline, and pyrophaeophorbide a, which correlated with genera like Candidatus_Hepatoplasma and Aeromonas (p < 0.05), suggesting better nutritional value, flavor, and metabolic health in rice-field crabs. Full article
(This article belongs to the Section Aquatic Invertebrates)
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23 pages, 32795 KB  
Article
Genome-Wide Identification and Expression Profiling of HD-Zip Family Genes in Flax (Linum usitatissimum L.)
by Yamin Niu, Yanni Qi, Limin Wang, Wenjuan Li, Zhao Dang, Yaping Xie, Wei Zhao, Gang Wang, Zuyu Hu, Nan Lu, Xiaoyan Zhu, Jing Zheng, Junyan Wu and Jianping Zhang
Curr. Issues Mol. Biol. 2026, 48(4), 402; https://doi.org/10.3390/cimb48040402 - 14 Apr 2026
Viewed by 205
Abstract
The homeodomain-leucine zipper (HD-Zip) transcription factor family is conserved in land plants and is critical for regulating growth, development, and stress responses. Flax (Linum usitatissimum L.) is an economically valuable dual-purpose crop valued for its high nutrition and notable drought tolerance; however, [...] Read more.
The homeodomain-leucine zipper (HD-Zip) transcription factor family is conserved in land plants and is critical for regulating growth, development, and stress responses. Flax (Linum usitatissimum L.) is an economically valuable dual-purpose crop valued for its high nutrition and notable drought tolerance; however, its HD-Zip gene family has not been systematically characterized. In this study, a comprehensive genome-wide analysis was performed to identify and characterize the HD-Zip family in flax. A total of 34 LuHD-Zip genes were identified, which were unevenly distributed across 15 chromosomes and exhibited substantial variation in physicochemical properties. The encoded proteins ranged from 200 to 372 amino acids in length, with molecular weights of 22.7–40.3 kDa and theoretical isoelectric points (pI) of 4.49–9.46. All LuHD-Zip proteins were predicted to be hydrophilic and localized to the nucleus. Phylogenetic analysis divided these proteins into two major subfamilies (Group 1 and Group 2), a classification strongly supported by conserved gene structures and motif compositions, implying potential functional redundancy within each group. Gene duplication analysis revealed that segmental duplication events (29 pairs) were the primary drivers of family expansion. Comparative syntenic analysis further indicated that the LuHD-Zip gene family has remained relatively conserved throughout evolution. Promoter cis-element analysis identified multiple regulatory elements associated with hormone signaling and abiotic stress responses, suggesting complex transcriptional control in response to environmental stimuli. Expression profiling via quantitative real-time PCR (qRT-PCR) demonstrated that LuHD-Zip genes exhibit tissue-specific expression patterns and are differentially regulated by various phytohormone treatments and abiotic stresses. This study provides the first genome-wide characterization of the HD-Zip gene family in flax, offering valuable insights into its evolution and potential functions. These findings establish a solid foundation for future functional investigations of the LuHD-Zip gene family. Full article
(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants—3rd Edition)
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Article
Effects of Probiotic Supplementation on Gut Microbiota and Fecal Metabolome in Autism Spectrum Disorders: A Secondary Analysis of a Randomized Clinical Trial in Preschoolers
by Letizia Guiducci, Luca Laghi, Nicolò Dellarosa, Paola Mastromarino, Margherita Prosperi, Filippo Muratori and Sara Calderoni
Metabolites 2026, 16(4), 262; https://doi.org/10.3390/metabo16040262 - 13 Apr 2026
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Abstract
Background/Objectives: Recently, a randomized clinical trial evaluated whether a six-month probiotic administration could reduce symptom severity in preschool children with Autism Spectrum Disorders (ASD), with (GI) or without (NGI) gastrointestinal symptoms. Significant positive changes were observed only in NGI children. A second explorative [...] Read more.
Background/Objectives: Recently, a randomized clinical trial evaluated whether a six-month probiotic administration could reduce symptom severity in preschool children with Autism Spectrum Disorders (ASD), with (GI) or without (NGI) gastrointestinal symptoms. Significant positive changes were observed only in NGI children. A second explorative study on children prior to intervention identified a fecal metabolome fingerprint associated with ASD severity. Building on these findings, the present study aimed to assess whether metabolomics could monitor changes in ASD severity following probiotic administration using a subset of samples from the same trial. Second, this study aimed to identify fecal metabolites to be monitored in children to predict whether their autism severity may decrease after probiotic or placebo treatment. Methods: Evaluations of the fecal metabolome and microbiota could be completed on 57 children before and after a double-blind administration of a probiotic mixture or a placebo. Results: In NGI children the probiotic was found to influence the concentration of the amino acids aspartate, leucine, tryptophan, and valine, together with nicotinate and the short chain fatty acids acetate, butyrate, isobutyrate, and propionate. Lactobacilli and Sutterella showed significant changes in response to probiotic administration (p < 0.05). Acetate, 4-hydroxyphenyl, galactose, proline, and tyramine were identified as key fecal metabolites for prediction purposes. Conclusions: The present exploratory analysis, despite the small sample size, suggests that fecal metabolomics may provide a useful approach for monitoring and potentially for predicting changes in ASD severity following probiotics administration. Full article
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