The intestinal barrier plays a critical role in maintaining gastrointestinal health and nutrient utilization in yaks. This study investigated the effects of dietary RPG level and RPT supplementation on colonic barrier function and microbial composition in yaks. Twenty-eight healthy male yaks (3 years old; 192.7 ± 4.52 kg) were assigned to a 2 × 2 factorial design with two dietary rumen-protected glucose (RPG) levels (1.0% or 3.0% of dietary DM) and two rumen-protected taurine (RPT) supplementation levels (5 or 20 g/animal/day) for 63 days. High-level RPG impaired colonic physical barrier function by reducing tight junction protein expression and microbial diversity, whereas high-level RPT mainly compromised chemical and immune barrier function by decreasing diamine oxidase activity, mucin-2, and secretory immunoglobulin A, accompanied by alterations in the colonic microbial community. Significant interactions between RPG and RPT were observed for several barrier- and microbiota-related indices. Overall, the effects of RPG and RPT on colonic health were dose-dependent, and moderate supplementation, particularly the combination of 1.0% dietary RPG and 5 g/day RPT, was the most effective in maintaining colonic barrier integrity and microbial homeostasis in yaks.
Vip3 proteins secreted by the entomopathogenic bacterium Bacillus thuringiensis (Bt) have an important role in biological control against economically important lepidopteran pests. The elucidation of Vip3 protein structures has helped to address the roles of domains and amino acid positions involved in toxicity, especially in the N-terminal domains I and II, thereby supporting their more efficient utilization. In this study, we evaluated the impact of combinations of critical amino acid substitutions, selected from previous studies, in domains IV and V of the Vip3Aa90 protein on its insecticidal activity against three lepidopteran pests. The double mutant S543N/I544L, triple mutants S543N/I544L/E627A and S543N/I544L/S686R, and quadruple mutant S543N/I544L/E627A/S686R were constructed in Escherichia coli by site-directed mutagenesis. Among these, only the Vip3Aa mutant proteins S543N/I544L/E627A and S543N/I544L/E627A/S686R could be expressed and purified for bioassays. Both mutant proteins had similar toxicity against Spodoptera littoralis, showing higher insecticidal activity than the wild-type (WT) Vip3Aa90 at the LC90 level. However, at the LC50 level, only a slight improvement in toxicity was observed for the quadruple mutant. In the case of S. exigua, no significant difference in toxicity was observed for either of the two mutant proteins with respect to the WT at either LC level. Interestingly, for G. molesta, though the toxicity of the triple mutant did not differ significantly compared to that of the WT protein, that of the quadruple mutant showed a marked decrease in toxicity of over 10-fold. This study revealed that combining selected amino acid substitutions in domains IV and V can enhance Vip3Aa90 toxicity against some lepidopteran species but can be either neutral or even deleterious in others.
Coconut is an important livelihood and industrial crop for coastal communities in Thailand; however, limited information is available on the phenotypic diversity of traditional aromatic coconut populations cultivated by smallholders in southern Thailand. An on-farm survey was conducted in Phang Nga, Trang, Krabi, and Nakhon Si Thammarat, evaluating 27 palms representing nine populations (three palms per population) for 28 quantitative morphological, reproductive, fruit, yield, and coconut-water quality traits. A hierarchical linear mixed model, with province treated as a fixed effect and populations nested within province, was used to characterize phenotypic variation and obtain adjusted population-level BLUPs. Substantial phenotypic variation was observed among the surveyed populations. Var7 in Krabi recorded the highest fruit weight (2039 g) and kernel thickness; Var6 in Trang had the highest number of fruits per bunch (13.3); Var2 in Phang Nga had the highest water volume (430 mL); and Var9 in Nakhon Si Thammarat had the highest number of female flowers (20). Principal component analysis showed that the first five components explained 72.6% of the total phenotypic variation, with fruit, reproductive, water, and vegetative traits contributing strongly to population differentiation. Correlation network analysis further identified coordinated associations among vegetative vigor, leaf morphology, and fruit and yield traits. The study provides a baseline phenotypic characterization of Nam Hom coconut populations under smallholder conditions and identifies population–province combinations with promising trait profiles for further evaluation.
Panax ginseng (Panax ginseng C.A. Mey.) produces pharmacologically valuable ginsenosides. WD40-repeat (WDR) proteins act as versatile regulators of plant specialized metabolism, yet their biological roles under methyl jasmonate (MeJA) elicitation remain largely uncharacterized in ginseng. In this study, we identified 29 PgWDR family members at the whole-genome level, and systematically analyzed their phylogeny, gene structure, cis-acting promoter elements, as well as organ- and development-dependent expression patterns. Six candidate genes potentially associated with ginsenoside biosynthesis were screened through integrating gene–metabolite correlation analysis and gene co-expression analysis. Under MeJA treatment, three of these candidates showed statistically significant expression responses, while the other three exhibited variable expression fluctuations with no statistical significance. PgWDR24 displayed a positive correlation with key ginsenoside biosynthetic enzyme genes, and a negative correlation with protopanaxadiol-type ginsenoside accumulation. Combined with its predicted nuclear localization, we hypothesize that PgWDR24 participates in the negative modulation of protopanaxadiol-type ginsenoside accumulation, although further genetic functional validation is still required. This work provides valuable candidate genes for deciphering ginsenoside regulatory networks and offers support for molecular-assisted breeding of high-quality ginseng.
Rice cultivation is an important source of GHG emissions, particularly CH4 and N2O, which are strongly influenced by water and N management. However, the relationship between GHG emissions and stem aerenchyma development among rice varieties remains poorly understood. This study evaluated CH4 and N2O emissions and stem aerenchyma development in two rice varieties, PTT1 and KDML105, cultivated under flooded and non-flooded conditions with two N regimes (0 and 120 kg ha−1). GHG fluxes were measured at three growth stages: before maximum tillering, panicle initiation, and flowering, while stem aerenchyma was assessed at the early heading stage. The results showed that water conditions and N fertilizer significantly affected cumulative CH4 emissions, whereas there was no significant effect of rice variety. Applying both water and N also increased GWP and GHGI in rice cultivation, with little difference between the rice varieties. Notably, stem aerenchyma development was not significantly associated with GHG transport under different conditions. These findings demonstrate that water and N management affected rice physiological responses, but stem aerenchyma development alone may not be associated with GHG transport under specific environmental conditions. These results provide valuable guidance for optimizing water and N management in rice production systems to maintain crop productivity while reducing environmental impacts.
The ‘miracle tree’ Moringa oleifera from the Moringaceae family is recognized for its rich nutritional value and therapeutic properties. This study aimed to evaluate the phytopharmaceutical compound Moringa isothiocyanate-1 (MIC-1) isolated from hydroalcoholic extract of M. oleifera seeds for the treatment of seizures and anxiety in adult zebrafish. MIC-1 (up to 0.5 mg/mL) did not show any acute toxic effects over a 96-h period. Moreover, MIC-1 (0.005 and 0.05 mg/mL) delayed the onset of seizures induced by pentylenetetrazol, indicating anticonvulsant activity. The anticonvulsant effects of MIC-1 (0.05 mg/mL) were reversed by flumazenil, suggesting a mechanism involving the GABAA receptor. Furthermore, MIC-1 (0.05 mg/mL) has anxiolytic effects, with involvement of the serotonergic and GABAergic systems. In silico assays confirmed the interaction of MIC-1 with the GABAA, 5-HT1B, 5-HT2A/C, and 5-HT3A/B receptors. Additionally, MIC-1 was effective in treating anxiety related to alcohol withdrawal in zebrafish. These findings suggest the pharmacological potential of MIC-1 for the development of new treatments for seizures and anxiety.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by neuroinflammation and demyelination. Although treatment options for MS have increased over the past decade, current therapies primarily target the peripheral immune system and are often associated with significant side effects. Moreover, these therapies still do not offer solutions for the resulting neurodegeneration that accompanies the progression of the disease. Findings from research using cellular and animal models and studies in humans highlight the neuroprotective and anti-inflammatory properties of apigenin, a flavonoid present in several commonly consumed plant species, such as cabbage, orange, tea, onion, and chamomile. This review compiles chemical and current evidence on the therapeutic potential of apigenin, primarily on its ability to modulate neuroinflammation and underscore the need for further investigation into its clinical applications as an adjuvant therapy for MS.
Objective: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. Methods: Thirty-six Sprague–Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson’s trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF−α interleukin-1β IL−1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson–Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of −14.74, −14.92, −17.58, −23.04, and −16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. Conclusions: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.
Tobamoviruses (viruses in the genus Tobamovirus, family Virgaviridae) lead to major yield losses in economically important crops around the world. In this review, we go beyond the canonical gene expression framework by integrating recent discoveries of reverse open reading frames (rORFs) on the negative-strand RNA. These rORFs have only been experimentally validated in cucumber green mottle mosaic virus (CGMMV), with predicted sequence-conserved homologs across a subset of the genus, including TMV, ToBRFV, and PMMoV. However, they are not universally present in all tobamoviruses. We systematically dissect the infection cycle—from disassembly and replication to cell-to-cell and systemic movement—with an emphasis on the host factors hijacked at each stage. We synthesize current understanding of plant antiviral immunity, focusing on RNA silencing and NLR receptor-mediated resistance as two pillars of defense, along with the transcription factors and microRNAs that orchestrate these responses. We critically evaluate the experimental evidence for both plant defenses and viral counter-strategies, noting that many mechanistic models derive from limited model systems. We further characterize host genetic resistance and susceptibility factors applicable to crop breeding. These resources include dominant NLR and non-NLR resistance, as well as recessive resistance derived from modified host susceptibility genes. We address how viral mutations, recombination and fitness trade-offs undermine resistance durability. We then evaluate their practical deployment through conventional breeding, the exploitation of quantitative resistance, and genome editing, and outline associated agronomic drawbacks and regulatory constraints. Using ToBRFV as a case study, we analyze its epidemiological traits and assess the current arsenal of surveillance tools, from field diagnostics to remote sensing. Finally, we survey management strategies across a spectrum of maturity. Some approaches, including sanitation protocols and conventionally bred resistant cultivars, have proven effective under field conditions. The first dsRNA-based biopesticide has recently been registered in China, while other biological control agents and low-risk chemical approaches remain largely at the experimental stage. We also discuss the bottlenecks that impede lab-to-field transition and highlight promising solutions such as precision breeding and evolution-oriented cultivar deployment. By bridging molecular virology, epidemiology, and integrated disease management, this review provides a critical, bench-to-field framework for the sustainable control of tobamoviruses.
Marine bacteria represent a vast and largely untapped resource for biotechnological innovation, offering solutions to global challenges in health, sustainability, and environmental conservation. The ocean’s unique conditions have driven marine bacteria to evolve diverse metabolic capabilities, resulting in the production of bioactive compounds, enzymes, and other metabolites with wide-ranging applications. Recent advances in high-throughput sequencing, metagenomics, and analytical chemistry have unlocked new opportunities for leveraging these microorganisms in fields as varied as medicine, agriculture, and bioremediation. This review highlights the role of marine bacteria in the One Health framework, showcasing their contributions to antimicrobial discovery, nutraceutical development, pathogen biocontrol, and environmental cleanup, including microplastic degradation. This review also examines emerging methodologies such as microbiome mining and advanced culturing techniques, which hold the key to realizing the full potential of marine bacteria in a sustainable bioeconomy. By bridging fundamental research with applied sciences, marine biotechnology promises to deliver transformative impacts on human, animal, and environmental health.
Fungi play essential roles in ecosystems as pathogens, mutualists, and ubiquitous decomposers. However, like many important microbes, the spatial distribution of species and natural populations remains poorly understood compared to plants and animals. Many fungi are described as global generalists because they occur across wide geographic areas, but it remains unclear how and if these species are constrained by climate or geographic barriers. In this study, we used Species Distribution Models to infer the global climatic suitability of three common and globally distributed fungi: Aspergillus flavus, Penicillium chrysogenum and Aspergillus fumigatus. Models were constructed using global occurrence data from the Global Biodiversity Information Facility and were trained with Bioclimatic variables from the WorldClim dataset. All species’ models showed high prediction fit, with predicted occurrence concentrated in the temperate and subtropical regions and broadly structured patterns. Each species showed distinct predicted distributions, but they displayed considerable spatial overlap on a global scale. Together, these results demonstrate that even apparently globally occurring and generalist fungal species occupy climatically structured niches. This study highlights the utility of SDMs and it provides a framework for future studies integrating ecological, genomics and evolutionary perspectives among the difficult to assess geographically widespread and common fungi.
Sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) is an inducible NAD-consuming enzyme and execution factor in axon degeneration. Rapid ATP collapse after SARM1 activation, however, is not fully explained by NAD depletion alone. We used SARM1-overexpressing HEK293 cells and the cell-permeant activator CZ-48 to examine SARM1-induced non-apoptotic cell death, termed sarmoptosis. CZ-48 induced cell death that was suppressed by HSP90/70-annotated ATP-competitive compounds, especially geldanamycin and VER-155008 (VER), without reducing SARM1 abundance. VER preserved NAD and ATP during SARM1 activation but failed to rescue FK866-mediated NAD starvation, thereby distinguishing CZ-48/SARM1-driven cytotoxicity from generic NAD depletion. In cell-free assays, purified SARM1 reduced ATP levels; this effect was enhanced by SARM1’s activator NMN and attenuated by its pharmacological inhibitors, although the in vitro activity was modest and the reaction products remain to be identified. ATPase-related perturbations, including thapsigargin and bafilomycin A1, also protected cells from CZ-48-induced death, further supporting a central role for ATP collapse in sarmoptosis. iTRAQ proteomics, MitoSOX Red staining, and DiOC6(3) staining revealed that CZ-48 treatment was associated with mitochondrial and metabolic remodeling, mitochondrial ROS accumulation, and mitochondrial depolarization, all of which were mitigated by VER. Collectively, these findings support a convergent ATP-collapse model in which SARM1 activation promotes NAD depletion, directly consumes ATP, and is associated with mitochondrial dysfunction that may amplify ATP-production failure.
Marine cyanobacteria represent a promising but underexplored bioresource for rare earth element (REE) management. This study investigated the effects of lanthanum (La, 10 mg L−1) on four cyanobacterial strains isolated from Black Sea periphyton: Desertifilum tharense AqMaPh-IBSS-CYA-1, Toxifilum mysidocida AqMaPh-IBSS-CYA-10, Salileptolyngbya sp. IBSS-CYA-8, and Cyanobium sp. AqMaPh-IBSS-CYA-15. La induced a delayed hormetic response in Cyanobium sp. Under suboptimal light and temperature conditions, La supplementation supported 100% survival of all strains over 35 days, whereas controls perished. SEM-EDX indicated predominantly intracellular La localization, with surface-bound La detected only sporadically. ICP-MS revealed hyperaccumulation of La (9.5–13.3 mg g−1 dry weight, 110–226-fold enrichment) and co-accumulation of light REEs in filamentous strains. Strain-specific responses suggest distinct protection mechanisms: T. mysidocida may employ metal efflux and polyphosphate granule sequestration, suggesting potential for REE recovery; Salileptolyngbya sp. appears to show broad-spectrum metal binding, potentially useful for bioremediation; D. tharense seems to be the most sensitive under the tested conditions, suggesting potential as a REE bioindicator. These findings are preliminary, but they suggest that La may act not only as a toxicant but also as a metabolic modulator, highlighting the potential of these cyanobacteria as bioresources for sustainable REE management.
Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit.
To quantitatively characterize the pharmacokinetic and pharmacodynamic interactions between Hydroxysafflor Yellow A (HSYA) and Calycosin (CA) in cerebral ischemia–reperfusion injury (CIRI), a factorial experimental design was combined with a hierarchical coupled PK-PD modeling framework. The coupled PK model adequately described the concentration-time profiles of HSYA and CA under co-administration, with R2 values of 0.83 and 0.86, respectively, while the PK-PD model showed good fitting performance for Caspase-3 and HIF-1α, with all R2 values exceeding 0.97. Structural identifiability analysis showed that the newly introduced PK and PD coupling parameters were globally identifiable, and their Bootstrap 95% confidence intervals excluded zero. After Holm-Bonferroni correction, AUC0-t, AUC0-∞ and CL differed significantly between single and combined administration, whereas MRT did not. The model-derived relative contribution weights of HSYA and CA were quantified for both Caspase-3 and HIF-1α, with uncertainty assessed using Bootstrap 95% confidence intervals. Overall, the proposed coupled PK-PD framework provides a quantitative approach for characterizing component interactions and relative pharmacodynamic contributions in multi-component systems.
The LOR (LURP-one related) gene family encodes proteins containing conserved LOR domains; however, its functions in plant abiotic stress responses remain largely unexplored. In this study, we systematically identified and characterized the LOR gene family in the stress-tolerant wild tomato Solanum lycopersicoides using comprehensive bioinformatic analyses and conducted functional validation of the candidate gene ScLOR16. A total of 19 ScLOR members were identified and classified into eight phylogenetic subgroups. Numerous cis-acting elements associated with responses to abscisic acid (ABA), cold, and drought, including ABRE, LTR, and MBS, were detected in the promoter regions, suggesting that the ScLOR family may be broadly involved in ABA-mediated stress signaling pathways. RT-qPCR analysis revealed that ScLOR16 expression was significantly induced by both cold and drought treatments. Subcellular localization assays demonstrated that ScLOR16 is localized in both the nucleus and cytoplasm. Virus-induced gene silencing (VIGS) was subsequently employed to generate ScLOR16-silenced plants. Following 24 h of cold treatment at 4 °C and four days of drought stress, ScLOR16-silenced seedlings exhibited significantly less severe wilting symptoms than empty-vector controls. Physiological analyses showed that silenced plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activities, increased proline accumulation, and decreased thiobarbituric acid-reactive substances (TBARS) content. Collectively, these results indicate that reduced ScLOR16 transcript levels are associated with enhanced cold and drought tolerance, accompanied by alterations in antioxidant defense and osmoprotection-related physiological markers. This study yields new insights into the evolution and stress-related functions of the ScLOR family.
The intestinal immune system is essential for insects to defend against pathogenic infections, while the dual oxidase-reactive oxygen species (DUOX-ROS) pathway is a key component. However, the role of the DUOX-ROS pathway in Bombyx mori against Nosema bombycis, a significant pathogen of this species, remains poorly characterized. In this study, four core components of the DUOX-ROS pathway in B. mori (BmGαq, BmPLCβ1, BmPLCβ4, and BmDUOX) were identified using bioinformatics. Pathogen induction experiments showed significant upregulation of BmDUOX and increased ROS production following N. bombycis infection. Immunofluorescence and antibody-blocking assays demonstrated that BmDUOX localizes to the plasma membrane and is essential for inhibiting spore adhesion and invasion. This study provides the first systematic evidence of DUOX-ROS-mediated anti-microsporidian immunity in B. mori, which may provide a theoretical basis for the future development of ROS-based disease control strategies in sericulture.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors, now affecting approximately 1 in 31 children. While traditionally defined behaviorally, ASD is increasingly understood as a disorder of brain connectivity arising from altered synaptic formation and refinement. This narrative review synthesizes evidence on neuroimmune dysregulation in ASD, focusing on immune-mediated synaptic pruning mechanisms. We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science (2010–2026), prioritizing high-impact peer-reviewed research. Convergent findings suggest that the classical complement cascade (C1q-C3) tags specific synapses for elimination, while microglia participate in the phagocytic removal of tagged connections. Genetic studies have reported associations between ASD and variants in complement-related genes (C1q, C3, CR3, and C4A, although the strongest evidence for C4A-mediated pruning comes from schizophrenia research), as well as in microglial function genes (TREM2, PTEN, SHANK3). Neuroimaging reveals a dynamic pattern of local hyperconnectivity transitioning to long-range hypoconnectivity during development, particularly affecting prefrontal, insular, and cerebellar regions. Systemic inflammation, including gut–brain axis dysbiosis and maternal immune activation, may amplify neuroimmune dysregulation. We conclude that ASD can be understood, in part, as a disorder of synaptic immunology, where disrupted neuroimmune communication during critical developmental windows may contribute to altered connectivity. The complement–microglia axis therefore represents a potential mechanistic target for future therapeutic investigation.
Canavanine (CAN) is a nonproteinogenic amino acid, synthesised by many legumes (e.g., alfalfa, hairy vetch) and acts as a strong inhibitor of root growth. Thus, CAN may be considered as an allelopathic compound, influencing natural and agroecosystems. CAN is a structural analogue of arginine (Arg), so its toxicity results from its primary mode of action due to interference with Arg-dependent processes, especially incorporation into proteins instead of Arg. The aim of the work was to investigate the impact of CAN (10, 50 µM) treatment (24 or 72 h) on Arg catabolism and content of polyamines (PAs) in the roots of tomato (Solanum lycopersicum L.) seedlings. In the roots of plants cultured in the presence of CAN for 72 h, whosegrowth was completely inhibited, arginase activity and transcript levels of ARG1 and ARG2 were elevated, while ornithine (the product of Arg catabolism by arginase) content was low. CAN application resulted also in decreased total PAs level and increased relative contribution of spermine in the roots of tomato seedlings. CAN-induced alterations in PAs content in the roots were accompanied by changes in transcript levels of genes related to PAs synthesis (SPMS, SPDS) and PAs catabolism (PAO1).
Background: To conserve wild populations and ensure a sustainable supply of musk, China initiated the captive breeding of forest musk deer. The temporal dynamics of gut antibiotic resistance gene (ARG) profiles in captive forest musk deer along a breeding duration gradient remain poorly characterized. Methods: In this study, we employed metagenomic sequencing to systematically characterize the profiles and potential mobility of ARGs. Samples were divided into short-term, medium-term and long-term groups according to breeding durations. Results: A total of 331 ARG subtypes and 71 mobile genetic element (MGE) subtypes were annotated across all samples. ARG Shannon diversity differed overall across groups (Kruskal-Wallis, p = 0.03); Bonferroni-adjusted Dunn’s test showed no significant pairwise differences. PCoA (Bray–Curtis) demonstrated distinct separation of the ST group (p = 0.002), and shared core ARG subtypes gradually increased with extended breeding years. A strong positive correlation between ARG and MGE abundances was identified (r = 0.85, p = 0.0001). In total, 63 contigs carrying co-localized ARG-MGE complexes were recovered. The ST group contained the highest proportion of such contigs. The ST group displayed tight physical ARG-MGE linkage within 1–3 kb genomic intervals. Conclusions: Our results reveal that breeding duration is associated with the gut ARG characteristics of captive forest musk deer. Short-term captivity has higher ARG-MGE co-localization, suggesting a higher possibility of mobilization.
