3 Biotech最新文献

Multiple sclerosis is a debilitating demyelinating progressive neurodegenerative disease, that eventually leads to the death of patients. Transcriptomic patient dataset analysis revealed marked alterations in P₂Y₁₂ expression in microglia from individuals with Multiple Sclerosis. Absorption, Distribution, Metabolism, and Excretion (ADME) profiling highlighted clopidogrel, a P₂Y₁₂ inhibitor, as a potentially promising treatment option for advanced stages of the disease. Our previous invitro studies using N9 microglial cells showed that, clopidogrel effectively mitigated TNF-α mediated inflammatory response and chemotaxis. We employed targeted metabolomic analysis of healthy, cuprizone-fed, clopidogrel-treated, and clopidogrel-treated cuprizone-fed mice to understand the metabolic modulation associated with clopidogrel treatment. Our analysis reveals that cuprizone-fed mice show deregulation of metabolic pathways important for lipid, oxidative stress, and biotin metabolism. Notably, clopidogrel modulates metabolic pathways in cuprizone-fed mice particularly involved in lipid, biotin and myelin biosynthesis. Taken together, our earlier findings with N9 microglial cells and current results from the cuprizone-fed mice model suggest clopidogrel as a potential therapeutic agent in Multiple Sclerosis.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04715-0.

Analyses of genomic diversity across the X-chromosome, and its comparison with autosomal diversity, offer valuable insights into the evolutionary dynamics shaping sex-linked genomic architecture. Investigating X-chromosome linked variation can uncover demographic and selective forces that are often undetectable using autosomal markers. In the present study, 50 individuals representing Indian indicine breeds (Ladakhi, Sahiwal, Kangayam, Nelore, and Gir), Chinese indicine breeds (Guangfeng and Wannan), and taurine breeds (Hereford, Simmental, and Hanwoo) were analysed for Xchromosomal diversity. Variant calling and quality filtering resulted in a total of 1,34,617 high-quality single nucleotide polymorphisms. Principal Component Analysis, Admixture modelling, and Phylogenetic construction, revealed a clear genetic differentiation between indicine and taurine groups. Local ancestry inference on the X-chromosome of Ladakhi cattle revealed region-specific introgression and evidence of adaptive admixture from taurine-derived loci which is linked to TRNAV-CAC gene, which influences milk protein content. Analyses of observed heterozygosity, nucleotide diversity, and linkage disequilibrium revealed lower diversity on the X-chromosome relative to autosomes. Extended haplotype homozygositybased selection signatures, namely the Integrated Haplotype Score for within-population and Cross-population Extended Haplotype Homozygosity for between-population comparisons, identified several regions-involved in metabolism, reproduction, disease resistance, and immune response-located in the distal regions of the X chromosome. Overall, this study is the first of its kind in cattle at large scale and provides a foundational framework for future research in X chromosome specific evolutionary biology and functional genomics.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04724-z.

Biochar is a safe soil amendment. To explore the effects of biochar prepared from specific raw materials at different pyrolysis temperatures on the soil properties and bacterial community structure, and to achieve the recycling of livestock and poultry manure and crop straw, different carbonization temperatures of swine manure biochar (350, 500, 650 ℃) and straw biochar (500 ℃) were set up through pot experiments. Compared with normal fertilization, the addition of swine-manure biochar obtained at 500 ℃ could increase the soil pH, total carbon, total phosphorus, total potassium, organic carbon, microbial biomass carbon, water-soluble organic carbon, and readily oxidized organic carbon contents but did not have a significant effect on the soil total nitrogen content. The biochar application could also increase the activities of polyphenol oxidase and beta-glucosidase but decrease protease, and amylase activities. The application of biochar increased the alpha diversity index of the bacterial community. Redundancy analysis showed that the soil organic carbon and protease were key environmental parameters that affect the main gradient of soil bacterial community composition. Biochar can significantly improve soil properties and affect soil bacterial community composition. Soil organic carbon and protease were the key drivers of the soil bacterial community composition changes. The application of biochar to soil may modestly improve its physicochemical properties, enzyme activity, and microbial community composition. The application of biochar is feasible for the improvement of low-nutrient tea orchard soil.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04731-0.

The present study investigated the impact of exogenous elicitor application on enhancing chia seed quality. The application of chitosan (200 ppm) and PGPR consortia (5000 ppm) to black chia resulted in the most notable improvements. Application of chitosan improved swelling factor (12.03 cc g⁻¹), fiber content (44.35 g 100 g⁻¹), and oil content (36.08%). The PGPR consortia maximized α-linolenic acid (ALA) accumulation (66.74%), while methyl jasmonic acid increased protein content (33.17 g 100 g⁻¹). In contrast, elicitor application to white chia exhibited a distinct response pattern. Kinetin (100 ppm) recorded the highest swelling factor (11.98 cc g⁻¹), PGPR elevated protein content (34.03 g 100 g⁻¹), and chitosan increased fiber (49.09 g 100 g⁻¹) and oil content (35.78%). The study demonstrated a significant enhancement in the accumulation of secondary metabolites, specifically total phenols and flavonoids. In summary, the application of chitosan, PGPR consortia, and kinetin significantly improved the functional and nutraceutical qualities of both seed types.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04746-7.

WGCNA was used to identify DR-related PANoptosis genes, and the LASSO, SVM-RFE, and Random Forest machine learning models were then employed to identify key PANoptosis-related genes. The lncRNA-miRNA-TLR3 networks were constructed, and the levels of hub lncRNAs, hub miRNAs and TLR3 were measured in a high-glucose cell model. The luciferase reporter assay was employed to validate the interactions between Gm12610 and miR-758-3p, as well as between miR-758-3p and Tlr3. In the GSE102485 and GSE185011 cohort, TLR3 expression was significantly elevated in the DR samples compared to controls. Data from the GSE236627 cohort indicated a marked upregulation of Tlr3 in retinal microglia of db/db mice relative to normal controls. GSEA results showed that AGE-RAGE signaling pathway in diabetic complications and NF-kappa B signaling pathway were enriched and activated in the high-TLR3 expression (H-TLR3) group. Additionally, M2 macrophage infiltration was reduced in this group. Through the ENCORI and TargetScan databases, two ceRNA networks were constructed: C15orf54/CDKN2B-AS1-hsa-miR-758-3p-TLR3 and CDKN2B-AS1-hsa-miR-374b-5p-TLR3. In vitro experiments validated that high glucose-stimulated microglia showed significantly increased levels of Tlr3 and Gm12610 (mouse CDKN2B-AS1), but decreased levels of miR-374b-5p and miR-758-3p compared to the control group. Luciferase assays confirmed direct binding between Gm12610 and miR-758-3p, and between miR-758-3p and Tlr3. Our study identifies TLR3 as a key PANoptosis-related gene in DR, suggesting it potential as a therapeutic target for DR.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04720-3.

Neurological complications of COVID-19 encompass acute syndromes and persistent post-acute sequelae, yet their mechanistic basis remains incompletely defined. Integrated clinical, neuropathological, neuroimaging, and molecular evidence indicates that SARS-CoV-2-associated neurological injury is driven predominantly by receptor-mediated immune and vascular mechanisms rather than widespread productive central nervous system infection. Angiotensin-converting enzyme 2 (ACE2) remains the principal viral entry receptor, while neuropilin-1 (NRP1) facilitates neurovascular and olfactory access in specific contexts. In contrast, CD147 and dipeptidyl peptidase-4 (DPP4) appear to exert indirect modulatory roles through endothelial dysfunction and immune activation rather than acting as dominant neurotropic entry receptors. Toll-like receptors, particularly TLR2, TLR4, and TLR7, amplify neuroinflammatory signaling and contribute to blood-brain barrier disruption, microvascular injury, and sustained microglial activation. Cerebrospinal fluid biomarkers and neuroimaging findings consistently support a dual-pathway model combining limited direct viral presence with predominant immune-mediated injury. Current therapeutic strategies targeting receptor-mediated entry and neuroinflammation remain largely investigational, underscoring the need for biomarker-guided and phase-specific interventions. These findings refine the mechanistic framework of NeuroCOVID and identify translational priorities for acute and long-term neurological management.

This study investigates the neuroprotective potential of the dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin in models of Parkinson's disease (PD). In vitro, sitagliptin (10-80 µM) and vildagliptin (5-40 µM) enhanced mitophagy and modulated autophagy pathway in neuronal cell lines. Sitagliptin (20-80 µM) similarly promoted autophagy in Drosophila larval fat body. In an MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine)-induced mouse model of PD, administration of vildagliptin (15 mg/kg/day) mitigated neuronal loss, reduced microglial activation, and increased tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and striatum. Network pharmacology and molecular docking analyses identified ten key protein targets, with DPP-4, serine/threonine-protein kinase AKT (AKT1) and glycogen synthase kinase-3 beta (GSK3β) emerging as central nodes. These findings indicate that both drugs engage a multi-target network to modulate autophagy and mitophagy, potentially facilitating the clearance of pathogenic protein aggregates and dysfunctional mitochondria. Together, these results position sitagliptin and vildagliptin as promising autophagy-modifying candidates for disease-modifying PD therapy.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-026-04761-8.

This review critically analyses plant adaptive responses to biotic and abiotic stress, with a focus on recent advancements in molecular defense pathways, emerging nanotechnology approaches and CRISPR/Cas-based genome editing strategies. We critically reviewed structural, physiological, biochemical and genetic adaptations. Key regulatory processes include phytohormonal regulation, antioxidants, reactive oxygen species (ROS) signaling and stress-response gene networks are explored along with advances in nanotechnology-based strategies and CRISPR/Cas genome editing. A comparative evaluation of conventional breeding, molecular breeding, and genome-editing approaches highlights the advantages of CRISPR/Cas systems, particularly their precision, efficiency and ability to generate targeted phenotypic changes. In parallel, nanomaterials have shown promise in improved nutrient delivery, protecting cellular structures and enhancing genome-editing efficiency under stress conditions. By integrating nanotechnology and genome-editing approaches with traditional agricultural practices, it may be possible to enhance plant resilience, sustain crop productivity and reduce reliance on chemical inputs. Overall, this review provides a cohesive perspective on how these technologies can be combined to support future crop improvement efforts to tackle climate-induced agricultural challenges.

The neurodegenerative decline of brain with ageing is an acute global demographic problem, as elderly population surges worldwide. However, ageing effect has not been systematically studied for cerebellum, an autonomous part of brain having motor, cognition, language and memory functions. By magnetic resonance investigation, we study brain-ageing process: 177 normal subjects, aged 20-80, with focus on cerebellum, the first larger-scale analysis as we know. We found that for whole brain, both grey-matter/GM and white-matter/WM) volumes deceases with ageing (by ~ 15%). Contrastingly, these volumes remain unexpectedly stable in ageing cerebellum, indicating neuroprotective ability. To estimate neuroplasticity resilience of brain-tissue, we evaluated GM/WM interrelationship, assessed by GM-volume/WM axial-diffusivity. During ageing, the GM/WM interrelationship is comparatively stable in cerebellum, while in whole brain this relationship is much variable (230% increase). We validated the cerebellar neuroprotective ability by epigenetic tissue ageing analysis (DNA-methylation). Ageing retardation-level (years) of brain-tissue follows the neurodevelopmental caudal-rostral-rhinal axis: cerebellum (maximum retardation/neuroprotection), occipital, frontal, and temporal region (minimum). We log-normally plotted ageing-retardation against phylogenic age of that brain region (million-years ago/MYA), and found linear relationship, implying a quantitative evolutionary behaviour, indicating cerebellum's phylogenic antiquity (Cambrian-era ~ 510MYA), which adapted the cerebellum to withstand degenerative damage. Finally, we investigated cerebellum's neurocognitive resilience, enabling focussed development of coordination, tool-making and language, while present-day humans evolutionarily progressed over Neanderthals. We found that humans show maximal cerebellar expansion and depth. Of seminal significance is that cerebellum is a unique paradoxical brain region with peak neuroprotective behaviour, and may have substantial therapeutic rehabilitative biotechnological implications in neurodegenerative disorders.

Hydroxyapatite (HAp) nanoparticles are gaining attention as potential drug delivery systems for Alzheimer's Disease (AD) because of their compatibility with biological systems, stability, and adaptable surfaces. Their small size facilitates effective drug encapsulation and controlled release, while surface alterations with ligands or antibodies enable precise targeting of delivery to the blood-brain barrier (BBB) and to areas affected by amyloid-beta (Aβ) plaques and tau accumulations. HAp nanoparticles are capable of transporting anti-amyloid, anti-tau, and neuroprotective drugs, which increases therapeutic levels and reduces systemic adverse effects. Research shows that HAp nanoparticles can pass through the BBB using adsorptive-mediated and receptor-mediated transcytosis, and methods such as temporarily opening tight junctions or modifying surface charges can further improve their permeability. Drugs can be integrated via co-precipitation, adsorption, or encapsulation techniques, often allowing for pH-responsive release in the acidic environment of diseased brain tissue. Nevertheless, there are still obstacles to address regarding the scalability of production, stability and clearance in living organisms, and the long-term compatibility and safety in neural tissue.