Abstract: Background/Objectives: Parvovirus infection cause sever diseases in both feline and ca-nine species, mostly affects adult cats and dogs, but cause higher risk in the kittens and puppies. This virus is known to be contagious; the simple way of spreading occurs through food and shelter as well as hands and clothing of people. The recovered species may continue to shed parvovirus in their feces for an extended period, leading to severe environmental contamination. There is no universal vaccine available that protect dogs and cats against parvovirus infections. The main goal of this study is to design a pan parvovirus multiepitope DNA based vaccine that could be administered to dog and cats. Methods: We utilized AI-machine learning incorporated server tools such as IEDB and NetMHCpan to predict B-cell and T-cell epitopes. VaxiJen and ToxinPred were used to analyze immune characteristic features and docking with feline alleles using HADdock server. Following, the immune response and stability of vaccine construct was confirmed with disulfide engineering, Normal mode analysis and molecular docking, and dynamic simulations were done with Toll like receptors of both feline and canine (TLR4 and TLR5) for 50ns. The triggered immune response was determined with immuno-simulation (ImmSim) and their activity in biological environment was reinforced with in silico cloning. Results: The B cell epitopes (NS1 - 9, NS2 - 4, VP1- 12 and VP2- 9) predicted with IEDB database were subjected to antigenicity prediction. MHC class I and IFN prediction and MHC class II and IL-4 prediction were done with IEDB and NetMHCpan. The T cell epitopes showed high binding affinities with the feline alleles. The final vaccine was de-signed by combining the top-ranked B-cell epitopes T- cell epitopes, filtered from high antigenic, non-allergic, non-toxic and good solubility, and with the better binding affinity score of the structural and non- structural proteins (NS1, NS2, VP1 and VP2) of feline and canine parvoviruses through linkers and adjuvants. The disulfide bond prediction and Normal mode analysis showed our vaccine construct are stable and flexible. The molecular docking analysis was performed between the designed vaccine epitopes and the TLRs (TLR4 – feline and TLR5 – canine) with Biovia Discovery Studio using Zdocker, it showed the better binding interaction with value of 22.26 (Zdock score), -47.409 (Zrank score) for feline and 16.54 (Zdock score), -134.295 (Zrank score) for canine. Conclusions: The pan multi-epitope DNA based vaccine combining the four major structural proteins (NS1, NS2, VP1 and VP2) possess dual purpose to protect both feline and canine species against the parvovirus were designed and constructed. The molecular docking and dynamic simulation analysis showed higher binding affinities and stable conformation with canine (TLR5) and feline (TLR4) toll like receptors. Though computational analysis will support us to predict the more precise top-ranked epitopes and their immuno-antigenic properties, further experimental validation will be required to be used against those viruses.

Abstract: Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) severely threatens global banana production. An endophytic Streptomyces strain 7‑1, isolated from the roots of Peliosanthes macrostegia, exhibited strong antifungal activity against Foc TR4 (inhibition rate: 79.75%) and broad-spectrum activity against 12 plant pathogenic fungi. The crude extract of strain 7‑1 inhibited Foc TR4 mycelial growth in a dose-dependent manner (EC₅₀ = 69.20 μg·mL⁻¹) by disrupting cell wall/membrane integrity, inducing mycelial damage, spore apoptosis, nucleic acid leakage and membrane lipid peroxidation. Pot experiments showed strain 7‑1 achieved 63.15% biocontrol efficacy against banana Fusarium wilt, promoted banana growth, enhanced root defense enzyme activities (POD, PPO, PAL), and regulated rhizosphere microflora by enriching beneficial microbes (Bacillus) and reducing Fusarium abundance. Metabolomic analysis identified natamycin as the major active metabolite (EC₅₀ = 8.58 μg·mL⁻¹), which exhibited similar inhibitory effects to the crude extract. Hydroponic experiments confirmed natamycin controlled banana Fusarium wilt with 34.91% efficacy at 1 × EC₅₀. In conclusion, Streptomyces sp. 7‑1 is an environmentally friendly biocontrol strain inhibiting Foc TR4 via direct pathogen damage and indirect regulation of plant defense/rhizosphere microflora. Natamycin has potential as an agricultural fungicide, providing a new candidate and theoretical basis for sustainable control of banana Fusarium wilt.

Abstract: Background: Distinguishing genuine kinase–substrate motifs from background noise is a growing challenge, as mass spectrometry (MS) -based global phosphoproteomics identifies a rapidly expanding set of phosphorylation sites. One of the major limitations is selecting an appropriate background model that systematically controls both tech-nical and biological sources of bias. Although using the entire proteome as a back-ground in FASTA format considers the overall amino acid composition, it is still prone to biases from protein abundance and the uneven distribution of sequence space (par-ticularly around low-abundance proteins). By contrast, internal background methods can control experiment-specific detection biases, but they may not fully capture resi-due-specific compositions or general trends in phosphorylation. Methods: I develop a Dual-Background Enrichment (DBE) strategy, which involves analyzing motif en-richment against two distinct background models: (1) A residue-heterogeneous inter-nal background composed of phospho-motifs centered on the residue, e.g., serine (S) motifs, against threonine (T) and tyrosine (Y) centered motifs. (2) A FASTA back-ground that includes all canonical S, T, and Y sites from the reference proteome. Re-sults: Motifs are classified as high confidence if they meet statistical significance (q ≤ 0.05) against both background models. Conclusion: By applying the DBE strategy to a large-scale phosphoproteomics dataset, we distinguish motifs driven by amino acid composition (enriched in FASTA background only) from those reflecting kinase sub-strate specificity (enriched in both backgrounds). This dual-reference approach reduces false positives arising from sequence composition bias and identifies high-confidence candidate kinase recognition motifs.

Abstract: Medicinal plants have long served as a source of therapeutic agents in Libya and worldwide. This study investigated the in vitro antibacterial activity of twenty-two medicinal plant species against a panel of pathogenic bacteria previously isolated from food of animal origin in Libya. Plant materials were collected or purchased from different regions of Libya and extracted using three solvents of varying polarity: methanol, petroleum ether, and ethyl acetate. The extracts were screened for antibacterial activity against Escherichia coli (EC 56, EC 184), Staphylococcus aureus (SA 121), Klebsiella pneumoniae (KP 243), and Bacillus cereus (BC 4) using the agar well diffusion method. Extracts showing inhibition zones >11 mm were further evaluated for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth microdilution method. Initial screening revealed that extracts from Thymus capitatus, Punica granatum, Syzygium aromaticum, Cinnamomum verum, Rosmarinus officinalis, and Myrtus communis exhibited notable antibacterial activity. The strongest effects were observed with petroleum ether and ethyl acetate extracts. Extracts of C. verum (R2, R3) and S. aromaticum (P2) showed the lowest MIC values, reaching 1.875 mg/mL against S. aureus (SA 121) and B. cereus (BC 4). MBC values were generally one- to two-fold higher than MIC values, indicating predominantly bactericidal effects. B. cereus (BC 4) was the most susceptible organism, whereas most extracts showed limited or no activity against E. coli strains. These findings confirm the strong antibacterial potential of several medicinal plants, particularly C. verum (cinnamon), S. aromaticum (clove), and T. capitatus (thyme). The results support their traditional use and highlight their potential as sources of natural antibacterial agents and food preservatives. Further studies are required to isolate and characterize the active compounds.

Abstract: This review summarizes mechanisms regulating mRNA translation under cellular stress and highlights design strategies to improve translation efficiency and stability in the gene therapy of human diseases. mRNA-based therapeutics are emerging as a versatile gene therapy platform enabling transient and controllable expression of therapeutic for the treatment of cancer, genetic disorders, and inflammatory diseases. The efficacy of mRNA-based gene therapy is strongly influenced by sequence design, chemical modifications, and structural features. Evidence shows that rational mRNA engineering can significantly enhance translation efficiency even under stress conditions that impair canonical protein synthesis, as observed in many pathological states. Cellular stress activates regulatory pathways that suppress global translation; however, optimized mRNA constructs can partially bypass these inhibitory mechanisms, enabling sustained protein expression. By improving mRNA stability and resistance to stress-responsive translational control, robust therapeutic protein production can be achieved even in challenging cellular environments. These advances position mRNA engineering as a promising component of next-generation gene therapy, offering new opportunities for effective treatments of human diseases.

Abstract: Pathogenic missense variants cause disease through two mechanistically distinct routes: structural destabilization leading to protein misfolding and degradation, or functional disruption of a stably folded protein. Despite the clinical importance of this distinction — pharmacological chaperones rescue misfolded proteins, while functionally defective proteins require gene therapy or enzyme replacement — no existing framework predicts which mechanism underlies a given variant. All current tools, from SIFT and PolyPhen-2 to AlphaMissense, predict pathogenicity but not mechanism.Here we show that the elemental composition of a protein’s amino acids, classified by dominant biophysical property, predicts misfolding mechanism from sequence alone. We map each amino acid to one of five elemental classes: charged residues (Agni), flexible residues (Vayu), hydrophobic residues (Prithivi), polar residues (Jal), and aromatic residues (Akasha). This classification is inspired by and named after the Panchamahabhuta system of classical Indian natural philosophy, whose five-element grouping aligns with the five dominant thermodynamic forces governing protein stability. The elemental composition profile of a domain — its elemental constitution (Prakriti) — explains 36.4% of variance in domain biological function across 14 functional classes (η² = 0.364, F = 18, p = 9.99×10⁻³³, n = 420 domains) without any machine learning.Applying this framework to 64,387 VAMP-seq stability measurements across 11 disease proteins, we derive a substitution risk hierarchy: mutations introducing charged residues into hydrophobic cores (Prithivi→Agni) cause misfolding in 57.5% of cases versus 21.1% for Agni→Prithivi. Secondary structure context reveals a 3.7-fold gradient — hydrophobic and aromatic residues in β-strands misfold at 51–52% when mutated; charged residues in turns at only 14%. Proteins whose domain composition conflicts with biological function — compositional discord (Vishamavet) — carry pathogenic variants at 91.8% versus 59.9% in concordant proteins (OR = 7.8, p < 10⁻¹⁵).Key finding: structured-position hydrophobic/aromatic residues misfold at 3.7× the rate of loop charged residues — mechanistic information absent from all conservation-based predictors.We introduce BhutaFormer, a transformer architecture that encodes sequence context as Bhuta tokens and learns elemental interaction grammar via multi-head self-attention, achieving AUROC = 0.77 overall and 0.76 on within-class (Tanmatra) variants — a 13.5 percentage point improvement over Random Forest. On ProteinGym DMS abundance assays, BhutaFormer achieves Spearman ρ = 0.29 for training-distribution proteins, exceeding the Site-Independent baseline (ρ = 0.175) without evolutionary alignment, structural data, or large language model pre-training.

Abstract: Metagenomic analysis of Antarctic soils provides a key perspective on the microbial diversity of one of the most extreme ecosystems on Earth, where microorganisms dominate ecological processes, although their diversity and distribution remain less understood than those of macroscopic eukaryotes. This study aimed to identify bacteria present in Antarctic soils using a metagenomic approach. Soil samples were obtained from the sample bank of the Escuela Superior Politécnica Agropecuaria de Manabí and were collected during an expedition conducted in 2014 on four islands: Greenwich, Dee, Barrientos, and Torre. The analysis included DNA extraction, amplification of the 16S rRNA gene by polymerase chain reaction (PCR) using specific primers, and sequencing on the Illumina MiSeq platform (Macrogen©). These techniques enabled reliable identification of the microbial populations present. The results revealed the predominance of several bacterial phyla across all four islands, with Actinomycetales (36.60%), Proteobacteria (20.03%), Firmicutes (17.53%), and Bacteroidetes (6.91%) being the most abundant. In addition, Antarctic soil metagenomes indicated the potential access to novel genes encoding enzymes with possible biotechnological and industrial applications. Overall, these findings highlight Antarctic ecosystems as reservoirs of valuable genetic resources and underscore their importance for the long-term development of biotechnological applications, without extrapolating conclusions beyond the results obtained.

Abstract: Spent mushroom substrate (SMS), the main by-product of mushroom production, is rich in valuable compounds that could be recovered by ultrasound-assisted extraction (UAE) and exploited as fat-mimetic functional ingredients in food formulations. In this study, low-fat cookies prototypes were developed by incorporating a dietary fiber extract obtained from SMS using UAE. The extraction process was optimized following a Box–Behnken experimental design, identifying optimal conditions at a specific energy input of 200 J/mL, a particle size of 2 mm, and a solute-to-solvent ratio of 1:27, yielding a dietary fiber recovery of 30.82%. The optimized SMS extract exhibited high oil-holding capacity (1.39 g/g), emulsion stability (80%), and foaming capacity (83.55%). Four cookie formulations were evaluated, among which G1 (50% fat replacement) showed the best balance between consumer acceptability and an improved nutritional profile, characterized by higher protein (8.4 g/100 g), total dietary fiber (7.10 g/100 g), and mineral contents. Notably, G1 cookies displayed a significant reduction in predicted glycemic index, decreasing from 83.84 in the control to 69.65. Overall, these results demonstrate that optimized SMS-derived dietary fiber is an effective functional ingredient for the development of low-fat, high-fiber, and reduced-glycemic cookies, contributing to the valorization of agro-industrial by-products within a circular economy framework.

Abstract: Background/Objectives: Obesity and menopause are major determinants of skeletal deterioration; however, their combined effects on bone remodeling and associated cellular bioenergetics remain incompletely understood. This study aimed to determine whether obesity induces osteoporotic alterations under both estrogen-replete and estrogen-deficient conditions and to evaluate the therapeutic potential of dental tissue–derived mesenchymal stem cells (D-MSCs). Methods: Female mice were subjected to ovariectomy (OVX) and/or high-fat diet (HFD) feeding for 16 weeks to establish obesity-associated osteoporosis models. D-MSCs were administered intraperitoneally at defined intervals. Body weight and serum leptin levels were measured to assess metabolic status. Femoral tissues were analyzed by quantitative real-time PCR for estrogen receptors (ERα, ERβ), inflammatory markers (Il-1β, Tnf-α), mitochondrial regulators (Pgc1α, Pgc1β), and the OPG/RANKL ratio. Histological analysis was performed to evaluate bone marrow adiposity. Results: HFD significantly increased body weight and serum leptin levels in both intact and OVX mice. Obesity was associated with reduced expression of ERα and ERβ, decreased Pgc1α levels, and a lower OPG/RANKL ratio, accompanied by increased Il-1β, Tnf-α, and Pgc1β expression. D-MSC administration attenuated body weight gain and reduced leptin levels, particularly in OVX mice. In femoral tissue, D-MSC treatment restored estrogen receptor expression, increased Pgc1α, decreased Pgc1β, and normalized the OPG/RANKL ratio. In addition, inflammatory marker expression and bone marrow adiposity were reduced following MSC administration. Conclusions: Obesity induces bone remodeling dysregulation under both intact and estrogen-deficient conditions, characterized by altered estrogen signaling, inflammatory activation, and mitochondrial imbalance. D-MSC administration was associated with partial restoration of these alterations, suggesting a potential role in modulating metabolic and skeletal homeostasis in obesity-associated bone loss.

Abstract: Background: Neuropathic pain (NP), a debilitating condition from nervous system le-sions, is poorly managed by current therapies. The cingulate cortex is crucial for affec-tive pain processing, yet a comprehensive spatiotemporal understanding of its molec-ular changes in NP is lacking. Methods: This study performed RNA sequencing to pro-file transcriptomic alterations in the anterior cingulate (ACC) and midcingulate (MCC) cortices of mice at two and four weeks after spared nerve injury. Bioinformatics anal-yses, including differential expression, functional enrichment, weighted gene co-expression network analysis, and protein-protein interaction (PPI) network con-struction, were employed. Results: We identified widespread, time-dependent tran-scriptional dysregulation in both regions, with differentially expressed genes increas-ing over time. Analyses confirmed central roles for synaptic plasticity and neuroin-flammatory pathways. Importantly, we uncovered significant dysregulation in prote-ostasis and mitochondrial function pathways, mechanisms shared with neurodegen-erative diseases. PPI analysis identified stage-specific hub genes (e.g., early interfer-on-stimulated genes and late ribosomal proteins in ACC; persistent extracellular ma-trix components in MCC). Conclusions: This study provides a detailed transcriptomic atlas of the cingulate cortex in NP, reinforcing known mechanisms while elucidating novel dysregulation in protein homeostasis and mitochondrial pathways. The findings highlight convergent pathophysiology with neurodegeneration and offer a new theo-retical framework with potential therapeutic targets for chronic NP.

Abstract: To screen high-quality porcine-derived lactic acid bacteria for swine production, this study compared growth performance, acid production, acid and bile salt tolerance, and genome characteristics of Lactiplantibacillus plantarum (MRS002), Lactobacillus amylovorus (MRS003), and Ligilactobacillus salivarius (MRS004). All three strains showed typical anaerobic growth. L. amylovorus had a longer growth cycle and higher biomass, while L. plantarum and L. salivarius grew faster and produced more acid, with pH values reaching 4.2 and 4.3 at 24 h. L. plantarum and L. salivarius also exhibited higher survival rates under 0.3% bile salt and pH 2.0 stress. Genome annotation revealed that more than 50% of genes were related to metabolism in all strains. L. plantarum possessed the most comprehensive metabolic and stress-resistance gene networks; L. amylovorus was enriched in starch-degradation pathways; and L. salivarius showed unique advantages in aromatic amino acid metabolism. In summary, L. salivarius MRS004 displays superior probiotic traits, L. plantarum MRS002 has broad adaptability, and L. amylovorus MRS003 is suitable for high-starch feed fermentation. This study provides theoretical support and strain resources for probiotic development and antibiotic-free breeding.

Abstract: Autocatalytic sets are chemical reaction networks in which the molecules mutually catalyze each other's formation supported by an ambient food set. They are believed to have played an important role in the origin of metabolism and life, and have been studied extensively both theoretically and experimentally. Autocatalytic sets often consist of a hierarchical structure of smaller and smaller autocatalytic subsets. Of particular interest are irreducible autocatalytic sets and closed autocatalytic sets. Previously, it has been shown that finding {\it all} such autocatalytic subsets is, in principle, intractable. Here, several algorithms are presented to enumerate irreducible and closed autocatalytic sets, either exhaustively (but only practical in limited cases) or in the form of a random sample. Their implementation in a C++ program, made available as a GitHub repository, is then tested on instances of a computational model of chemical reaction networks known as the binary polymer model.

Abstract: Containerized ornamental plant production requires efficient irrigation strategies to balance plant quality with water and nutrient conservation. This study evaluated the effects of different leaching fraction (LF) levels (0%, 20%, 40%, and 60%) on plant growth, ornamental quality, water use, and macronutrient leaching in off-season potted Curcuma cv. ‘Jasmine Pink’. Irrigation volumes were determined using crop coefficient (Kc)-based estimates derived from evaporation pan measurements. The results showed that the highest LF level (60%) significantly improved several ornamental quality traits, including flower number per cluster, leaf greenness, specific leaf area, and compactness index, while also increasing aerial dry weight and photosynthetic performance during the flowering stage. These improvements were associated with reduced substrate electrical conductivity, indicating that higher LF might effectively mitigated root-zone salt accumulation and promoted favorable physiological conditions for plant growth. However, increasing LF also resulted in greater irrigation water consumption and higher macronutrient losses through leachate, particularly for potassium. In contrast, lower LF treatments (0–20%) improved water use efficiency and reduced nutrient losses but showed moderate salt accumulation in the root zone, which slightly limited photosynthetic performance and ornamental development. Overall, the results indicate that a higher LF (60%) provides optimal plant growth and ornamental quality for off-season potted Curcuma production, although integrated strategies may be required to reduce water and nutrient losses. These findings provide practical insights for optimizing irrigation management in container-grown ornamental crops.

Abstract: Salinity represents a critical agricultural threat that reduces the productivity of several crops. Tomato (Solanum lycopersicum), recognized as the world´s second most significant horticultural commodity globally, is salt-sensitive. This research evaluated seed priming treatments (hydro, halo, bacterio, and halo-bacterio) at different phenological stages under two salinity conditions (0 and 16 mM NaCl) as a biotechnological alternative to mitigate salt stress and increase production. Using physiological variables and multivariate statistical analyses, this research demonstrated that priming treatments modified the physiological, nutritional, and productive metabolism of tomato plants. Bacteriopriming, using an endophytic and halophytic bacterial consortium isolated from halophytes, enhanced germination variables and N, P, Ca and Zn absorption in seedlings. In the vegetative and reproductive stage and under stress, halo-bacteriopriming consistently enhanced concentrations of K, Mg, and Zn in leaves and fruits, but decreased Na absorption. This nutritional balance allowed not only a higher concentration of chlorophyll but also a significant increase in yield and beta-carotene concentration in tomato fruits. For the first time, this research demonstrated that the halo-bacteriopriming with this kind of bacteria is a biotechnological strategy to mitigate saline stress, optimizing not only tomato growth, but also its nutraceutical quality. It significantly outperformed the plant response in all stages of development compared to those from control, hydro, and halo-primed treatments.

Abstract: Background/Objectives: Glioblastoma (GBM) remains a lethal primary CNS malignancy with limited response to immunotherapy. Adoptive cellular therapy (ACT) improves survival in preclinical models, yet tumors ultimately recur. While T cell exhaustion is a common mechanism of resistance, the contribution of dendritic cell (DC) dysfunction remains unclear. We aimed to define mechanisms of immune escape following ACT, focusing on DC function and the role of hypoxia. Methods: Using a murine glioma model (KR158B), mice were treated with ACT consisting of tumor RNA–pulsed DC vaccines and adoptively transferred T cells. Tumor-infiltrating immune populations were analyzed by flow cytometry. DC function was assessed using T cell activation assays. Bulk RNA sequencing and gene set enrichment analysis were performed on sorted DCs. Hypoxia was modeled in vitro, and HIF1α was perturbed using CRISPR-mediated knockout. Results: ACT significantly increased survival but did not prevent tumor recurrence. Escaped tumors contained abundant cytotoxic, non-exhausted T cells, indicating that T cell dysfunction was not the primary driver of resistance. Instead, tumor-associated DCs exhibited impaired T cell activation despite preserved antigen uptake. Transcriptomic analyses revealed reduced antigen presentation and co-stimulatory signaling, alongside increased expression of tolerogenic factors. ACT-treated tumors demonstrated heightened hypoxia pathway activation, with elevated HIF1α expression in DCs. Hypoxia induced DC tolerogenic programs and reduced their ability to activate T cells, an effect partially reversed by HIF1α disruption. Increased immune infiltration and inflammation following ACT further amplified hypoxia signaling. Conclusions: DC dysfunction is a key mechanism of immune escape following ACT in glioma. Hypoxia-driven tolerization of DCs impairs sustained anti-tumor immunity, highlighting the hypoxia–DC axis as a promising therapeutic target to enhance immunotherapy efficacy.

Abstract:

Extracting high-molecular-weight (HMW) DNA from cactus tissues remains technically challenging due to the abundance of mucilage, pectins, polyphenols, and other metabolites that compromise DNA purity, increase viscosity, and reduce integrity, thereby limiting its suitability for long-read sequencing. This constraint is particularly relevant in Selenicereus megalanthus, a crop of increasing agronomic and genomic importance for which optimized protocols for third-generation sequencing remain limited. Here, we compared four CTAB-based DNA extraction protocols using dehydrated cladode tissue and evaluated DNA quality using NanoDrop spectrophotometry, Qubit fluorometry, agarose gel electrophoresis, and functional validation via sequencing on the Oxford Nanopore PromethION 2 Solo platform. Among the tested methods, our proposed optimized mucilage-adapted CTAB (MuCTAB) protocol, comprising 4% CTAB, 4% PVP-40, 0.5% β-mercaptoethanol, and proteinase K, showed the best overall performance. MuCTAB yielded the highest dsDNA concentration (239.63 ± 34.37 ng/µL), optimal purity ratios (A260/A280 = 1.96 ± 0.05; A260/A230 = 2.01 ± 0.01), and superior DNA integrity. Nanopore validation confirmed its effectiveness, producing the highest sequencing yield (84.2 Gbp), read count, N50 (40.3 kbp), and maximum read length (1.9 Mbp). Overall, MuCTAB represents a low-cost, reproducible, and efficient method for HMW DNA extraction from mucilage-rich pitahaya tissues and other recalcitrant plant species.

Abstract: Interleukin-17A (IL-17A) is a proinflammatory cytokine that plays a crucial role in immune responses and tissue homeostasis. The expression of IL-17A is strictly regulated by transcription factors including RORγt and is mainly produced by Th17 cells, γδT cells, and innate lymphoid cells. IL-17A signals through a heterodimeric receptor complex consisting of IL-17RA and IL-17RC, leading to the activation of NF-κB and MAPK pathways. Recent studies have highlighted its functions in the central nervous system, with reported associations with multiple sclerosis and autism spectrum disorder. Furthermore, the development of IL-17A inhibitors has progressed significantly, showing high therapeutic efficacy particularly in autoimmune diseases. This review provides an overview of current knowledge regarding IL-17A, from its molecular characteristics to clinical applications.

Abstract: ATP-binding cassette (ABC) transporters constitute one of the largest membrane pro-tein superfamilies, yet the structural and evolutionary properties of their non-domain re-gions remain poorly characterized. To elucidate the diversity of these non-canonical re-gions across evolutionary lineages, we analyzed intrinsic disorder, site-specific selection, and predicted post-translational modification (PTM) sites across five architectural classes comprising 1,581 prokaryotic and eukaryotic sequences. Linker and flanking regions were consistently more disordered than transmembrane and nucleotide-binding domains across all architectures. Disorder fraction differed significantly among region types after phyloge-netic correction (Pagel's λ ≈ 0.97). Predicted PTM sites are enriched in disordered non-domain segments, with N-linked glycosylation and phosphoserine showing the strongest positive enrichment; 140 sites satisfied a tiered conservation criterion (Mu-siteDeep score ≥ 0.5; cross-species conservancy ≥ 30%), including 40 high-confidence or moderate-confidence sites (conservancy ≥ 50%) as well as novel phosphotyrosine candi-dates in half transporters and NBD-only proteins. Site-specific selection analyses indicated that episodic positive selection was concentrated at inter-domain boundaries, whereas NBD cores were subject to pervasive purifying selection. Together, these findings establish that non-canonical regions of ABC transporters are evolutionarily dynamic and harbor conserved predicted modification sites, supporting their roles as potential regulatory inter-faces rather than passive structural linkers.

Abstract: This article reviews current knowledge in comparative immunology and presents updated hypotheses on the evolution of the immune system in jawed vertebrates. It focuses on the co-option of the RAG transposon in the origin of the V(D)J recombination system, proposed to have occurred in two stages. Initially, the RAG transposon, along with other eukaryote-specific transposon such as HAT, interacted with host genes in early eukaryotes, leading to a new transposition mechanism. Subsequently, RAG and host genes were integrated into the V(D)J recombination system, representing a major evolutionary innovation. The broader implications of this events are also considered. Earlier hypothesis suggest that the establishment of the V(D)J recombination system contributed to MHC polymorphism. Phylogenomic evidence indicates that key immune components, including MHC, T-cell receptors (α,β and γ,δ), and immunoglobulins, existed in ancestors and later expanded through gene duplication, forming multigene families with diverse functions. Their proteins products interact with other immune molecules to regulate immune responses. While some retained original functions, others evolved new roles through neo-functionalization. Overall, the co-option of the RAG transposon played a critical role in shaping the immune system of jawed vertebrates by driving innovation in both adaptive and innate immunity.

Abstract: As the global average temperature increases, heat stress (HS) caused by high temperatures has become a key constraint to the development of the poultry industry. As the primary metabolic organ, HS can induce liver injury in chickens, thereby compromising food safety. However, the precise mechanisms underlying HS -induced liver injury remain to be elucidated. The objective of this study is to explore the impact of HS on liver damage, oxidative stress, the Keap1-Nrf2 pathway, ferroptosis and cuproptosis in chickens. A total of 70 chickens were selected for this experiment and divided into a CON group and HS group: the CON group was reared in a normal-temperature environment (24 ± 1 ℃), whilst the HS group was reared in a high-temperature environment (33 ± 1 ℃). The findings of the study suggested that HS has the potential to induce liver dysfunction, oxidative stress, and disruption of the Keap1-Nrf2 pathway. HS has been demonstrated to induce Fe2+ accumulation in chicken livers, inhibit the expression of FTH1, FSP1, SLC7A11 and Gpx4, and simultaneously upregulate the expression of CD71, PTGS2 and ACSL4, thereby promoting ferroptosis. Furthermore, Cu2+ accumulation in the liver upregulates HSP70, DLAT and Lip-DLAT levels and downregulates the expression of ATP7B, PDH1A, PDHB, PDK4, DLST and FDX1, thereby inducing cuproptosis. Subsequent correlation analysis revealed that HS can induce ferroptosis and cuproptosis via the HO-1/FDX1/Gpx4 pathway. This finding provides new insights into the mechanisms underlying HS-induced liver injury.