Search Results (88,425)

Hollow mesoporous silica nanoparticles (HSNs) were synthesized via the Stöber method using resorcinol–formaldehyde resin as a template and further developed as a multifunctional nanocarrier for synergistic chemo–photothermal therapy. Docetaxel (DTX) and indocyanine green (ICG) were co-loaded into HSNs as the prodrug and photothermal agent. The loading sequence of these agents can critically affect encapsulation efficiency. Preloading DTX followed by ICG incorporation achieved the highest drug loading (38.65%) and preserved the photoactivity of ICG. The resulting ICG&DTX@NH₂-HSNs exhibited strong and stable near-infrared photothermal conversion, as well as pH- and laser-responsive drug release behavior. In vitro studies confirmed efficient cellular uptake by 4T1 tumor cells and enhanced cytotoxicity compared with single treatments. In vivo experiments demonstrated significant tumor growth suppression in 4T1 tumor-bearing mice, with the greatest effect observed under combined ICG&DTX@NH₂-HSNs and laser irradiation. Importantly, histological analysis of major organs revealed no obvious toxicity, confirming the biosafety of the present nanoplatform. This study confirmed the potential of hollow mesoporous silica-based nanocarriers as safe and effective platforms for combined chemotherapy and photothermal cancer therapy. Full article

Astragalus root rot is a soil-borne disease primarily caused by Fusarium spp., which severely hampers the sustainable development of the Astragalus industry. F. acuminatum is a predominant pathogen causing this disease. To elucidate the genetic variation and adaptive evolutionary characteristics of F. acuminatum from different geographical origins, this study conducted whole-genome resequencing analysis on 28 isolates of F. acuminatum collected from four major Astragalus production regions. Approximately 124.9 Gb of high-quality sequencing data were obtained, and a large number of single-nucleotide polymorphisms (SNPs) were detected. Population genetic analysis revealed that strains from different regions did not form strictly geographically specific clusters, exhibiting a complex mixed distribution pattern. Nucleotide polymorphism analysis indicated that the Dingxi, Gansu (GD) population possessed the highest nucleotide diversity (π) value, reflecting the richest genetic diversity. Fixation index (Fst) analysis revealed significant genetic differentiation (Fst > 0.15) among populations from different provinces, suggesting that geographic isolation may be a contributing factor to restricted gene flow between pathogenic isolates in these regions. Tajima’s D positive values suggest a deviation from neutrality, consistent with balancing selection or population contraction. Ka/Ks analysis further revealed that the majority of genes exhibited Ka/Ks > 1, differing from the typical pattern of purifying selection dominance. This study revealed the genetic variation and selection signals of F. acuminatum isolates from different geographical origins, observed significant genetic differentiation between the Gansu and Ningxia populations, and identified a large number of genes that may be subject to positive selection. Full article

Shiga toxin–producing Escherichia coli (STEC) are important zoonotic pathogens that can disseminate through environmental water systems, yet data from Southern Italy remain scarce. The aim of this study was to investigate the occurrence and genetic characteristics of STEC isolated from surface water samples collected from rivers and lakes in the Apulia region (Southern Italy). A total of 120 samples were processed according to ISO/TS 13136:2012, followed by whole genome sequencing (WGS) for isolate confirmation and characterization. Overall, 20% of the samples were stx-positive in screening. STEC strains were isolated from 4.2% of stx-positive enrichments, corresponding to one sample out of a total of 120 (0.8%). The isolate was identified as O139:H1, carrying the stx2e subtype and belonging to sequence type ST1. Genomic analysis revealed multiple virulence-associated determinants, including the complete F18 fimbrial operon (fedA-F), hlyA, csgA, gad, chuA, yehA-D, and ompT, along with stress-resistance and tellurite-resistance genes. The strain was susceptible to all antibiotics tested. The genomic profile suggests a swine-associated lineage with multiple environmental persistence traits but limited antimicrobial resistance. The detection of a swine-associated STEC strain in surface waters highlights potential environmental dissemination pathways and underscores the importance of continued monitoring within integrated water–livestock surveillance frameworks. Full article

In this paper, we investigate refined level sets associated with branching random walks on the boundary of a supercritical Galton–Watson tree. More precisely, for a prescribed deterministic sequence $\mathbf{s}:=(r_n,{\tilde{r}}_n)$, we introduce refined deviation sets, denoted by $E_{\mathbf{s}}(\alpha ,\beta )$, consisting of boundary points for which the deviations $S_n\mathsf{X}\left(t\right)-\alpha S_n\tilde{\mathsf{X}}\left(t\right)$ and $S_n\mathsf{Y}\left(t\right)-\beta S_n\tilde{\mathsf{Y}}\left(t\right)$ are asymptotically equivalent to $r_n$ and ${\tilde{r}}_n$, respectively, as $n\to \infty$. This setting extends the classical law-of-large-numbers level sets by allowing for controlled deviations around the typical linear behavior of the branching random walks. By constructing suitable inhomogeneous Mandelbrot measures, we establish sufficient conditions under which the sets $E_{\mathbf{s}}(\alpha ,\beta )$ have maximal Hausdorff and packing dimensions. Full article

Traumatic spinal cord injury (SCI) is a severe medical condition, often resulting in permanent disability, with significant impacts on patients’ quality of life and burden on healthcare systems. Current therapeutic approaches for SCI are insufficient, advocating for the development of more effective treatments. As changes in transcriptome post-SCI can provide clues for novel treatment strategies and targets, substantial efforts have been made recently to characterize such transcriptional changes and their spatiotemporal features. This narrative review focuses on how transcriptomics, alone or in combination with other omics data, can contribute to understanding SCI pathobiology and the mechanisms of post-SCI regeneration and guide the development of novel SCI therapies. It covers an arsenal of tools for transcriptomics studies and provides a concise summary of findings from the latest relevant studies (predominantly from 2020 to 2025), representing the major directions in the field. Full article

The Zona Pellucida (ZP) and its structural analogs are evolutionarily ancient extracellular matrix components. These are essential for oocyte protection, species-specific gamete recognition, and prevention of polyspermy across Metazoa. Defined by the conserved ZP-domain—comprising ZP-N and ZP-C subdomains—these glycoproteins self-assemble into fibrillar matrices through tightly regulated polymerization. Mechanisms of the regulated polymerization involve furin cleavage, disulfide bonding, and hydrophobic interactions. Once considered a vertebrate innovation, the canonical ZP-domain— defined by its bipartite ZP-N/ZP-C architecture, eight conserved cysteine residues, and capacity for matrix polymerization—is now recognized as an ancient metazoan extracellular module, with homologs identified in basal lineages including Porifera, Cnidaria, and Placozoa. While ZP-like sequences have been reported in choanoflagellates such as Salpingoeca rosetta, these lack the complete canonical features and are considered distant structural relatives rather than true ZP-modules. There they function in cell adhesion and tissue integrity, suggesting an origin predating the evolution of specialized reproductive coats. Previous phylogenetic analyses across 97 metazoan species have revealed that vertebrate ZP genes arose from ancestral duplications of the canonical ZP-module. Accordingly, they give rise to eight subfamilies (ZP1–ZP4, ZPD, ZPAX, ZPX, ZPY), with lineage-specific expansions, losses, and pseudogenization reflecting adaptations to diverse reproductive strategies. Positive selection in sperm-binding regions of ZP2 and ZP3 drives a rapid adaptive evolution. It underscores coevolutionary arms races with sperm ligands, contributing to reproductive isolation and speciation. In invertebrates such as abalone and insects, ZP-domain proteins mediate analogous functions through lineage-specific elaborations, including tandem repeats and domain shuffling. Post-translational modifications, particularly glycosylation, fine-tune sperm receptor specificity and matrix stability. The functional transition from a general protective barrier in early metazoans to a sophisticated gamete recognition interface in vertebrates exemplifies modular evolution. This synthesis highlights the domain-level deep homology of ZP-domain proteins as a foundational element of metazoan extracellular matrices, repurposed through gene duplication, neofunctionalization, and selection to meet the demands of evolving reproductive modes. These insights bridge evolutionary biology, reproductive medicine, and developmental genetics. However, major gaps remain, including unresolved orthology between vertebrate and invertebrate ZP genes, the relative contribution of glycans versus protein backbone in sperm recognition, and the lack of functional evidence for canonical ZP-domain proteins in insects. Future studies integrating glycoproteomics, single-cell transcriptomics, and CRISPR-based models are needed to resolve these questions. Full article

Pseudomonas aeruginosa is an opportunistic pathogen causing healthcare-associated infections. Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative bacteria. Resistance arises through mutations in two-component systems (TCS) regulating the arn operon. Data on colistin resistance in P. aeruginosa from Pakistan remain limited. A total of 3189 clinical samples (urine, blood, sputum, pus, wound swabs) were cultured. P. aeruginosa was identified by Gram staining, biochemical tests (catalase, oxidase, API 20E), and oprL gene amplification. Antibiotic susceptibility was determined by disk diffusion and MIC strips. Resistance genes (PhoP, PhoQ, PmrA, PmrB, mcr-1, oprD) were detected by PCR and Sanger sequencing. Wild-type protein structures were retrieved from PDB; mutant structures were predicted using AlphaFold3. ANP (phosphoaminophosphonic acid-adenylate ester) was docked using MOE 2019.0102. Of 3189 samples, 384 (12.0%) yielded P. aeruginosa. Wound/pus (38.0%) and surgical wards (30.0%) were the predominant sources. Colistin and polymyxin B showed 99.0% susceptibility (MIC₅₀/MIC₉₀ = 1 µg/mL). High resistance was observed for Piperacillin–Tazobactam (96.4%), Aztreonam (70.6%), and Gentamicin (64.2%). oprD was the most prevalent gene (87.5%), followed by PmrB (54.0%), PhoQ (44.0%), PhoP (36.0%), PmrA (18.0%), and mcr-1 (8.0%). Docking revealed the strongest binding in wild-type PhoQ (1ID0; −12.0 kcal/mol, LYS392), wild-type PmrB (2JSO; −9.8 kcal/mol, ASP37), and wild-type PhoP (2PKX; −9.1 kcal/mol, LYS87/ARG111). Mutant proteins showed reduced binding affinities and dispersed interaction networks. Mutant PhoP formed 16 contacts (strongest −4.3 kcal/mol) versus wild-type PhoP with 13 contacts (−9.1 kcal/mol). Colistin remains highly effective against P. aeruginosa in this setting (99.0% susceptibility). The presence of mcr-1 (8.0%) and high oprD prevalence (87.5%) require continued surveillance. Mutations in TCS proteins reduce ANP binding affinity and alter interaction specificity, suggesting that ATP-competitive inhibitors targeting these kinases merit further investigation and experimental validation. Full article

The expansion of ruminant production has increased methane (CH₄) emissions, highlighting the need for nutritional strategies that improve productivity while mitigating environmental impacts. Yaks, generally considered low CH₄ producers, are increasingly raised under intensive winter-housed systems on the Qinghai–Xizang Plateau, highlighting the need to assess how dietary concentrate-to-forage (C:F) ratios affect both CH₄ emissions and growth performance. This study investigated the effects of three dietary C:F ratios [L-C (48:52), M-C (60:40), H-C (72:28)] on growth performance, ruminal fermentation, microbial diversity (n = 6 per group) and CH₄ emission (n = 3 per group) in winter-housed yaks. The results indicated that average daily gain (ADG) was significantly higher in M-C and H-C, while the feed-to-gain ratio (F/G) was significantly lower in M-C and H-C than in L-C (p < 0.05). Total CH₄ production (g/day) did not differ among treatments (p > 0.05), while CH₄ yield per unit body weight gain (CH₄/BWG) was significantly reduced in M-C and H-C (p < 0.05). The protozoal count was significantly lower in H-C, and the proportions of isobutyrate and isovalerate were significantly higher in H-C and M-C compared with L-C (p < 0.05). 16S rRNA gene sequencing revealed that increasing the C:F ratio reduced the relative abundance of the archaeal genus Methanobrevibacter, while Thermogymnomonas exhibited a significant increase (p < 0.05). Collectively, these findings indicate that increasing the C:F ratio in winter-housed yaks improves growth efficiency and lowers CH₄/kg BWG, with the M-C group showing the most favorable balance between productivity and environmental sustainability. Full article

Background: The phylogenetic placement of the rheophilic glyptosternoid catfish Chimarrichthys kishinouyei within Sisoridae remains insufficiently resolved because mitogenome-derived phylogenetic evidence has been unavailable. Methods: We sequenced, assembled, and annotated the complete mitogenome of C. kishinouyei and reconstructed its mitochondrial phylogenetic relationships using 13 protein-coding genes and two rRNA genes. Results: The mitogenome was a circular molecule of 16,718 bp and contained 37 typical mitochondrial genes, including 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a control region. The genome showed an A + T bias, with an A + T content of 57.27%. Most tRNAs formed typical cloverleaf structures, whereas tRNA-Ser(GCU) lacked a typical DHU arm. Codon usage was biased, and all 13 protein-coding genes had Ka/Ks ratios below 1, consistent with predominant purifying selection. Phylogenetic analyses placed C. kishinouyei within the glyptosternoid lineage and recovered a strongly supported sister relationship with Pareuchiloglanis sichuanensis rather than direct clustering with Euchiloglanis davidi. Conclusions: Phylogenetic analyses based on 13 protein-coding genes and two rRNA genes support the placement of C. kishinouyei within glyptosternoid Sisoridae and indicate that relationships among Chimarrichthys, Pareuchiloglanis, and Euchiloglanis require further testing with broader integrative evidence. Full article

Dysregulation of ribosome biogenesis is increasingly recognized as a hallmark of tumor malignancy, yet its prognostic implications in lung adenocarcinoma (LUAD) remain incompletely characterized. This study aimed to construct a ribosome biogenesis-related prognostic model for LUAD and explore its potential relevance to the tumor immune microenvironment. Single-cell and bulk RNA sequencing data were integrated to identify ribosome biogenesis-related genes (RBRGs), from which a prognostic risk score was established via Cox regression, LASSO regression, and multivariate Cox analyses and validated in two independent GEO cohorts. Associations between the risk score and tumor mutation burden, immune infiltration, and computationally inferred immunotherapy response were systematically evaluated. In vitro experiments were performed to characterize the biological function of RPS19BP1, a key gene in the model. A total of 262 RBRGs were identified, and the derived 14-gene risk score demonstrated prognostic value across three cohorts (TCGA: 1-, 2-, 3-year AUC = 73.08, 72.44, 72.20; GSE68571: 1-, 2-, 3-year AUC = 67.93, 73.24, 77.59; GSE8894: 1-, 2-, 3-year AUC = 75.56, 72.99, 71.77). The low-risk group exhibited a more immunocompetent tumor microenvironment, whereas the high-risk group was associated with an immunosuppressive phenotype. Knockdown of RPS19BP1 significantly attenuated the proliferation, migration, and invasion of LUAD cells. This multi-omics-derived prognostic model showed prognostic potential in retrospective LUAD cohorts, is associated with distinct immune infiltration patterns, and identifies RPS19BP1 as a pro-oncogenic regulator in LUAD. Full article

Lactylation, a recently identified post-translational modification, has been associated with multiple cancer types, including neuroblastoma (NB). The present study aimed to investigate the prognostic significance of lactylation-related genes and to develop a prognostic model to enhance patient risk stratification and guide targeted therapy for NB. In the present bioinformatics study, single-cell RNA sequencing data (GSE137804) were analyzed to quantify lactylation activity in NB cells using the AddModuleScore algorithm based on 371 lactylation-related genes. A total of 142 differentially expressed lactylation-related genes (DELGs) were identified between high- and low-lactylation tumor cells, and these genes were mainly enriched in cell cycle-related pathways. A 14-gene lactylation-related prognostic model was then constructed using the identified DELGs in a training cohort (GSE49710, n = 349) via Cox and LASSO regression, and validated in internal (GSE49710, n = 149) and external (E-MTAB-8248, n = 223) cohorts. The model effectively stratified patients into high- and low-risk groups with significantly different overall survival (OS) outcomes, and its robust predictive performance was confirmed across both validation cohorts. The present study reveals the significant prognostic role of lactylation in NB, and the 14-gene model serves as a novel molecular tool for risk stratification and provides a reference for developing targeted therapeutic strategies for NB. Full article

Steel plate defect detection is confronted with problems such as weak features of small defects, disconnection between physical priors and detection tasks, and semantic inconsistency of multi-scale fusion, which can easily lead to the misdetection of small defects. To solve these problems, this paper proposes a detection method named PG-SalDETR. Firstly, this paper proposes a physics-guided saliency perception mechanism (PGSPM), which transforms physical priors into learnable guidance signals and directly embeds them into the detection network for joint optimization. Secondly, this paper proposes the token sequence saliency perception network (TSSP-Net), which is designed to help improve the perception and representation of small defect features through an asymmetric dual-branch architecture, adaptive fusion, and residual fusion. Thirdly, a two-stage query refinement mechanism (TSQRM) is proposed. Through physically guided offset correction and adaptive multi-scale feature aggregation, it optimizes the query while preserving fine-grained defect details. Finally, the dynamic cross-scale fusion module (LCASF) is proposed. Through the dynamic cross-scale fusion strategy, the semantic inconsistency problem of small defect features in multi-scale fusion is alleviated. Experimental results demonstrate improvements. Compared to Salience DETR, PG-SalDETR achieves an AP increase of 3.8% and 2.6%, and an AP_S increase of 2.8% and 3.9% on the NEU-DET and GC10-DET datasets, respectively. These results indicate the effectiveness of the proposed method for small defect detection on steel plate surfaces. Full article

The Kidney Disease: Improving Global Outcomes (KDIGO) CGA framework remains the essential basis for chronic kidney disease (CKD) classification, risk stratification, and guideline-based therapy. However, eGFR and albuminuria do not always explain the physiological mechanism maintaining the current filtration level or the heterogeneity of treatment responses. This narrative review proposes a hypothesis-generating functional–hemodynamic extension of KDIGO CGA that incorporates renal functional reserve (RFR), blood pressure, volume status, proteinuria phenotype, and selected tubular markers. RFR is discussed as a dynamic stress test of nephron reserve rather than as a replacement for eGFR or albuminuria. A low, zero, or negative RFR may suggest reserve exhaustion or relative hyperfiltration, but its interpretation depends on standardized testing conditions and clinical context. We distinguish established evidence-based therapy—RAAS blockade in albuminuric or hypertensive CKD, SGLT2 inhibition for kidney and cardiorenal protection, and non-steroidal MRA therapy in selected patients—from conceptual sequencing hypotheses such as RAASi-prioritized, SGLT2i-prioritized, early dual, or staged triple renoprotection. The review also summarizes albuminuria as a two-compartment phenomenon involving both glomerular passage and proximal tubular handling of filtered proteins. The proposed framework is not a validated treatment algorithm. It is intended to support physiological phenotyping, interpretation of early eGFR changes, and the design of prospective studies that test whether RFR adds independent prognostic or therapeutic value beyond KDIGO CGA. Full article

Background/Objectives: This study evaluated the effects of a compound probiotic fermented feed (CPFF) containing Lactobacillus plantarum, Bacillus subtilis, yeast, and Aspergillus niger on rumen in vitro fermentation, in situ feed degradation, and growth performance in beef cattle. Methods: We established a control group (CON) and experimental groups with 2%, 4%, and 8% CPFF supplementation for in vitro fermentation. Results: The results indicated that the NH₃-N concentration in the 4% CPFF group was significantly higher than in the other groups (p < 0.001). Similarly, microbial crude protein (MCP) production was significantly greater in the 4% CPFF group compared to the CON group (p = 0.016). The molar proportions of acetate, butyrate, isobutyrate, and valerate were significantly higher in the 2% and 4% CPFF groups than in the control group (p < 0.001), while propionate levels were significantly lower (p < 0.001). After 48 h, gas production was highest in the 4% CPFF group. Based on improvements in gas production, MCP synthesis, and fermentation intensity, the 4% inclusion level was determined to be optimal for further studies. We conducted an in situ degradation trial using 4% CPFF. Results showed that at 12 h, the neutral detergent fiber (NDF) degradation rate in the 4% CPFF group was significantly higher than in the CON group at 4, 8, 12, and 48 h (p < 0.05). At 48 h, the acid detergent fiber (ADF) degradation rate in the 4% CPFF group was also significantly higher than in the CON group (p < 0.001), and this group exhibited a significant increase in crude protein (CP) degradation (p = 0.030). We analyzed rumen fluid samples from both the CON and 4% CPFF groups after in vitro fermentation using 16S rRNA sequencing and untargeted metabolomics. Microbial community analysis revealed significantly increased abundances of functional bacterial groups such as Rikenellaceae_RC9_gut_group, Christensenellaceae_R-7_group, and UCG-002 in the 4% CPFF group (p < 0.05). Differential metabolites were primarily involved in pathways related to tryptophan metabolism, and tyrosine metabolism signaling. A feeding trial was conducted by adding 4% CPFF to the diet of Angus growing cattle. The results indicated that average daily gain (ADG) (p = 0.004) and average daily feed intake (ADFI) (p = 0.001) were significantly higher in the CPFF group than in the CON group. Conclusions: In conclusion, our results demonstrate that CPFF enhances rumen fermentation activity, optimizes the microbiota and metabolic profiles of rumen fluid, and improves the average daily gain of beef cattle. This research provides a valuable theoretical basis for applying CPFF in beef cattle breeding. Full article

The dissemination of antibiotic resistance genes (ARGs) in riverine ecosystems poses a pressing public health threat, while the mechanisms governing the assembly of the gut resistome in wild fish remain poorly elucidated. This study aimed to elucidate the distributional patterns of ARGs across multiple environmental compartments and to identify factors associated with their variation, particularly the contributions of mobile genetic elements (MGEs) and metal resistance genes (MRGs) to gut resistome variation. Metagenomic sequencing was conducted on 60 samples, comprising water, sediment, and gut contents from three wild fish species (Megalobrama terminalis, Aristichthys nobilis, and Coilia nasus) with distinct feeding habits, collected from four reaches of the Qiantang River basin. A total of 305 ARG subtypes belonging to 23 classes were identified. ARG composition differed significantly across environmental media and host species (permutational multivariate analysis of variance, PERMANOVA; p < 0.01), with host species identity as the primary structuring factor. Variance partitioning analysis (VPA) revealed that MGEs independently explained the largest fraction of ARG variation in A. nobilis (33.8%, p = 0.006), whereas MRGs dominated in C. nasus (33.3%, p = 0.005); in M. terminalis, MGEs and MRGs together accounted for 47.9% of the variation. Metagenomic assembly recovered 2622 ARG-carrying contigs, of which 28.3% (743) were predicted as plasmid sequences; physical co-localization among ARGs, MGEs, and MRGs was detected on both chromosomes and plasmids. Metagenomic binning validated the physical co-localization of ARG-MGE-MRG modules in genera such as Morganella and Burkholderia at the genome level, while plasmid-borne high-risk ARGs were identified in Aeromonas. Risk ranking further revealed significant enrichment of Rank II potentially high-risk ARGs (e.g., mcr-7.1, blaZ) in fish guts, carried by potential pathogens. These findings suggest that horizontal gene transfer involving MGEs and co-selection related to MRGs are closely associated with the fish gut resistome composition in a manner dependent on host ecology, providing a scientific basis for shifting riverine resistance management from concentration-based control toward the interruption of dissemination pathways. Full article